Xylanase variants and polynucleotides encoding the same

Abstract

The present invention relates to xylanase variants of a parent xylanase having increased thermostability compared to the parent xylanase. The present invention also relates to polynucleotides encoding these variants, nucleic acid constructs, vectors and host cells comprising these polynucleotides, and methods for producing the variants of the present invention.

Description

[0001] References to sequence listings

[0002] This application contains a Sequence Listing in computer readable form, which is incorporated herein by reference. Technical Field

[0003] The present invention relates to polypeptides having xylanase activity and polynucleotides encoding these polypeptides. The present invention also relates to nucleic acid constructs, vectors, and host cells comprising these polynucleotides, as well as methods of producing and using these polypeptides. The present invention also relates to compositions comprising the polypeptides of the present invention and the use of the polypeptides of the present invention to increase starch and / or gluten yield in corn kernels during wet milling. Background Art

[0004] Conventional corn wet milling is a process designed for the recovery and purification of starch and several by-products, including germ, gluten (protein), and fiber. Fiber is the least valuable by-product, so the industry has invested a lot of effort to increase the yield of more valuable products, such as starch and gluten, while reducing the fiber fraction. High-quality starch is valuable because it can be used for a variety of commercial purposes after further processing into products such as dried starch, modified starch, dextrins, sweeteners, and alcohol. Gluten is commonly used in animal feed, such as corn gluten meal (about 60% protein) or corn gluten feed (about 20% protein).

[0005] The wet milling process can vary significantly depending on the specific milling equipment used, but generally the process includes grain cleaning, steeping, milling, germ separation, secondary milling, fiber separation, gluten separation, and starch separation. After cleaning the corn kernels, they are typically softened by soaking in water or in a dilute SO2 solution under controlled time and temperature conditions. The kernels are then milled to break down the pericarp and separate the germ from the rest of the kernel. The remaining slurry, consisting primarily of fiber, starch, and gluten, is finely milled and screened in a fiber washing process to separate the fiber from the starch and gluten, and the gluten and starch are then separated, and the starch can be purified in a washing / filtration process.

[0006] It has been suggested to use enzymes in several steps of the wet milling process, for example using enzymes in the impregnation step of the wet milling process. It has been shown that commercial enzyme products (available from Novozymes A / S) is suitable for the first step of the wet milling process, a steeping step in which the corn kernels are soaked in water.

[0007] Recently, "enzymatic milling," a modified wet milling process that uses proteases to significantly reduce overall processing time during corn wet milling and eliminate the need for sulfur dioxide as a processing agent, has been developed. Johnston et al., Cereal Chem, 81, pp. 626-632 (2004).

[0008] US 6,566,125 discloses a method for obtaining starch from maize, the method involving soaking maize kernels in water to produce soaked maize kernels, milling the soaked maize kernels to produce a milled maize slurry, and incubating the milled maize slurry with an enzyme (eg, a protease).

[0009] US 5,066,218 discloses a method of grinding cereals, particularly corn, which comprises cleaning the cereals, soaking the cereals in water to soften them, and then grinding the cereals with cellulase.

[0010] WO 2002 / 000731 discloses a process for treating crop seeds, which comprises soaking the seeds in water for 1-12 hours, wet milling the soaked seeds, and treating the seeds with one or more enzymes, including an acid protease.

[0011] WO 2002 / 000911 discloses a process for starch gluten separation which comprises subjecting ground starch to an acid protease.

[0012] WO 2002 / 002644 discloses a process for washing a starch slurry obtained from the starch gluten separation step of a milling process, which process comprises washing the starch slurry with an aqueous solution comprising an effective amount of an acid protease.

[0013] WO 2014 / 082566 and WO 2014 / 082564 disclose cellulolytic compositions for use in wet milling.

[0014] Although the effects of using enzymes in corn wet milling have been studied in the art, there remains a need for improved enzyme technology during steeping / soaking of the corn kernel, during milling of the corn kernel, and during starch and gluten separation that can reduce the energy expenditure and costs associated with corn wet milling and provide increased starch and gluten yields.

[0015] WO 2016 / 005522 discloses a GH5 xylanase gene isolated from Chryseobacterium sp-10696 as SEQ ID NO: 25 and the encoded polypeptide as SEQ ID NO: 26.

[0016] WO 2019 / 023222 discloses a method for increasing the total starch yield and / or gluten yield obtainable from corn kernels in a wet milling process, the method comprising mixing the corn kernels or fractions of the corn kernels with an enzyme composition comprising an effective amount of one or more hydrolases, wherein at least one of the hydrolases is selected from the group consisting of a GH30 polypeptide, a GH5 polypeptide, and combinations thereof.

[0017] The present invention provides xylanase variants having improved properties compared to their parent. Summary of the Invention

[0018] The present invention provides xylanase variants having improved properties compared to a parent xylanase.

[0019] The present invention relates to xylanase variants of a parent xylanase, comprising a substitution at one or more positions corresponding to positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1, and wherein the variant has xylanase activity, and wherein the xylanase variant has increased thermostability compared to the xylanase of SEQ ID NO: 1.

[0020] The present invention also relates to xylanase variants of a parent xylanase, wherein the variant further comprises a substitution at one or more positions corresponding to positions 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375 66, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530 and 540, and wherein the variants are identical to SEQ The invention also provides a polypeptide having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1, and wherein the variant has xylanase activity, and wherein the xylanase variant has increased thermostability compared to the xylanase of SEQ ID NO: 1.

[0021] The present invention also relates to compositions comprising the xylanase variants of the present invention.

[0022] The present invention also relates to polynucleotides encoding the variants according to the present invention, nucleic acid constructs comprising the polynucleotides encoding the variants according to the present invention, expression vectors comprising the polynucleotides encoding the variants according to the present invention, and host cells comprising the polynucleotides encoding the variants according to the present invention.

[0023] The present invention also relates to methods of producing a xylanase variant, the method comprising (a) cultivating a host cell of the present invention under conditions suitable for expression of the variant; and (b) recovering the variant.

[0024] The present invention further relates to a method for obtaining a xylanase variant of a parent xylanase, the method comprising the step of introducing a substitution at one or more positions corresponding to positions 45, 149, 364, 258, 276 and 388 of SEQ ID NO: 1, the method thereby providing a xylanase variant of the parent xylanase, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to the amino acid sequence of the polypeptide of SEQ ID No: 1. Compared to the xylanase of NO: 1, the xylanase variant has increased thermostability.

[0025] The present invention also relates to a method for increasing the starch yield and / or gluten yield of corn kernels in a wet milling process, the method comprising contacting the corn kernels or fractions of the corn kernels, particularly the fiber-enriched fractions, with an effective amount of a xylanase variant of the present invention and optionally one or more hydrolases.

[0026] The present invention also relates to processes for producing fermentation products, such as ethanol, from starch-containing material or cellulose-containing material using a fermenting organism.

[0027] The present invention also relates to enzyme blends or compositions comprising at least one or more xylanase variants of the present invention.

[0028] The present invention also relates to recombinant host cells comprising a heterologous polynucleotide encoding at least one or more xylanase variants of the present invention.

[0029] The present invention also relates to compositions (e.g., fermenting or fermented mash compositions) comprising: (i) a recombinant host cell or fermenting organism comprising a heterologous polynucleotide encoding an α-amylase and / or a protease and at least one or more xylanase variants of the present invention.

[0030] definition

[0031] In light of this detailed description, the following definitions apply. Note that the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0032] Reference herein to "about" a value or parameter includes aspects directed to the value or parameter itself. For example, description referring to "about X" includes the aspect "X."

[0033] Unless defined otherwise or clearly indicated by the context, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0034] Allelic variant: The term "allelic variant" means any of two or more alternative forms of a gene occupying the same chromosomal locus. Allelic variation arises naturally through mutation and can lead to polymorphism within a population. Gene mutations can be silent (no change in the encoded polypeptide) or can encode a polypeptide with an altered amino acid sequence. An allelic variant of a polypeptide is a polypeptide encoded by an allelic variant of a gene.

[0035] Amino acid: As used herein, the term "amino acid" refers to the standard twenty genetically encoded amino acids and their corresponding stereoisomers in the "d" form (as compared to the natural "l" form), ω-amino acids, other naturally occurring amino acids, unconventional amino acids (e.g., α,α-disubstituted amino acids, N-alkyl amino acids, etc.), and chemically derivatized amino acids. Chemical derivatives of one or more amino acids can be achieved by reaction with functional side groups. Such derivatized molecules include, for example, those in which the free amino group has been derivatized to form an amine hydrochloride, a p-toluenesulfonyl group, a carboxyphenoxy group, a tert-butoxycarbonyl group, a chloroacetyl group, or a formyl group. Free carboxyl groups can be derivatized to form salts, methyl and ethyl esters or other types of esters and hydrazides. Free hydroxyl groups can be derivatized to form O-acyl or O-alkyl derivatives. Also included as chemical derivatives are peptides containing naturally occurring amino acid derivatives of the twenty standard amino acids. For example, 4-hydroxyproline can be substituted for proline; 5-hydroxylysine can be substituted for lysine; 3-methylhistidine can be substituted for histidine; homoserine can be substituted for serine, and ornithine can be substituted for lysine. Derivatives also include peptides containing one or more additions or deletions, as long as the necessary activity is maintained. Other modifications include amidation, amino-terminal acylation (e.g., acetylation or thioglycolic acid amidation), terminal carboxyl amidation (e.g., with ammonia or methylamine), and similar terminal modifications.

[0036] When an amino acid is explicitly listed, such as "alanine" or "Ala" or "A," the term refers to both l-alanine and d-alanine, unless expressly stated otherwise. Other unconventional amino acids may also be suitable components of the polypeptides of the present invention, as long as the desired functional properties are retained by the polypeptide. For the peptides shown, each encoded amino acid residue is represented by a single-letter designation, corresponding to the common name of the conventional amino acid, where appropriate. In one embodiment, the polypeptides of the present invention comprise or consist of l-amino acids.

[0037] Arabinofuranosidase / polypeptide with arabinofuranosidase activity: The term "arabinofuranosidase" refers to an α-L-arabinofuranoside arabinofuranohydrolase (EC 3.2.1.55), which catalyzes the hydrolysis of terminal non-reducing α-L-arabinofuranoside residues in α-L-arabinosides. The enzyme acts on α-L-arabinofuranosides, α-L-arabinans containing (1,3)- and / or (1,2)- and / or (1,5)-linkages, arabinoxylans, and arabinogalactans. α-L-arabinofuranosidase is also known as arabinosidase, α-arabinosidase, α-L-arabinosidase, α-arabinofuranosidase, polysaccharide α-L-arabinofuranosidase, α-L-arabinofuranoside hydrolase, L-arabinosidase, or α-L-arabinanase. Medium viscosity wheat arabinoxylan (Megazyme International Ireland, Ltd., Bray, Co., Wicklow, Ireland) can be used in a total volume of 200 μl at 40°C for 30 minutes, followed by Arabinofuranosidase activity is determined by arabinose analysis using HPX-87H column chromatography (Bio-Rad Laboratories, Inc., Hercules, CA, USA). Arabinofuranosidases can be found, for example, in the GH43, GH62, and GH51 families according to Henrissat, 1991, A classification of glycosyl hydrolases based on amino-acid sequences similarities, Biochem. J. 280:309-316, and Henrissat and Bairoch, 1996, Updating the sequence-based classification of glycosyl hydrolases, Biochem. J. 316:695-696.

[0038] β-glucosidase / polypeptide with β-glucosidase activity: The term "β-glucosidase" means a β-D-glucoside glucohydrolase (EC 3.2.1.21) that catalyzes the hydrolysis of terminal non-reducing β-D-glucose residues and releases β-D-glucose. β-glucosidase activity can be determined according to the procedure of Venturi et al., 2002, J. Basic Microbiol. 42:55-66 using p-nitrophenyl-β-D-pyranoside as a substrate. One unit of β-glucosidase is defined as the activity of β-glucosidase at 25°C, pH 4.8 in a solution containing 0.01% 20% of 50 mM sodium citrate produces 1.0 micromole of p-nitrophenolate anion per minute from 1 mM p-nitrophenyl-β-D-pyranoglucopyranoside as a substrate.

[0039] β-Xylosidase / polypeptide with β-xylosidase activity: The term "β-xylosidase" means β-D-xyloside xylohydrolase (EC 3.2.1.37), which catalyzes the exohydrolysis of short β(1→4)-xylo-oligosaccharides to remove consecutive D-xylose residues from the non-reducing end. β-Xylosidase activity was determined in 100 mM sodium citrate at pH 5 at 40°C using 1 mM p-nitrophenyl-β-D-xyloside as substrate. One unit of β-Xylosidase was defined as the activity of 1 mM p-nitrophenyl-β-D-xyloside at 40°C at pH 5 in a 100 mM sodium citrate solution containing 0.01% 20% of 100 mM sodium citrate produces 1.0 micromole of p-nitrophenolate anion per minute from 1 mM p-nitrophenyl-β-D-xyloside.

[0040] Cellobiohydrolase / polypeptide with cellobiohydrolase activity: The term "cellobiohydrolase" means 1,4-β-D-glucan cellobiohydrolase (EC 3.2.1.91 and EC 3.2.1.176) which catalyzes the hydrolysis of 1,4-β-D-glycosidic linkages in cellulose, cellooligosaccharides, or any polymer containing β-1,4-linked glucose, releasing cellobiose from either the reducing (cellobiohydrolase I) or non-reducing (cellobiohydrolase II) ends of the chain (Teeri, 1997, Trends in Biotechnology 15:160-167; Teeri et al., 1998, Biochem. Soc. Trans. 26:173-178). Cellobiohydrolase activity can be determined according to the procedures described by Lever et al., 1972, Anal. Biochem. 47:273-279; van Tilbeurgh et al., 1982, FEBS Letters 149:152-156; van Tilbeurgh and Claeyssens, 1985, FEBS Letters 187:283-288; and Tomme et al., 1988, Eur. J. Biochem. 170:575-581.

[0041] Contact Time: For one or more enzymes to react with a substrate, the one or more enzymes must be in contact with the substrate. "Contact time" refers to the period of time during which an effective amount of one or more enzymes is in contact with at least a portion of the substrate material. During the contact time, the enzyme may not be in contact with all of the substrate material; however, mixing the one or more enzymes with the substrate material allows for the potential for enzyme-catalyzed hydrolysis of a portion of the substrate material during the contact time.

[0042] Cellulolytic enzymes or cellulase / polypeptides having cellulase activity or cellulolytic activity: The terms "cellulolytic enzyme," "cellulase," and polypeptides having cellulase activity or cellulolytic activity are used interchangeably herein and refer to one or more (e.g., several) enzymes that hydrolyze a cellulosic material, including any material containing cellulose (e.g., fiber). Cellulolytic enzymes include one or more endoglucanases (EC 3.2.1.4), one or more cellobiohydrolases (EC 3.2.1.91 and EC 3.2.1.150), one or more beta-glucosidases (EC 3.2.1.21), or a combination thereof. Two basic methods for measuring cellulolytic enzyme activity include: (1) measuring total cellulolytic enzyme activity, and (2) measuring individual cellulolytic enzyme activities (endoglucanase, cellobiohydrolase, and beta-glucosidase), as described in Zhang et al., 2006, Biotechnology Advances 24:452-481. Total cellulolytic enzyme activity can be measured using insoluble substrates including Whatman No. 1 filter paper, microcrystalline cellulose, bacterial cellulose, algal cellulose, cotton, pretreated lignocellulose, etc. The most common assay for total cellulolytic activity is the filter paper assay using Whatman No. 1 filter paper as the substrate. This assay was established by the International Union of Pure and Applied Chemistry (IUPAC) (Ghose, 1987, Pure Appl. Chem. 59:257-68).

[0043] Cellulolytic enzyme activity can also be determined by measuring the increase in sugar production / release during hydrolysis of a cellulosic material by one or more cellulolytic enzymes under the following conditions: 1-50 mg cellulolytic enzyme protein / g cellulose in pretreated corn stover (PCS) (or other pretreated cellulosic material) at a suitable temperature (e.g., 40°C-80°C, e.g., 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, or 80°C) and at a suitable pH (e.g., 4-9, e.g., 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, or 9.0) for 3-7 days, compared to a control hydrolysis to which no cellulolytic enzyme protein is added. Typical conditions were: 1 ml reaction, washed or unwashed PCS, 5% insoluble solids (dry weight), 50 mM sodium acetate 5 (pH 5), 1 mM MnSO4, 50°C, 55°C, or 60°C, 72 hours, by Sugar analysis was performed using HPX-87H column chromatography (Bio-Rad Laboratories, Inc., Hercules, CA, USA).

[0044] Corn kernels: Many varieties of corn kernels are known, including, for example, dent corn, flint corn, lemma corn, striped corn, sweet corn, waxy corn, and the like. Some corn kernels have an outer covering called a "pericarp" that protects the germ within the kernel. It repels water and water vapor and is undesirable to insects and microorganisms. The only area of ​​the kernel not covered by the "pericarp" is the "tip cap," which is the point of attachment of the kernel to the cob.

[0045] Corn kernel or fraction of corn kernel: This term is used to describe corn kernels that have been subjected to the wet milling process. When the corn kernels are broken down and processed, all fractionated portions of the corn kernels are considered to be included when using this term. This term includes, for example, soaked kernels, ground kernels, corn kernel material, a first fraction, a second fraction, one or more fractions of corn kernel material, etc.

[0046] Corn kernel material: preferably used to refer to a material comprising fiber, gluten, and starch, preferably obtained by steaming and grinding the crop kernels and separating the material comprising fiber, gluten, and starch from the germ. As the corn kernel material moves through the fiber wash, it is separated into several fractions, including a first fraction (s) and a second fraction (f). Thus, "fractions of corn kernel material" and "one or more fractions of corn kernel material" refer specifically to these first fraction (s) and second fraction (f).

[0047] cDNA: The term "cDNA" refers to a DNA molecule that can be prepared by reverse transcription from a mature, spliced ​​mRNA molecule obtained from a eukaryotic or prokaryotic cell. cDNA lacks intron sequences that may be present in the corresponding genomic DNA. The initial, primary RNA transcript is a precursor to mRNA that is processed through a series of steps, including splicing, before appearing as mature, spliced ​​mRNA.

[0048] Coding sequence: The term "coding sequence" means a polynucleotide that directly specifies the amino acid sequence of a polypeptide. The boundaries of the coding sequence are generally determined by an open reading frame, which begins with a start codon (e.g., ATG, GTG, or TTG) and ends with a stop codon (e.g., TAA, TAG, or TGA). The coding sequence can be genomic DNA, cDNA, synthetic DNA, or a combination thereof.

[0049] Control sequences: The term "control sequences" means nucleic acid sequences necessary for the expression of a polynucleotide encoding a mature polypeptide of the present invention. Each control sequence may be native (i.e., from the same gene) or exogenous (i.e., from a different gene) to the polynucleotide encoding the polypeptide, or native or exogenous to each other. Such control sequences include, but are not limited to, a leader sequence, a polyadenylation sequence, a propeptide sequence, a promoter, a signal peptide sequence, and a transcription terminator. At a minimum, a control sequence includes a promoter, and transcription and translation termination signals. These control sequences may be provided with a plurality of linkers for the purpose of introducing specific restriction sites that facilitate connection of the control sequence to the coding region of the polynucleotide encoding the polypeptide.

[0050] Corresponding to: As used herein, the term "corresponding to" refers to a manner of determining a specific amino acid in a sequence where a specific amino acid sequence is referenced. For example, for the purposes of the present invention, when reference is made to a specific amino acid position, a skilled artisan can align another amino acid sequence with the referenced amino acid sequence to determine which specific amino acid may be of interest in the other amino acid sequence. Alignment of another amino acid sequence with, for example, the sequence set forth in SEQ ID NO: 1 or any other sequence listed herein has been described elsewhere herein. Alternative alignment methods may be used and are well known to those skilled in the art.

[0051] Expression: The term "expression" includes any step involved in the production of the polypeptide including, but not limited to, transcription, post-transcriptional modification, translation, post-translational modification, and secretion.

[0052] Expression vector: The term "expression vector" means a linear or circular DNA molecule that contains a polynucleotide encoding a polypeptide and is operably linked to control sequences that provide for its expression.

[0053] Endoglucanase: The term "endoglucanase" means an endo-1,4-(1,3;1,4)-β-D-glucan 4-glucanohydrolase (EC 3.2.1.4) that catalyzes the endohydrolysis of 1,4-β-D-glucosidic bonds in cellulose, cellulose derivatives (such as carboxymethylcellulose and hydroxyethylcellulose), lichenin, mixed β-1,3 glucans such as cereal β-D-glucans or xyloglucans, and β-1,4 bonds in other plant materials containing cellulose components. Endoglucanase activity can be determined by measuring a decrease in substrate viscosity or an increase in reducing ends as determined by a reducing sugar assay (Zhang et al., 2006, Biotechnology Advances 24:452-481). For the purposes of the present invention, endoglucanase activity is determined according to the procedure of Ghose, 1987, Pure and Appl. Chem 59: 257-268, at pH 5, 40°C, using carboxymethylcellulose (CMC) as substrate.

[0054] Family 61 glycoside hydrolase: The term "Family 61 glycoside hydrolase" or "Family GH61" or "GH61" means a polypeptide belonging to glycoside hydrolase family 61 according to Henrissat, 1991, A classification of glycosyl hydrolases based on amino-acid sequence similarities, Biochem. J. 280:309-316, and Henrissat and Bairoch, 1996, Updating the sequence-based classification of glycosyl hydrolases, Biochem. J. 316:695-696. The enzymes in this family were originally classified as a glycoside hydrolase family based on measurement of very weak endo-1,4-β-D-glucanase activity in one family member. The structure and mode of action of these enzymes are irregular, and they can not be regarded as real glycosidases.However, based on their ability to enhance lignocellulose decomposition when used in combination with a mixture of cellulase or cellulase, they are retained in CAZy classification. GH61 polypeptides have recently been classified as soluble polysaccharide monooxygenases (Quinlan et al., 2011, Proc.Natl.Acad.Sci.USA [Proceedings of the National Academy of Sciences of the United States] 208: 15079-15084; Phillips et al., 2011, ACS Chem.Biol. [ACS Chemical Biology] 6: 1399-1406; Lin et al., 2012, Structure [Structure] 20: 1051-1061), and named as " auxiliary activity 9 " or " AA9 " polypeptide.

[0055] Fragment: The term "fragment" means a polypeptide having one or more (eg, several) amino acids deleted from the amino and / or carboxyl terminus of the mature polypeptide, wherein the fragment has xylanase activity.

[0056] Germ: The "germ" is the only living part of the corn kernel. It contains the genetic information, enzymes, vitamins, and minerals necessary for the kernel to grow into a corn plant. In yellow dent corn, about 25% of the germ is corn oil. The endosperm, which is covered or surrounded by the germ, contains about 82% of the kernel's dry weight and is the source of energy (starch) and protein for seed germination. There are two types of endosperm, soft endosperm and hard endosperm. In hard endosperm, the starch is tightly packed together. In soft endosperm, the starch is loose.

[0057] GH5 polypeptide: refers to a polypeptide with enzymatic activity, which is classified as a member of glycoside hydrolase family 5 in the carbohydrate-active enzyme (CAZyme) database ( http: / / www.cazy.org / ).

[0058] GH8 polypeptide: refers to a polypeptide with enzymatic activity, which is classified as a member of glycoside hydrolase family 8 in the carbohydrate-active enzyme (CAZyme) database ( http: / / www.cazy.org / ).

[0059] GH10 polypeptide: refers to a polypeptide with enzymatic activity. http: / / www.cazy.org / It is classified as a member of glycoside hydrolase family 10 in the Carbohydrate Active Enzymes (CAZyme) database available on [1]. (Lombard, V.; Golaconda Ramulu, H.; Drula, E.; Coutinho, PM; Henrissat, B. (21 November 2013). “The carbohydrate-active enzymes database (CAZy) in 2013”. Nucleic Acids Research. 42(D1):D490-D495; Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, Henrissat B (January 2009). “The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics”. Nucleic Acids Res. 37(Database issue):D233-8).

[0060] The GH11 polypeptide refers to a polypeptide having enzymatic activity, which is classified as a member of glycoside hydrolase family 11 in the carbohydrate-active enzyme (CAZyme) database.

[0061] GH30 polypeptide: refers to a polypeptide with enzymatic activity, which is classified as a member of glycoside hydrolase family 30 in the carbohydrate-active enzyme (CAZyme) database ( http: / / www.cazy.org / ).

[0062] GH62 polypeptide: refers to a polypeptide having enzymatic activity, which is classified as a member of glycoside hydrolase family 62 in the carbohydrate-active enzyme (CAZyme) database.

[0063] GH43 polypeptide: refers to a polypeptide having enzymatic activity, which is classified as a member of glycoside hydrolase family 43 in the carbohydrate-active enzyme (CAZyme) database.

[0064] GH51 polypeptide: refers to a polypeptide having enzymatic activity, which is classified as a member of glycoside hydrolase family 51 in the carbohydrate-active enzyme (CAZyme) database.

[0065] Gluten: Gluten is a protein composed of two smaller proteins, glutenin and gliadin. "Gluten" herein refers to the majority of the protein found in corn kernels. The main products of gluten from corn wet milling are corn gluten meal (about 60% protein) and corn gluten feed (about 20% protein).

[0066] Grinding (grind or grinding): The term "grinding" refers to breaking down the corn kernels into smaller components.

[0067] Host cell: The term "host cell" means any cell type that is susceptible to transformation, transfection, transduction, etc. with a nucleic acid construct or expression vector comprising a polynucleotide of the present invention. The term "host cell" encompasses any progeny of a parent cell that is not identical to the parent cell due to mutations that occur during replication.

[0068] Highly branched xylans: The term "highly branched xylans" means that more than 50% of the xylosyl units in the arabinoxylan backbone are substituted. This is preferably calculated from linkage analysis as performed in Huismann et al. Carbohydrate Polymers, 2000, 42: 269-279.

[0069] Hydrolytic enzyme or hydrolase / polypeptide with hydrolase activity: "Hydrolase" and polypeptide with hydrolase activity are used interchangeably herein and refer to any catalytic protein that uses water to break down a substrate. Hydrolases include cellulases (EC 3.2.1.4), xylanases (EC 3.2.1.8), arabinofuranosidases (EC 3.2.1.55 (non-reducing end α-L-arabinofuranosidase); EC 3.2.1.185 (non-reducing end β-L-arabinofuranosidase), cellobiohydrolase I (EC 3.2.1.150), cellobiohydrolase II (EC 3.2.1.91), cellobiosidase (EC 3.2.1.176), β-glucosidase (EC 3.2.1.21), β-xylosidase (EC 3.2.1.37).

[0070] Isolated: The term "isolated" means a substance that is in a form or setting not found in nature. Non-limiting examples of isolated substances include (1) any non-naturally occurring substance, (2) any substance, including but not limited to any enzyme, variant, nucleic acid, protein, peptide, or cofactor, that is at least partially removed from one or more or all of the naturally occurring components associated with its properties; (3) any substance that has been modified by the hand of man relative to the substance found in nature; or (4) any substance that has been modified by increasing the amount of the substance relative to other components with which it is naturally associated (e.g., recombinant production in a host cell; multiple copies of a gene encoding the substance; and use of a stronger promoter than the promoter naturally associated with the gene encoding the substance).

[0071] Incubation time: The time that one or more fractions of corn kernel material are contacted with the hydrolytic enzyme during fiber washing without being screened.

[0072] In many preferred embodiments, the methods according to the present invention utilize a system comprising a space (V) or "incubator" within which the material is "left to be affected" by the enzyme, and in such cases, the incubation time can be determined by:

[0073]

[0074] Alternatively, if the flow into the incubator is expressed as volume per time unit:

[0075]

[0076] Grinding Equipment: "Grinding Equipment" refers to all equipment used on a mill. The wet grinding process will vary depending on the available grinding equipment. Examples of grinding equipment include impregnation tanks, evaporators, screw presses, rotary dryers, dewatering screens, centrifuges, hydrocyclones, etc. The size and number of individual grinding equipment / grinding lines can vary on different mills, which will affect the grinding process. For example, the number of fiber washing screen units can vary, as can the size of the centrifuge.

[0077] Nucleic acid construct: The term "nucleic acid construct" means a single-stranded or double-stranded nucleic acid molecule that is isolated from a naturally occurring gene or modified to contain a nucleic acid segment in a manner not originally found in nature, or is synthetic, and that contains one or more control sequences.

[0078] Operably linked: The term "operably linked" means a configuration in which a control sequence is placed at an appropriate position relative to the coding sequence of a polynucleotide such that the control sequence directs the expression of the coding sequence.

[0079] Parent or parent xylanase: As used herein, the term "parent" xylanase refers to the xylanase that was modified to produce the variant xylanase of the present invention. The term also refers to the polypeptide to which the variant of the present invention is compared. The parent can be a naturally occurring (wild-type) polypeptide, or it can even be a variant thereof prepared by any suitable means. For example, the parent protein can be a variant of a naturally occurring polypeptide that has been modified or altered in its amino acid sequence. Thus, the parent xylanase can have one or more (or one or several) amino acid substitutions, deletions, and / or insertions. Thus, the parent xylanase can be a variant of the parent xylanase. The parent can also be an allelic variant, which is a polypeptide encoded by any of two or more alternative forms of a gene occupying the same chromosomal locus. As used herein, the term "parent" or "parent xylanase" refers to the xylanase of SEQ ID NO: 1 or any xylanase having at least 60% sequence identity to SEQ ID NO: 1. The parent xylanase can also be a polypeptide comprising a fragment of SEQ ID NO: 1.

[0080] Retention Time: The time allowed for one or more hydrolytic enzymes to react with the corn kernel or fraction of corn kernel during a fiber washing process.

[0081] In some embodiments, the retention time is the period of time that the corn kernel material and one or more fractions thereof received in the first screen unit (S1) are contacted with an effective amount of one or more hydrolytic enzymes before leaving the fiber washing system again. During the retention time, the one or more fractions of the corn kernel material are incubated with the one or more hydrolytic enzymes in the space (V) and then leave the fiber washing system as part of the first fraction (s1) from the most upstream screen unit (S1) or as part of the second fraction (f4) from the most downstream screen unit (S4).

[0082] Retention time can preferably be estimated as the average duration that the solids spend in the fiber washing system as defined in the present invention. This can be estimated by the following relationship:

[0083]

[0084] Alternatively, if the inflow to the system is expressed in volume per time unit:

[0085]

[0086] The volume of the system is typically set equal to the sum of the volumes of all voids in the system; however, since the pipes in the system are typically made very small, it may be preferable to ignore the volume of the pipes.

[0087] Screened: The term "screened" or "screening" refers to the process of separating corn kernel material into a first fraction s and a second fraction f and moving these fractions from one screening unit to another. The non-screening period is a non-separation period provided for incubating the corn kernel material or its fractions with the enzyme.

[0088] Sequence identity: The relatedness between two amino acid sequences or between two nucleotide sequences is described by the parameter "sequence identity".

[0089] For the purposes of the present invention, the degree of sequence identity between two amino acid sequences is determined using the Needleman-Wunsch algorithm (Needleman and Wunsch, 1970, J. Mol. Biol. 48: 443-453) as implemented in the Needle program of the EMBOSS package (EMBOSS: The European Molecular Biology Open Software Suite, Rice et al., 2000, Trends Genet. 16: 276-277), preferably version 3.0.0 or later. Version 6.1.0 is used.

[0090] The optional parameters used are gap opening penalty 10, gap extension penalty 0.5 and EBLOSUM62 (EMBOSS version of BLOSUM62) substitution matrix. The output of Needle (obtained using the non-simplified option) labeled as "longest identity" is used as identity percentage and is calculated as follows: (identical residue x 100) / (total number of gaps in the alignment length-alignment).

[0091] Starch: The term "starch" means a complex polysaccharide composed of glucose units found in plants in the form of storage granules, consisting of amylose and amylopectin and expressed as (C6H 10 O5)n (where n is any number) of any material.

[0092] Impregnation or soaking: The term "impregnation" means soaking with water and optionally SO 2 Soak crop kernels.

[0093] Wild-type enzyme: The term "wild-type" xylanase refers to a xylanase expressed by a naturally occurring microorganism found in nature, such as bacteria, yeast, or filamentous fungi. When the parent enzyme is not a variant enzyme, the terms "wild-type enzyme" and "parent enzyme" are used interchangeably.

[0094] Variant: The term "variant" means a polypeptide having xylanase activity that comprises an alteration (i.e., a substitution, insertion, and / or deletion of one or more (several) amino acid residues) at one or more (several) positions. A substitution means replacing the amino acid occupying a position with a different amino acid; a deletion means removing the amino acid occupying a position; and an insertion means adding an amino acid adjacent to and immediately following the amino acid occupying a position. Variants of the invention may have at least 20%, such as at least 40%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the xylanase of the polypeptide of SEQ ID NO: 1.

[0095] Xylanase / polypeptide having xylanase activity: The terms "xylanase" and polypeptide having xylanase activity are used interchangeably herein and refer to 1,4-β-D-xylan-xylose hydrolase (EC 3.2.1.8) that catalyzes the endohydrolysis of 1,4-β-D-xylosidic bonds in xylans. Xylanase activity can be detected at 0.01% at 37°C. The activity was determined using 0.2% AZCL-arabinoxylan as a substrate in 200 mM sodium phosphate (pH 6) and X-100. One unit of xylanase activity is defined as the amount of xylanase activity that produces 1.0 micromole of azurin per minute in 200 mM sodium phosphate (pH 6) at 37°C and pH 6 from 0.2% AZCL-arabinoxylan as a substrate.

[0096] Nomenclature

[0097] For the purposes of the present invention, the nomenclature [Y / F] means that the amino acid at this position can be tyrosine (Try, Y) or phenylalanine (Phe, F). Similarly, the nomenclature [V / G / A / I] means that the amino acid at this position can be valine (Val, V), glycine (Gly, G), alanine (Ala, A), or isoleucine (Ile, I), and so on for other combinations as described herein. Unless otherwise indicated, amino acid X is defined such that it can be any of the 20 naturally occurring amino acids.

[0098] Variant naming conventions

[0099] For the purposes of the present invention, SEQ ID NO: 1 is used to determine the corresponding amino acid residue in another xylanase. The amino acid sequence of the other xylanase is aligned with SEQ ID NO: 1, and based on the alignment, the amino acid position number corresponding to any amino acid residue in SEQ ID NO: 1 is determined using the Needleman-Wunsch algorithm (Needleman and Wunsch, 1970, J. Mol. Biol. 48: 443-453) as implemented in the Needle program of the EMBOSS package (EMBOSS: European Molecular Biology Open Software Suite, Rice et al., 2000, Trends Genet. 16: 276-277) (e.g., version 5.0.0 or later). The parameters used are a gap opening penalty of 10, a gap extension penalty of 0.5, and the EBLOSUM62 (EMBOSS version of BLOSUM62) substitution matrix.

[0100] The identity of the corresponding amino acid residue in another xylanase can be determined by aligning multiple polypeptide sequences using several computer programs, including but not limited to MUSCLE (Multiple Sequence Comparison by Log-Expectation; Version 3.5 or later; Edgar, 2004, Nucleic Acids Research 32:1792-1794), MAFFT (Version 6.857 or later; Katoh and Kuma, 2002, Nucleic Acids Research 30:3059-3066; Katoh et al., 2005, Nucleic Acids Research 33:511-518; Katoh and Toh, 2007, Bioinformatics 23:372-374; Katoh et al., 2009, Methods in Molecular Biology, 1994). Biology 537:39-64; Katoh and Toh, 2010, Bioinformatics 26:1899-1900) and EMBOSS EMMA (version 1.83 or later; Thompson et al., 1994, Nucleic Acids Research 22:4673-4680) using ClustalW.

[0101] When other enzymes deviate from the polypeptide of SEQ ID NO: 1 such that traditional sequence-based comparison methods cannot detect their relationship (Lindahl and Elofsson, 2000, J. Mol. Biol. 295: 613-615), other pairwise sequence comparison algorithms can be used. Higher sensitivity in sequence-based searches can be obtained using search programs that use probabilistic representations (profiles) of families of polypeptides to search databases. For example, the PSI-BLAST program generates multiple profiles through an iterative database search process and is capable of detecting distant homologs (Atschul et al., 1997, Nucleic Acids Res. 25: 3389-3402). Even higher sensitivity can be achieved if the family or superfamily of polypeptides has one or more representatives in the protein structure database. Programs such as GenTHREADER (Jones, 1999, J. Mol. Biol. 287:797-815; McGuffin and Jones, 2003, Bioinformatics 19:874-881) use information from a variety of sources (PSI-BLAST, secondary structure predictions, structural alignment profiles, and solvation potential) as input to a neural network that predicts the structural fold of a query sequence. Similarly, the method of Gough et al., 2000, J. Mol. Biol. 313:903-919 can be used to align sequences of unknown structure with superfamily models present in the SCOP database. These alignments can, in turn, be used to generate homology models for polypeptides, and the accuracy of such models can be assessed using a variety of tools developed for this purpose.

[0102] For proteins of known structure, several tools and resources can be used to retrieve and generate structural alignments. For example, the SCOP superfamily of proteins has been structurally aligned, and those alignments are accessible and downloadable. Multiple algorithms such as distance alignment matrices (Holm and Sander, 1998, Proteins [protein] 33:88-96) or combined extensions (Shindyalov and Bourne, 1998, Protein Engineering [protein engineering] 11:739-747) can be used to compare two or more protein structures, and the implementation of these algorithms can be used in addition to query structural databases with target structures to find possible structural homologues (e.g., Holm and Park, 2000, Bioinformatics [biological information science] 16:566-567).

[0103] In describing the variants of the present invention, the nomenclature described below has been adapted for ease of reference. Accepted IUPAC single-letter or three-letter amino acid abbreviations are used.

[0104] replace For amino acid substitutions, the following nomenclature is used: original amino acid, position, substituted amino acid. Accordingly, the substitution of threonine at position 226 by alanine is represented as "Thr226Ala" or "T226A." Multiple mutations are separated by a plus sign ("+"), for example, "Gly205Arg+Ser411Phe" or "G205R+S411F" represents the substitution of glycine (G) at position 205 and serine (S) at position 411 by arginine (R) and phenylalanine (F), respectively.

[0105] Missing For amino acid deletions, the following nomenclature is used: original amino acid, position, * Accordingly, the deletion of glycine at position 195 is indicated as "Gly195*" or "G195*". Multiple deletions are separated by plus signs ("+"), for example, "Gly195*+Ser411*" or "G195*+S411*".

[0106] insert. For amino acid insertions, the following nomenclature is used: original amino acid, position, original amino acid, inserted amino acid. Accordingly, the insertion of lysine after glycine at position 195 is represented as "Gly195GlyLys" or "G195GK." Insertions of multiple amino acids are represented as [original amino acid, position, original amino acid, inserted amino acid #1, inserted amino acid #2; etc.]. For example, the insertion of lysine and alanine after glycine at position 195 is represented as "Gly195GlyLysAla" or "G195GKA."

[0107] In such cases, the inserted amino acid residue(s) are numbered by adding lower case letters to the position number of the amino acid residue preceding the inserted amino acid residue(s). In the above example, the sequence would therefore be:

[0108] Parents: Variants: 195 195 195a 195b G GKA

[0109] Multiple changes Variants containing multiple alterations are separated by plus signs ("+"), for example, "Arg170Tyr+Gly195Glu" or "R170Y+G195E" represent substitutions of arginine and glycine at positions 170 and 195 by tyrosine and glutamic acid, respectively.

[0110] Different changesWhere different changes can be introduced at one position, the different changes are separated by commas, e.g., "Arg170Tyr,Glu" represents a substitution of arginine at position 170 with tyrosine or glutamic acid. Thus, "Tyr167Gly,Ala+Arg170Gly,Ala" represents the following variants:

[0111] “Tyr167Gly+Arg170Gly”, “Tyr167Gly+Arg170Ala”, “Tyr167Ala+Arg170Gly”, and “Tyr167Ala+Arg170Ala”. DETAILED DESCRIPTION

[0112] The present invention is directed to xylanase variants of a parent xylanase comprising a substitution at one or more positions corresponding to positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1, and wherein the variant has xylanase activity.

[0113] The present invention relates to xylanase variants of a parent xylanase, which further comprise a substitution at one or more positions corresponding to positions 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375 66, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530 and 540, and wherein the variants are identical to SEQ The polypeptide of claim 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of ID NO: 1, and wherein the variant has xylanase activity.

[0114] In one aspect, the invention relates to xylanase variants comprising a substitution at one or more positions corresponding to positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1; and wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1, and wherein the variant has xylanase activity, and wherein the xylanase variant has improved properties compared to the xylanase of SEQ ID NO: 1.

[0115] In one aspect, the invention relates to xylanase variants further comprising a substitution at one or more positions corresponding to positions 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358, 361, 362, 363, 364, 365, 366, 367, 368, 370, 371 of SEQ ID NO: 1. 66, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540; and wherein said variants are identical to SEQ The invention also provides a polypeptide having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of ID NO: 1, and wherein the variant has xylanase activity, and wherein the xylanase variant has improved properties relative to the parent.

[0116] The present invention relates to xylanase variants having one or more substitutions, which have improved properties, such as improved (increased) thermostability.

[0117] In one aspect, the invention relates to xylanase variants comprising a substitution at one or more positions corresponding to positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1; and wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1, and wherein the variant has xylanase activity, and wherein the xylanase variant has increased thermostability compared to the xylanase of SEQ ID NO: 1.

[0118] In one aspect, the invention relates to xylanase variants further comprising a substitution at one or more positions corresponding to positions 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358, 361, 362, 363, 364, 365, 366, 367, 368, 370, 371 of SEQ ID NO: 1. 66, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540; and wherein said variants are identical to SEQ The invention also provides a polypeptide having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1, and wherein the variant has xylanase activity, and wherein the xylanase variant has increased thermostability compared to the xylanase of SEQ ID NO: 1.

[0119] Xylanase variants

[0120] The invention provides xylanase variants of a parent xylanase comprising a substitution at one or more positions corresponding to positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has increased thermostability compared to the xylanase of SEQ ID NO: 1.

[0121] The present invention also provides xylanase variants of a parent xylanase, which further comprise a substitution at one or more positions corresponding to positions 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530 and 540, and wherein the variant has increased thermostability compared to the xylanase of SEQ ID NO: 1.

[0122] In one aspect, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the amino acid sequence of the parent alpha-amylase.

[0123] In one aspect, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to SEQ ID NO: 1.

[0124] In one aspect, the substituted amino acid residue is different from the naturally occurring amino acid residue at that position. In one embodiment, the substitution is selected from the group consisting of: A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y, provided that the substituted amino acid residue is different from the naturally occurring amino acid residue at that position.

[0125] 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 substitutions.

[0126] In another aspect, the variant comprises a substitution at two or more positions corresponding to any of positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has xylanase activity, and further wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1.

[0127] In another aspect, the variant comprises a substitution at three or more positions corresponding to any of positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has xylanase activity, and further wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1.

[0128] In another aspect, the variant comprises a substitution at four or more positions corresponding to any of positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has xylanase activity, and further wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1.

[0129] In another aspect, the variant comprises a substitution at five or more positions corresponding to any of positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has xylanase activity, and further wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1.

[0130] In another aspect, the variant comprises a substitution at six or more positions corresponding to any of positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has xylanase activity, and further wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1.

[0131] In another aspect, the variant comprises a substitution at each of the positions corresponding to any of positions 45, 149, 364, 258, 276, and 388 of SEQ ID NO: 1, and wherein the variant has xylanase activity, and further wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1.

[0132] In another aspect, the variant comprises a substitution at two or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0133] In another aspect, the variant comprises a substitution at three or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0134] In another aspect, the variant comprises substitutions at four or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0135] In another aspect, the variant comprises substitutions at five or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0136] In another aspect, the variant comprises substitutions at six or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0137] In another aspect, the variant comprises substitutions at seven or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0138] In another aspect, the variant comprises a substitution at eight or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0139] In another aspect, the variant comprises a substitution at nine or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0140] In another aspect, the variant comprises a substitution at ten or more positions corresponding to any of the following positions: 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358 of SEQ ID NO: 1. , 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant is the same as SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0141] In another aspect, the variant comprises a substitution at each of the positions corresponding to positions 45, 149, 364, 258, 276, 388, 9, 11, 18, 19, 20, 24, 25, 28, 40, 60, 61, 69, 70, 77, 79, 92, 93, 95, 113, 117, 127, 161, 163, 168, 170, 173, 180, 187, 190, 192, 211, 214, 215, 219, 234, 243, 250, 252, 260, 281, 282, 286, 314, 334, 340, 350, 355, 356, 358, 366, 375, 384, 385, 386, 389, 391, 393, 394, 395, 396, 446, 459, 468, 469, 470, 471, 472, 473, 474, 476, 477, 478, 480, 481, 483, 484, 495, 496, 497, 498, 499, 500, 501, 503, 522, 525, 526, 527, 528, 529, 530, and 540, and wherein the variant has xylanase activity, and further wherein the variant has xylanase activity, and further wherein the variant is identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0142] In one aspect, the variant comprises one or more of the following substitutions at positions corresponding to the following positions: NO:1 D9, D11, A18, S19, A20, A24, A25, M28, C40, V45, C60, Q61, C69, T70, Q 77, A79, S92, A93, D95, D113, A117, N127, L149, C161, N163, N168, A170, S17 3. T180, G187, S190, D192, T211, S214, T215, H219, V234, W250, A252, V258 , N260, A276, L281, S282, A286, Q314, H334, A340, V350, N355, L356, H358, A , S481, R483, L484, W495, Q496, V497, V498, A499, V500, S501, G503, C522, D525, G526, N527, S528, N529, L530, and C540, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0143] In one aspect, the variant comprises one or more of the following substitutions at positions corresponding to the following positions: NO:1's D9E, D11E, A18V, S19T, A20H, A20P, A24H, A24K, A25W, M28P, C40A, C40L, C40S, C40V, V45C, V45I, V45L, V45N, V45T, C60A, C60L, C60S, C60V, Q61K, Q61R, C69A, C69L, C69S, C69V, T70R, Q77E, A79C, S92D, S92N, A93S, A93T, D95N, D113T, A117C, A117S, N127D, L149R, C161L, C161S, C161V, N1 63H, N168G, A170S, S173Y, T180Q, G187K, G187L, G187S, S190E, D192E, T2 11H, S214E, S214Q, S214Y, T215I, T215K, T215V, H219I, H219V, V234P, C2 43L, C243S, C243V, W250Y, A252S, V258P, V258R, N260H, A276C, A276D, A2 76F, A276N, A276Q, A276S, A276T, L281V, S282N, A286E, A286S, Q314A, H3 34D, A340G, V350L, N355G, L356M, H358D, H358T, A364G, T366I, T366V, C 375A, C375L, C375S, C375V, Q384A, Q385C, Y386G, S388A, S388H, S388K, S 388L, S388R,, S389H, S389V, Y391V, V393H, V393R, G394A, G394D, G394Q, N395D, C396A, C396L, C396A, C396S, C396V, D446T, R459V, C468A, C468L, C468S, C468V, I469T, D470A, D470K, D470T, D470V, L471R, A472I, A472L, S473G, S473K, N474G, N476D, T477K, T477V, L478N, L478P, T480L, T480N, S481A, R483V, L484D, L484K, L484S, W495E, W495I, W495S, Q496E, Q496W, Q496R, V497D, V497E, V497P, V497W, V498I, A499L, A499Y, V500T, S501E,S501N, G503L, C522A, C522S, C522V, D525L, G526T, N527H, S528H, N529T, L530R, C540A, C540L, C540S, and C540V, and wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1.

[0144] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 9 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 9 is substituted with Ala, Arg, Asn, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution D9E of the polypeptide of SEQ ID NO: 1.

[0145] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 11 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 3 is substituted with Ala, Arg, Asn, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution D11E of the polypeptide of SEQ ID NO: 1.

[0146] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 18 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 18 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A18V of the polypeptide of SEQ ID NO: 1.

[0147] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 19 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 19 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution S19T of the polypeptide of SEQ ID NO: 1.

[0148] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 20 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 20 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution A20H or A20P of the polypeptide of SEQ ID NO: 1.

[0149] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 24 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 24 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A24H or A24K of the polypeptide of SEQ ID NO: 1.

[0150] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 25 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 25 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution A25W of the polypeptide of SEQ ID NO: 1.

[0151] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 28 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 28 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution M28P of the polypeptide of SEQ ID NO: 1.

[0152] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 40 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 40 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution C40A or C40L or C40S or C40V of the polypeptide of SEQ ID NO: 1.

[0153] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 45 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 45 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Tyr. In another aspect, the variant comprises or consists of the substitution V45C or V45I or V45L, V45N or V45T of the polypeptide of SEQ ID NO: 1.

[0154] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 60 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 60 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution C60A, C60L, C60S, or C60V of the polypeptide of SEQ ID NO: 1.

[0155] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 61 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 61 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution Q61K or Q61R of the polypeptide of SEQ ID NO: 1.

[0156] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 69 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 69 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution C69A or C69L or C69S or C69V of the polypeptide of SEQ ID NO: 1.

[0157] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 70 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 70 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution T70R of the polypeptide of SEQ ID NO: 1.

[0158] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 77 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 77 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution Q77E of the polypeptide of SEQ ID NO: 1.

[0159] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 79 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 79 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution A79C of the polypeptide of SEQ ID NO: 1.

[0160] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 92 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 92 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S92D or S92N of the polypeptide of SEQ ID NO: 1.

[0161] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 93 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 93 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A93S or A93T of the polypeptide of SEQ ID NO: 1.

[0162] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 95 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 95 is substituted with Ala, Arg, Asn, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution D95N of the polypeptide of SEQ ID NO: 1.

[0163] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 113 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 113 is substituted with Ala, Arg, Asn, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution D113T of the polypeptide of SEQ ID NO: 1.

[0164] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 117 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 117 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution A117C or A117S of the polypeptide of SEQ ID NO: 1.

[0165] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 127 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 127 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution N127D of the polypeptide of SEQ ID NO: 1.

[0166] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 149 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 149 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution L149R of the polypeptide of SEQ ID NO: 1.

[0167] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 161 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 161 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution C161L, C161S, or C161V of the polypeptide of SEQ ID NO: 1.

[0168] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 163 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 163 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution N163H of the polypeptide of SEQ ID NO: 1.

[0169] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 168 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 168 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution N168G of the polypeptide of SEQ ID NO: 1.

[0170] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 170 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 170 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A170S of the polypeptide of SEQ ID NO: 1.

[0171] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 173 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 173 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution S173Y of the polypeptide of SEQ ID NO: 1.

[0172] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 180 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 180 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution T180Q of the polypeptide of SEQ ID NO: 1.

[0173] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 187 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 187 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution G187K or G187L or G187S of the polypeptide of SEQ ID NO: 1.

[0174] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 190 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 190 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S190E of the polypeptide of SEQ ID NO: 1.

[0175] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 192 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 192 is substituted with Ala, Arg, Asn, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution D192E of the polypeptide of SEQ ID NO: 1.

[0176] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 211 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 211 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution T211H of the polypeptide of SEQ ID NO: 1.

[0177] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 214 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 214 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S214E, S214Q, or S214Y of the polypeptide of SEQ ID NO: 1.

[0178] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 215 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 215 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution T215I, T215K or T215V of the polypeptide of SEQ ID NO: 1.

[0179] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 219 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 219 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution H219I or H219V of the polypeptide of SEQ ID NO: 1.

[0180] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 234 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 234 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Tyr. In another aspect, the variant comprises or consists of the substitution V234P of the polypeptide of SEQ ID NO: 1.

[0181] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 243 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 243 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution C243L or C243S or C243V of the polypeptide of SEQ ID NO: 1.

[0182] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 250 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 250 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Tyr or Val. In another aspect, the variant comprises or consists of the substitution W250Y of the polypeptide of SEQ ID NO: 1.

[0183] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 252 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 252 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution A252S of the polypeptide of SEQ ID NO: 1.

[0184] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 258 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 258 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Tyr. In another aspect, the variant comprises or consists of the substitution V258P or V258R of the polypeptide of SEQ ID NO: 1.

[0185] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 260 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 260 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution N260H of the polypeptide of SEQ ID NO: 1.

[0186] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 276 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 276 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution A276C or A276D or A276F or A276N or A276Q or A276S or A276T of the polypeptide of SEQ ID NO: 1.

[0187] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 281 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 281 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution L281V of the polypeptide of SEQ ID NO: 1.

[0188] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 282 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 282 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S282N of the polypeptide of SEQ ID NO: 1.

[0189] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 286 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 286 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A286E or A286S of the polypeptide of SEQ ID NO: 1.

[0190] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 314 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 314 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution Q314A of the polypeptide of SEQ ID NO: 1.

[0191] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 334 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 334 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution H334D of the polypeptide of SEQ ID NO: 1.

[0192] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 340 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 340 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, Ile, Leu, Lys, Met, His, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A340G of the polypeptide of SEQ ID NO: 1.

[0193] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 350 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 3 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Tyr. In another aspect, the variant comprises or consists of the substitution V350L of the polypeptide of SEQ ID NO: 1.

[0194] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 355 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 355 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution N355G of the polypeptide of SEQ ID NO: 1.

[0195] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 356 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 356 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution L256M of the polypeptide of SEQ ID NO: 1.

[0196] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 358 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 358 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution H358D or H358T of the polypeptide of SEQ ID NO: 1.

[0197] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 364 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 364 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A364G of the polypeptide of SEQ ID NO: 1.

[0198] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 366 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 366 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution T366I or T366V of the polypeptide of SEQ ID NO: 1.

[0199] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 375 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 375 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution C375A or C375L or C375S or C375V of the polypeptide of SEQ ID NO: 1.

[0200] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 384 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 384 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution Q384A of the polypeptide of SEQ ID NO: 1.

[0201] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 385 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 385 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution Q385C of the polypeptide of SEQ ID NO: 1.

[0202] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 386 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 386 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Val. In another aspect, the variant comprises or consists of the substitution Y386G of the polypeptide of SEQ ID NO: 1.

[0203] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 388 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 388 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S388A, S388H, S388K, S388L, or S388R of the polypeptide of SEQ ID NO: 1.

[0204] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 389 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 389 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S389H or S389V of the polypeptide of SEQ ID NO: 1.

[0205] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 391 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 391 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Val. In another aspect, the variant comprises or consists of the substitution Y391V of the polypeptide of SEQ ID NO: 1.

[0206] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 393 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 393 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Tyr. In another aspect, the variant comprises or consists of the substitution V393H or V393R of the polypeptide of SEQ ID NO: 1.

[0207] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 394 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 394 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution G394A, G394D, or G394Q of the polypeptide of SEQ ID NO: 1.

[0208] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 395 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 395 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution N395D of the polypeptide of SEQ ID NO: 1.

[0209] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 396 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 396 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution C396A or C396L or C396S or C396V of the polypeptide of SEQ ID NO: 1.

[0210] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 446 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 446 is substituted with Ala, Arg, Asn, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution D446T of the polypeptide of SEQ ID NO: 1.

[0211] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 459 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 459 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution R459V of the polypeptide of SEQ ID NO: 1.

[0212] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 468 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 468 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution C468A or C468L or C468S or C468V of the polypeptide of SEQ ID NO: 1.

[0213] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 469 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 469 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution I469T of the polypeptide of SEQ ID NO: 1.

[0214] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 470 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 470 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution D470A or D470K or D470T or D470V of the polypeptide of SEQ ID NO: 1.

[0215] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 471 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 471 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution L471R of the polypeptide of SEQ ID NO: 1.

[0216] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 472 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 472 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A472I or A472L of the polypeptide of SEQ ID NO: 1.

[0217] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 473 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 473 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S473G or S473K of the polypeptide of SEQ ID NO: 1.

[0218] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 474 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 474 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution N474G of the polypeptide of SEQ ID NO: 1.

[0219] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 476 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 476 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution N476D of the polypeptide of SEQ ID NO: 1.

[0220] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 477 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 477 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution T477K or T477V of the polypeptide of SEQ ID NO: 1.

[0221] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 478 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 478 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution L478N or L478P of the polypeptide of SEQ ID NO: 1.

[0222] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 480 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 480 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution T480L or T480N of the polypeptide of SEQ ID NO: 1.

[0223] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 481 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 481 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S481A of the polypeptide of SEQ ID NO: 1.

[0224] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 483 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 483 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution R483V of the polypeptide of SEQ ID NO: 1.

[0225] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 484 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 484 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution L484D, L484K, or L484S of the polypeptide of SEQ ID NO: 1.

[0226] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 495 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 495 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Tyr or Val. In another aspect, the variant comprises or consists of the substitution W495E or W495I or W495S of the polypeptide of SEQ ID NO: 1.

[0227] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 496 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 496 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution Q496E, Q496W or Q496R of the polypeptide of SEQ ID NO: 1.

[0228] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 497 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 497 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Tyr. In another aspect, the variant comprises or consists of the substitution V497D or V497E or V497P or V497W of the polypeptide of SEQ ID NO: 1.

[0229] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 498 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 498 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Tyr. In another aspect, the variant comprises or consists of the substitution V498I of the polypeptide of SEQ ID NO: 1.

[0230] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 499 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 499 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution A499L or A499Y of the polypeptide of SEQ ID NO: 1.

[0231] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 500 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 500 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp or Tyr. In another aspect, the variant comprises or consists of the substitution V500T of the polypeptide of SEQ ID NO: 1.

[0232] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 501 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 501 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S501E or S501N of the polypeptide of SEQ ID NO: 1.

[0233] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 503 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 503 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution G503L of the polypeptide of SEQ ID NO: 1.

[0234] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 522 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 522 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution C522A, C522S, or C522V of the polypeptide of SEQ ID NO: 1.

[0235] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 525 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 525 is substituted with Ala, Arg, Asn, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution D525L of the polypeptide of SEQ ID NO: 1.

[0236] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 526 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 526 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution G526T of the polypeptide of SEQ ID NO: 1.

[0237] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 527 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 527 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution N527H of the polypeptide of SEQ ID NO: 1.

[0238] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 528 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 528 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution S528H of the polypeptide of SEQ ID NO: 1.

[0239] In another aspect, the variant comprises or consists of a substitution at a position corresponding to position 529 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 529 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another aspect, the variant comprises or consists of the substitution N529T of the polypeptide of SEQ ID NO: 1.

[0240] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 530 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 530 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution L530R of the polypeptide of SEQ ID NO: 1.

[0241] In another aspect, the variant comprises or consists of a substitution at the position corresponding to position 540 of SEQ ID NO: 1. In another aspect, the amino acid at the position corresponding to position 540 is substituted with Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val. In another aspect, the variant comprises or consists of the substitution C540A or C540L or C540S or C540V of the polypeptide of SEQ ID NO: 1.

[0242] In one aspect, the variant comprises at least one substitution at a position corresponding to a position selected from the group consisting of: Y386G, Q385C, A276S, A276C, A276Q, A276F, A79C, A276N, V45L, S19T, H358D, L149R, A25W, V45N, I469T, S388A, A276T, S388H, S92D, D525L, S214Q, A364G, S388L, S388R, S473G, S389V, A20H, W495E, Y386Y, V386Y, 93H, G187L, Q61K, G187S, A286E, A276Y, V258P, Q496E, G394A, V393R, T366V, S389S, S92N, N527H, Q384A, V497D, D470T, A18V, Q496Q, Q496R, S214E, P362P, S389H, V258R, A276D, L281V, V45I and A117C, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0243] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: V45L+L149R, V45N+L149R, L149R+A364G, V258P+A276Q, V258P+A276S, A25W+L149R, V45L ... V45N+L149R, L149R+A364G, V258P+A276Q, V258P+A276S, A25W+L149R, V258P+A276S, A25W+L149R, V258P+A276Q, V L+149R, V45L+A276S, A25W+A276S, V45L+A276Q, V45L+V258P, A25W+V258P, A25W+A276Q, L149R+W250Y , V45L+S388K, V45L+A364G, V45N+V258P, V258P+S388K, A25W+V45L, A276Q+S388K, W250Y+A276Q, A276S +S388K, A276Q+L281V, W250Y+A276S, A25W+S388K, A276S+L281V, G187S+A276Q, S92D+A276S, L149R+V2 58R, V45N+S388K, A25W+A364G, V258P+L281V, V258R+A276S, G187S+A276S, G187K+A276S, V45L+S92D, V 45L+L281V, V45N+W250Y, V258R+A276Q, V45L+V258R, W250Y+S388K, V45N+G187K, A25W+V258R, G187K+ S388K, A25W+S92D, L281V+S388K, V45N+V258R, L281V+A364G, S92D+A364G, A25W+G187S, A25W+G187K, W 250Y+V258P, S92D+V258P, G187K+W250Y, V45N+S92D, G187S+A364G, G187S+L281V, G187S+S388K, G187S+V258R, S92D+G187S, V45L+D11E, L149R+S388K, L149R+D11E, A364G+D11E and S388K+D11E, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0244] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: V45L+L149R+V258P, V45L+L149R+A364G, V45L+L149R+W250Y, V45L+L149R+G187S, V45L+L149R+S282N, and V45L+S92D+L149R of SEQ ID NO: 1, and wherein the variant is identical to SEQ ID NO: 2. The polypeptide of NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0245] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of V45L+L149R+A252S+H334D, V45L+L149R+S190E+D446T, V45L+L149R+V258P+A364G, V45L+L149R+A276Q+A364G, V45L+L149R+A276S+A364G, V45L+L149R+V258P+A276S, V45L+L149R+V258P+A364G, V45L+L149R+A276Q+A364G, V45L+L149R+A276S+A364G, V45L+L149R+V258P+A276S, V45L+L149R L281V+A364G, L149R+V258P+A276S+A364G, V45L+V258P+A276S+A364G, A25W+V45L+L149R+A364G, V45L+L149R+V258R+A364G, V45L+L149R+G187K+A364G, V45L+L149R+G187S+A364G and V45L+L149R+W250Y+A364G, and wherein the variants are identical to SEQ ID The polypeptide of NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0246] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of V45L+A93S+L149R+A252S+H334D, V45L+A93S+L149R+A252S+H334D, V45L+A93S+L149R+V234P+A252S, V45L+A93S+L149R+A252S+H334D, V45L+A93S L149R+A252S+H334D, V45L+A93S+L149R+A252S+H334D, V45L+A93S+L149R+A252S+H334D, V45L+A93S+L149R S190E+D446T+R459V, V45L+L149R+V258P+A276SA364G, V45L+L149R+V258P+A276Q+A364G, A25W+V45L+L149R+V2 58P+A276S, V45L+L149R+A276Q+L281V+A364G, V45L+L149R+A276Q+S282N+A364G, A25W+V45L+L149R+V258P+A276 Q. V45L+T70R+L149R+A276Q+A364G, V45L+L149R+V258P+L281V+A364G, A25W+V45L+L149RA276Q+A364G, V45L+L14 9R+A276Q+Q314A+A364G, V45L+L149R+G187K+V258P+A364G, V45L+L149R+A276Q+A286E+A364G, V45L+L149R+A276 Q+H358T+A364G, A25W+V45N+L149R+V258P+A276S, V45L+N127D+L149R+A276Q+A364G, V45L+L149R+W250Y+A276Q +A364G、V45L+L149R+W250Y+V258P+A364G、V45L+L149R+A276Q+A364G+S388K、A25W+V45L+L149R+V258P+A364G、V 45L+L149R+N168G+A276Q+A364G, V45L+A117S+L149R+A276Q+A364G, A24K+V45L+L149R+A276Q+A364G, V45L+L149 R+A276Q+A286S+A364G, V45L+L149R+A170S+A276Q+A364G, V45L+L149R+T180Q+A276Q+A364G, V45L+L149R+A276QV350L+A364G, V45L+L149R+V258P+S282N+A364G, A25W+V45L+L149R+A276S+A364G, V45L+ L149R+G187S+V258P+A364G, A25W+L149R+V258P+A276S+A364G, V45L+L149R+G187L+A276Q A364G, A25W+V45L+V258P+A276S+A364G, V45L+L149R+N260H+A276Q+A364G, V45L+L149R+W25 0Y+V258R+A364G, V45L+L149R+N163H+A276Q+A364G, V45L+S92D+L149R+A276Q+A364G, V45L+ L149R+S173Y+A276Q+A364G, V45L+S92D+L149R+V258P+A364G, V45L+D113T+L149R+A276Q+A3 64G, V45L+L149R+G187S+V258R+A364G, V45L+L149R+V258R+A364G+S388K, V45L+L149R+G187K V45L+L149R+V258R+A364G, V45L+L149R+V258R+S282N+A364G, V45L+L149R+V258R+L281V+A364G, V45L+S92N+L149R+V258P+A364G, V45L+L149R+V258P+A364G+S388K and V45L+S92N+L149R+V258R+A364G, and wherein the variants are identical to SEQ ID The polypeptide of NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0247] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: SEQ A25W+V45L+A79C+L149R+V258P+A276S, V45L+L149R+V258P+A276S+H358T+A364G, A25W+V45L+L149R+V258P+A276S+A364G, V45L+L14 with IDNO:1 9R+V258P+A276S+L281V+A364G, V45L+A93S+L149R+A252S+H334D+A34 0G、V45L+L149R+V258P+A276S+A364G+S388K、V45L+L149R+N168G+V258 P+A276S+A364G, V45L+L149R+S173Y+V258P+A276S+A364G, V45L+A93S +L149R+A252S+H334D+A340G、A25W+V45L+L149R+V258P+A276S+H358T、 A25W+V45L+L149R+V258P+A276Q+A364G, A25W+V45L+L149R+S214E+V25 8P+A276S, V45L+L149R+A170S+V258P+A276S+A364G, A25W+V45L+L149R +S214Q+V258P+A276S、A25W+V45L+L149R+V258P+A276S+S388K、V45L+ A93S+L149R+V234P+A252S+H334D, V45L+N127D+L149R+V258P+A276S+A 364G, V45L+L149R+W250Y+V258P+A276S+A364G, A25W+V45L+L149R+W2 50Y+A276Q+A364G, V45L+L149R+T180Q+V258P+A276S+A364G, V45L+L14 9R+V258P+A276S+Q314A+A364G, V45L+A117S+L149R+V258P+A276S+A3 64G, V45N+L149R+V258P+A276S+A364G+S388K, V45L+L149R+V258P+A27 6Q+L281V+A364G, A25W+V45L+L149R+V258P+A276S+Q314A, V45L+L149R +V258P+A276S+A286E+A364G、A25W+V45L+L149R+A276Q+L281V+A364G、A25W+V45L+L149R+V258P+A276S+A286E、A25W+V45L+L149R+V258P+A276S+L281V、A25W+V45L+D113T+L149R+V258P+A276S、A25W+V45L+L149R+T180Q+V258P+A276S、A25W+V45L+L149R+V258P+A276S+A286S、V45L+L149R+G187L+A276Q+L281V+A364G、V45L+L149R+A276Q+L281V+V350L+A364G、V45L+L149R+A276Q+L281V+A364G+S388K、A25W+V45L+S92D+L149R+V258P+A276S、A25W+V45L+L149R+G187L+V258P+A276S、A25W+V45L+L149R+W250Y+V258P+A276S、V45L+D113T+L149R+V258P+A276S+A364G、V45L+T70R+L149R+A276Q+L281V+A364G、V45L+S92D+L149R+A276Q+L281V+A364G、V45L+D113T+L149R+A276Q+L281V+A364G、V45L+L149R+A276Q+L281V+Q314A+A364G、A25W+V45L+Q61K+L149R+V258P+A276S、D9E+A25W+V45L+L149R+V258P+A276S、V45L+T70R+L149R+V258P+A276S+A364G、V45L+L149R+N163H+V258P+A276S+A364G、V45L+L149R+T180Q+A276Q+L281V+A364G、V45L+L149R+A276Q+L281V+A286S+A364G、A25W+V45L+L149R+A170S+V258P+A276S、A25W+V45L+T70R+L149R+V258P+A276S、V45L+L149R+N168G+A276Q+L281V+A364G、V45L+L149R+S173Y+A276Q+L281V+A364G、V45L+L149R+W250Y+A276Q+L281V+A364G、A25W+V45L+L149R+A276Q+A286E+A364G、A25W+V45L+L149R+A276Q+A364G+S388K、V45L+N127D+L149R+A276Q+L281V+A364G、V45L+L149R+A276Q+L281V+A286E+A364G、A25W+V45L+A117S+L149R+V258P+A276S、A24K+V45L+L149R+V258P+A276S+A364G、V45L+L149R+V258P+A276S+S282N+A364G、V45L+A117S+L149R+A276Q+L281V+A364G、V45L+L149R+N260H+A276Q+L281V+A364G、A25W+V45L+L149R+N168G+V258P+A276S、A25W+V45L+L149R+G187S+V258P+A276S、A25W+V45L+L149R+V258P+A276S+V350L、A25W+V45L+Q61R+L149R+V258P+A276S、V45N+L149R+V258P+A276S+L281V+A364G、A25W+V45L+L149R+V258P+A276S+S282N、A25W+V45L+L149R+S173Y+V258P+A276S、A25W+V45L+L149R+A276Q+A286S+A364G、A25W+V45L+L149R+T215V+V258P+A276S、A25W+V45L+L149R+T215I+V258P+A276S、A25W+V45L+L149R+T211H+V258P+A276S、V45L+L149R+V258P+A276S+V350L+A364G、A25W+V45L+D113T+L149R+A276Q+A364G、A25W+V45N+L149R+V258P+A276S+A364G、A25W+V45L+L149R+H219I+V258P+A276S、M28P+V45L+L149R+V258P+A276S+A364G、A25W+V45L+T70R+L149R+A276Q+A364G、A25W+V45L+L149R+A276Q+Q314A+A364G、A25W+V45L+L149R+S214Y+V258P+A276S、V45L+L149R+A276Q+L281V+H358T+A364G、A25W+V45L+L149R+H219V+V258P+A276S、D11E+A25W+V45L+L149R+V258P+A276S、A25W+V45L+A117S+L149R+A276Q+A364G, A25W+V45L+L149R+G187L+A276Q+A364G, V45N+L149R+V258P+A276S+H358 T+A364G, A25W+V45L+L149R+N163H+A276Q+A364G, A25W+V45L+L149R+S173Y+A276Q+A364G, A25W+V45L+L149R+A27 6Q+S282N+A364G, A25W+V45L+L149R+A276Q+H358T+A364G, A25W+V45L+L149R+T180Q+A276Q+A364G, A25W+V45L+N1 27D+L149R+A276Q+A364G, A25W+V45L+L149R+A170S+A276Q+A364G, A25W+V45L+N127D+L149R+V258P+A276S, A25W+V 45L+L149R+N168G+A276Q+A364G, A25W+V45L+L149R+N260H+A276Q+A364G, A25W+V45L+L149R+G187K+V258P+A276S , A25W+M28P+V45L+L149R+V258P+A276S, V45L+L149R+N163H+A276Q+L281V+A364G, V45L+L149R+G187L+V258P+A27 6S+A364G, A25W+V45L+L149R+A276Q+V350L+A364G, V45L+L149R+V258P+A276S+N355G+A364G, A25W+V45L+L149R+V258P+A276S+N355G, A25W+V45L+S92D+L149R+A276Q+A364G and A25W+V45L+L149R+A276Q+N355G+A364G, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0248] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: SEQ IDNO:1's V45L+A79C+L149R+V258P+A276S+A364G+S388K, V45N+A79C+L149R+V258P+A276S+A364G+S388K, V45L+L149R+S214Q+V258P+A276S+H 358D+A364G, A25W+V45L+A79C+L149R+V258P+A276S+A364G, V45L+A79C +L149R+V258P+A276S+L281V+A364G、A25W+V45L+L149R+S214E+V258P+ A276S+A364G, V45L+L149R+S214Q+V258P+A276Q+A364G+S388K, V45N+ L149R+S214Q+V258P+A276S+A364G+S388K, V45L+L149R+S214Q+V258P+ A276S+A364G+S388K, V45L+L149R+S214E+V258P+A276S+H358T+A364G, A25W+V45L+L149R+S214E+V258P+A276Q+A364G, V45L+L149R+S214Q+V2 58P+A276S+L281V+A364G, V45L+N127D+L149R+V258P+A276S+A364G+S 388K, V45L+L149R+V258P+A276S+H358T+A364G+S388K, V45L+L149R+G1 87L+V258P+A276S+A364G+S388K, V45L+L149R+W250Y+V258P+A276S+A3 64G+S388K, V45L+L149R+V258P+A276S+A286E+A364G+S388K, V45L+L14 9R+V258P+A276S+S282N+A364G+S388K, A25W+V45L+L149R+V258P+A276 S+A364G+S388K, V45L+L149R+S214Q+V258P+A276S+H358T+A364G, A25W +V45L+L149R+S214Q+V258P+A276S+A364G, V45L+L149R+N168G+V258P+ A276S+A364G+S388K, V45L+A117S+L149R+V258P+A276S+A364G+S388K,A25W+V45L+L149R+V258P+A276S+H358T+A364G、V45L+L149R+V258P+N260H+A276S+A364G+S388K、V45L+L149R+T215I+V258P+A276S+A364G+S388K、V45L+Q61K+L149R+V258P+A276S+H358T+A364G、V45L+L149R+V258P+A276S+Q314A+H358T+A364G、V45L+L149R+T180Q+V258P+A276S+A364G+S388K、V45L+L149R+V258P+A276S+Q314A+A364G+S388K、A25W+V45L+L149R+V258P+A276S+A286S+A364G、V45L+L149R+H219I+V258P+A276S+H358T+A364G、V45L+L149R+V258P+A276S+V350L+A364G+S388K、D11E+V45L+L149R+V258P+A276S+A364G+S388K、V45L+D113T+L149R+V258P+A276S+A364G+S388K、V45L+L149R+G187K+V258P+A276S+A364G+S388K、M28P+V45L+L149R+V258P+A276S+A364G+S388K、V45L+L149R+S173Y+V258P+A276S+A364G+S388K、A25W+V45L+L149R+V258P+A276S+Q314A+A364G、V45L+L149R+G187L+V258P+A276S+H358T+A364G、V45L+L149R+T215V+V258P+A276S+H358T+A364G、V45L+T70R+L149R+V258P+A276S+A364G+S388K、V45L+L149R+V258P+A276S+V350L+H358T+A364G、D9E+V45L+L149R+V258P+A276S+H358T+A364G、V45L+L149R+T211H+V258P+A276S+H358T+A364G、V45L+L149R+V258P+A276S+L281V+A364G+S388K、V45L+L149R+V258P+A276S+S282N+H358T+A364G、V45L+L149R+T215I+V258P+A276S+H358T+A364G、A25W+V45L+L149R+S173Y+V258P+A276S+A364G、V45L+Q61K+L149R+V258P+A276S+A364G+S388K、A25W+V45L+Q61K+L149R+V258P+A276S+A364G、V45L+L149R+S214E+V258P+A276S+L281V+A364G、V45L+L149R+V258P+A276S+A286E+H358T+A364G、D9E+V45L+L149R+V258P+A276S+A364G+S388K、V45L+S92D+L149R+V258P+A276S+A364G+S388K、A25W+V45L+L149R+V258P+A276S+A286E+A364G、V45L+L149R+N168G+V258P+A276S+L281V+A364G、V45L+Q61R+L149R+V258P+A276S+H358T+A364G、V45L+L149R+G187S+V258P+A276S+A364G+S388K、V45L+L149R+V258P+A276S+L281V+Q314A+A364G、V45L+L149R+V258P+A276S+L281V+H358T+A364G、V45L+L149R+A170S+V258P+A276S+H358T+A364G、V45L+L149R+A170S+V258P+A276S+A364G+S388K、V45L+L149R+T215V+V258P+A276S+A364G+S388K、V45L+L149R+V258P+A276Q+H358T+A364G+S388K、A25W+V45N+L149R+S214E+V258P+A276S+A364G、V45L+L149R+V258P+A276S+A286S+H358T+A364G、A25W+V45L+L149R+G187S+V258P+A276S+A364G、V45L+L149R+T180Q+V258P+A276S+L281V+A364G、V45L+S92D+L149R+V258P+A276S+L281V+A364G、V45L+Q61R+L149R+V258P+A276S+L281V+A364G、V45L+L149R+A170S+V258P+A276S+L281V+A364G、D11E+A25W+V45L+L149R+V258P+A276S+A364G、A25W+V45L+Q61R+L149R+V258P+A276S+A364G、A25W+V45L+L149R+T215V+V258P+A276S+A364G、D9E+V45L+L149R+V258P+A276S+L281V+A364G、A25W+V45L+L149R+V258P+A276S+V350L+A364G、V45L+L149R+H219V+V258P+A276S+L281V+A364G、V45L+L149R+T180Q+V258P+A276S+H358T+A364G、V45L+L149R+T215V+V258P+A276S+L281V+A364G、A25W+V45L+L149R+V258P+A276S+S282N+A364G、A25W+V45L+L149R+T215I+V258P+A276S+A364G、A25W+V45L+L149R+H219I+V258P+A276S+A364G、V45L+A117S+L149R+V258P+A276S+L281V+A364G、D9E+A25W+V45L+L149R+V258P+A276S+A364G、V45L+L149R+S214Y+V258P+A276S+A364G+S388K、A25W+V45L+L149R+T180Q+V258P+A276S+A364G、A25W+V45L+L149R+V258P+A276S+L281V+A364G、V45L+N127D+L149R+V258P+A276S+L281V+A364G、V45L+L149R+S173Y+V258P+A276S+H358T+A364G、V45L+Q61R+L149R+V258P+A276S+A364G+S388K、V45L+L149R+V258P+A276S+L281V+A286E+A364G、A25W+V45L+L149R+W250Y+V258P+A276S+A364G、A25W+V45L+L149R+V258P+N260H+A276S+A364G、V45L+L149R+V258P+A276S+L281V+V350L+A364G、A25W+V45L+L149R+A170S+V258P+A276S+A364G、V45L+L149R+V258P+A276S+L281V+A286S+A364G、V45L+L149R+V258P+A276S+L281V+S282N+A364G、D11E+V45L+L149R+V258P+A276S+L281V+A364G、V45L+Q61K+L149R+V258P+A276S+L281V+A364G、V45L+L149R+T215I+V258P+A276S+L281V+A364G、A25W+V45L+S92D+L149R+V258P+A276S+A364G、V45L+L149R+S214Y+V258P+A276S+L281V+A364G、V45L+L149R+T211H+V258P+A276S+L281V+A364G、A25W+V45L+L149R+G187L+V258P+A276S+A364G、V45L+S92D+L149R+V258P+A276S+H358T+A364G、V45L+L149R+G187K+V258P+A276S+H358T+A364G、V45L+L149R+N163H+V258P+A276S+L281V+A364G、A25W+V45L+T70R+L149R+V258P+A276S+A364G、V45L+L149R+S173Y+V258P+A276S+L281V+A364G、V45L+L149R+G187L+V258P+A276S+L281V+A364G、V45L+L149R+G187K+V258P+A276S+L281V+A364G、V45L+L149R+W250Y+V258P+A276S+H358T+A364G、V45L+L149R+T211H+V258P+A276S+A364G+S388K、V45L+L149R+N163H+V258P+A276S+A364G+S388K、V45L+L149R+V258P+A276S+A286S+A364G+S388K、A25W+V45L+L149R+S214Y+V258P+A276S+A364G、A25W+V45L+D113T+L149R+V258P+A276S+A364G、V45L+T70R+L149R+V258P+A276S+L281V+A364G、A25W+V45L+N127D+L149R+V258P+A276S+A364G、V45L+T70R+L149R+V258P+A276S+H358T+A364G、V45L+L149R+H219I+V258P+A276S+L281V+A364G、A25W+V45L+A117S+L149R+V258P+A276S+A364G、A25W+V45L+L149R+N168G+V258P+A276S+A364G、V45L+N127D+L149R+V258P+A276S+H358T+A364G、A25W+V45L+L149R+H219V+V258P+A276S+A364G、D11E+V45L+L149R+V258P+A276S+H358T+A364G、V45L+L149R+G187S+V258P+A276S+L281V+A364G、A25W+V45L+L149R+N163H+V258P+A276S+A364G、A25W+V45L+L149R+G187K+V258P+A276S+A364G、V45L+L149R+V258P+N260H+A276S+H358T+A364G、V45L+D113T+L149R+V258P+A276S+L281V+A364G、V45L+D113T+L149R+V258P+A276S+H358T+A364G、V45L+L149R+N168G+V258P+A276S+H358T+A364G、V45L+L149R+S214Y+V258P+A276S+H358T+A364G、V45L+A117S+L149R+V258P+A276S+H358T+A364G、A25W+M28P+V45L+L149R+V258P+A276S+A364G、M28P+V45L+L149R+V258P+A276S+L281V+A364G、M28P+V45L+L149R+V258P+A276S+H358T+A364G、V45L+L149R+N163H+V258P+A276S+H358T+A364G、V45L+L149R+T215K+V258P+A276S+H358T+A364G、V45L+L149R+H219I+V258P+A276S+A364G+S388K、V45L+L149R+T215K+V258P+A276S+A364G+S388K、V45L+L149R+W250Y+V258P+A276S+L281V+A364G, V45L+L149R+H219V+V258P+A276S+A364 G+S388K, A25W+V45L+L149R+V258P+A276S+N355G+A364G, V45L+L149R+V258P+A276S+N355 G+A364G+S388K, V45L+L149R+V258P+A276S+L281V+N355G+A364G, V45L+L149R+V258P+A276S+N355G+H358T+A364G and V45L+L149R+H219V+V258P+A276S+H358T+A364G, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0249] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: SEQ IDNO:1's V45L+A79C+L149R+S214E+V258P+A276S+A364G+S388K, V45L+A79C+L149R+S214Q+V258P+A276S+A364G+S388K, V45L+A79C+L149R+ V258P+A276S+Q314A+A364G+S388K, V45L+A79C+L149R+V258P+A276S+L281V+A364G+S388K, V45L+A79C+L149R+S173Y+V258P+A276S+A364G+ S388K, V45L+A79C+L149R+G187K+V258P+A276S+A364G+S388K, V45L+Q61R+A79C+L149R+V258P+A276S+A364G+S388K, V45L+A79C+L149R+N16 8G+V258P+A276S+A364G+S388K, V45L+A79C+L149R+T215V+V258P+A27 6S+A364G+S388K, V45L+A79C+L149R+V258P+A276S+A286S+A364G+S38 8K、V45L+A79C+L149R+H219V+V258P+A276S+A364G+S388K、V45L+A79C +L149R+A170S+V258P+A276S+A364G+S388K、D11E+V45L+A79C+L149R+ V258P+A276S+A364G+S388K, V45L+A79C+L149R+V258P+A276S+A286E+A364G+S388K, V45L+A79C+L149R+T180Q+V258P+A276S+A364G+S388K, V45L+A79C+L149R+H219I+V258P+A276S+A364G+S388K, V45L+L149R+S214E+V258P+A276S+H358D+A364G+D470T, V45L+A79C+L149R+V258P+A 276S+V350L+A364G+S388K, V45L+L149R+S214E+V258P+A276S+H358D+ A364G+D470T, V45L+A79C+D113T+L149R+V258P+A276S+A364G+S388K,<h2 style=";text-align:left;direction:ltr">V45L+A79C+N127D+L149R+V258P+A276S+A364G+S388K、D9E+V45L+A79C+L149R+V258P+A276S+A364G+S388K、V45L+L149R+S214E+V258P+A276S+H3 58D+A364G+D470T、V45L+A79C+L149R+W250Y+V258P+A276S+A364G+S388 K、V45L+L149R+S214E+V258P+A276S+H358D+A364G+D470T、V45L+L149R+S 214E+V258P+A276S+H358D+A364G+D470T、V45L+A79C+L149R+N163H+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D +A364G、A25W+V45L+A79C+L149R+S214E+V258P+A276S+A364G、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+D470T、V45L+A79C+S92D+L149R+V2 58P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H35 8D+A364G、V45L+L149R+S214Q+V258P+A276S+A286E+A364G+S388K、V45L+ L149R+S214Q+T215I+V258P+A276S+A364G+S388K、A25W+V45L+L149R+S21 4Q+V258P+A276S+A364G+S388K、V45L+L149R+A170S+S214Q+V258P+A276S +A364G+S388K、V45L+Q61K+L149R+S214Q+V258P+A276S+A364G+S388K、V 45L+L149R+N168G+S214Q+V258P+A276S+A364G+S388K、V45L+A79C+D95D+ L149R+V258P+A276S+A364G+S388K、V45L+Q77E+A79C+L149R+V258P+A276S+A364G+S388K、V45L+L149R+S214Q+V258P+A276S+S282N+A364G+S388K、V45L+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K、V45L+T70R+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K、V45L+L149R+G187K+S214Q+V258P+A276S+A364G+S388K、V45L+L149R+V258P+A276S+L281V+H358T+A364G+S388K、M28P+V45L+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+L149R+G187L+S214Q+V258P+A276S+A364G+S388K、V45L+L149R+S214Q+V258P+A276S+A286S+A364G+S388K、D9E+V45L+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K、V45L+A79C+L149R+V258P+A276S+H358T+A364G+S388K、A25W+V45L+L149R+S214E+V258P+A276S+H358T+A364G、A25W+V45L+L149R+S214E+V258P+A276S+A286E+A364G、A25W+V45L+Q61K+L149R+S214E+V258P+A276S+A364G、A25W+V45L+L149R+V258P+A276S+H358T+A364G+S388K、V45L+L149R+S214Q+V258P+A276S+V350L+A364G+S388K、D11E+V45L+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+L149R+H219I+V258P+A276S+H358T+A364G+S388K、V45L+S92D+L149R+S214Q+V258P+A276S+A364G+S388K、A25W+V45L+L149R+T211H+S214E+V258P+A276S+A364G、A25W+V45L+L149R+S214E+H219V+V258P+A276S+A364G、V45L+L149R+W250Y+V258P+A276S+H358T+A364G+S388K、D9E+V45L+L149R+V258P+A276S+H358T+A364G+S388K、V45L+L149R+H219V+V258P+A276S+H358T+A364G+S388K、V45L+A117S+L149R+S214E+V258P+A276S+A364G+S388K、D11E+A25W+V45L+L149R+S214E+V258P+A276S+A364G、V45L+L149R+V258P+A276S+Q314A+H358T+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388L、V45L+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K、V45L+D113T+L149R+S214Q+V258P+A276S+A364G+S388K、A25W+V45L+Q61R+L149R+S214E+V258P+A276S+A364G、A25W+V45L+L149R+S214E+V258P+A276S+L281V+A364G、D9E+A25W+V45L+L149R+S214E+V258P+A276S+A364G、V45L+Q61R+L149R+V258P+A276S+H358T+A364G+S388K、V45L+D113T+L149R+V258P+A276S+H358T+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R、V45L+Q61R+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276Q+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+L149R+T180Q+V258P+A276S+H358T+A364G+S388K、A25W+V45L+S92D+L149R+S214E+V258P+A276S+A364G、A25W+V45L+L149R+S214E+V258P+A276S+V350L+A364G、V45L+L149R+T211H+S214Q+V258P+A276S+A364G+S388K、A25W+V45L+L149R+S214E+H219I+V258P+A276S+A364G、V45L+L149R+T211H+V258P+A276S+H358T+A364G+S388K、A25W+V45L+A117S+L149R+S214E+V258P+A276S+A364G、A25W+V45L+L149R+S214E+T215V+V258P+A276S+A364G、V45L+A117S+L149R+V258P+A276S+H358T+A364G+S388K、V45L+L149R+N168G+V258P+A276S+H358T+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388H、A25W+V45L+L149R+S214E+T215I+V258P+A276S+A364G、V45L+N127D+L149R+V258P+A276S+H358T+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388A、V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、A25W+V45L+L149R+G187S+S214E+V258P+A276S+A364G、V45L+A117S+L149R+S214Y+V258P+A276S+A364G+S388K、A25W+V45L+L149R+S214E+V258P+A276S+A286S+A364G、V45L+L149R+V258P+A276S+A286S+H358T+A364G+S388K、V45L+L149R+S173Y+V258P+A276S+H358T+A364G+S388K、V45L+A79C+L149R+V258P+A276S+N355G+A364G+S388K、A25W+V45L+L149R+G187L+S214E+V258P+A276S+A364G、V45L+L149R+S214Q+V258P+A276S+L281V+A364G+S388K、V45L+L149R+S214Q+T215V+V258P+A276S+A364G+S388K、V45L+L149R+N163H+V258P+A276S+H358T+A364G+S388K, V45L+A79C+A117S+L149R+V258P+A276S+A364G+S388K, V4 5L+L149R+A170S+V258P+A276S+H358T+A364G+S388K, A25W+V45L+L149R+S214E+T215K+V258P+A276S+A364G, V45L+ S92D+L149R+V258P+A276S+H358T+A364G+S388K, V45L+L149R+S214Q+V258P+A276S+N355G+A364G+S388K, A25W+V45L+L149R+S214E+V258P+A276S+N355G+A364G and A25W+V45L+L149R+S214E+V258P+A276S+Q314A+A364G, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0250] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: SEQ IDNO:1's V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R+D470T, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T, V45L+A1 17S+L149R+S214Q+V258P+A276S+A364G+S388L+D470T, V45L+A117S+L14 9R+S214Q+V258P+A276Q+A364G+S388K+D470T, V45L+A117S+L149R+D192 E+S214Q+V258P+A276S+H358D+A364G, V45L+A117S+L149R+S214Q+V258P +A276S+A364G+S388A+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+ A364G+S388H+D470T, V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S 388K+D470T, V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S3 88K, V45L+A117S+L149R+D192E+S214Q+V258P+A276S+H358D+A364G, V45 L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K, V45L+A117S +L149R+S214Q+V258P+A276S+A364G+S388K+R483V, V45L+A117S+L149R+ S214E+V258P+A276S+A364G+S388K+D470T, V45L+A117S+L149R+S214Q+V 258P+A276S+H358D+A364G+S388R, V45L+A117S+L149R+S214Q+V258P+A2 76S+H358D+A364G+S388A, V45L+A117S+L149R+S214Q+V258P+A276S+A36 4G+Q384A+S388K, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364 G+S388L, V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K,V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394D、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S473G、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A、V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+L478P、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S481A、V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K、V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+L478N、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366V+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K、D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S501E、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S528H、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366I+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N474G、V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A499Y、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V500V、V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+T480N、V45L+A117S+L149R+G187S+S214Q+V258P+A276S+A364G+S388K、A25W+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N476N、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N476D、D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S481S、V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+T215I+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Q496R、V45L+A117S+L149R+A170S+S214Q+V258P+A276S+A364G+S388K、V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V497P、V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K、V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V、V45L+A117S+L149R+N168G+S214Q+V258P+A276S+A364G+S388K、V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、M28P+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+T477K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V、V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V500T、V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K, V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A 364G+S388K, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A472L, V45L+A117S+L149R+S214Q+V258P+A 276S+A364G+S388K+S473K, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A499L, V45L+A117S+L149R+S 214Q+V258P+A276S+A364G+S388K+V498I, V45L+A117S+L149R+N163H+S214Q+V258P+A276S+A364G+S388K, V45L+A 117S+L149R+S214Q+V258P+A276S+A364G+S388K+N527H,V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+ T477V, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G503L, V45L+A117S+L149R+G187L+S214Q+V258P+ A276S+A364G+S388K, V45L+A117S+L149R+S214Q+T215K+V258P+A276S+A364G+S388K, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q385C+S388K and V45L+A117S+L149R+S214Q+V258P+A276S+N355G+A364G+S388K, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0251] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: SEQ V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388R with IDNO:1 +D470T、V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K +D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+ D470T、V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S 388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388L+D 470T、V45L+A117S+L149R+S214E+V258P+A276S+A364G+S388K+D470T+R 483V, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R+D470T+R4 83V, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470A+R4 83V, V45L+A117S+L149R+S214Q+V258P+A276Q+A364G+S388K+D470T+R4 83V, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R4 83V, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D47 0T、V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R48 3V, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388H+D470T+R483 V. V45L+A79C+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T , V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T,V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388A+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q384A+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477K、V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476D、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478N、V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+G187L+S214Q+V258P+A276S+A364G+S388K+D470T、D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+S282N+A364G+S388K+D470T、D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476N、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394D+D470T、V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478P、V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K+D470T、V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+Q496R、V45L+A117S+N127D+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+A499Y、V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N529T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+L478N、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、M28P+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Y+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T477K、V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K、V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+T215I+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+Q496E、V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+W495I、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V498I、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V500V、D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+A170S+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q、V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+Q496Q、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+A499Y、V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q385C+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T480N、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V497P、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+A499L、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S501N、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388L+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V498I、V45L+A117S+L149R+S214Q+H219I+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+N163H+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K、V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D、V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K、V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N476D、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T477V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+L478P、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S481A、V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V500T、V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K、V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470V+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V500V、V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S481S、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V500T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+W495S、V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N474G、V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Q496Q、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S501E、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N476N、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S473K、V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Q496E、A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T480L、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K、V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Y391V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T480N、D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+A499L、V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V, V45L+A117S+L149R+S214Q+V258P+A276S+H35 8D+A364G+S388K+V393H, V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K, V45L+A117S+L149R+ S214Q+V258P+A276S+H358D+A364G+S388K+A472L, V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S3 88K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T480L、V45L+A117S+L149R+S214Q+V258P+A276S+ H358D+A364G+S388K+V393R, V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K, V45L+A117S+L14 9R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K, V45L+A117S+L149R+S214Q+V258P+A276S+N355G+A364G+S388K+ D470T, V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Y386G+S388K and V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S501E, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0252] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of V45L+A79C+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V, V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T, V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T, +A276S+H358D+A364G+S388K+D470T+R483V, V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T+L530R, V45L+A117S+L 149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T+R483V, V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T+L53 0R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G +S388K+D470A+R483V, V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V, V45L+A117S+L149R+S214Q+V258P+A2 76S+H358D+A364G+S388H+D470T+L530R, V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R, V45L+A117S+L149 R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T+L530R, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T+R483V,V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388L+D470T+R483V、V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N、V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366I+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S473G、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q384A+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N529T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T、V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T、V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S528H、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496R、V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T、D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S473K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388R+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K+D470T+R483V、V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+N260H+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+G187S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N474G、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501N、V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R+D470T、V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N、V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366V+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496Q、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366I+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L484S、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499L、V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V498I、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476D+R483V、D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501E、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A、V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481S、V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D+D470T+R483V、V45L+A117S+L149R+G187L+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V497P、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N527H、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+Q496Q、V45L+A117S+L149R+N168G+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476N+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477V+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478N+R483V、M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H+D470T+R483V、V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V497P、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V498I、V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477K+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+Q496E、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+Q496R、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+A499L、V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+S501E、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+N529T、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+S501N、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S481S+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478P+R483V、D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V、V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K+D470T+R483V、V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+N527H、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T、V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H+D470T+R483V、V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496E、V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+H219I+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+A499Y、V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V500T、V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G526T、V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+D525L、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476N、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H+D470T、V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T+L530R、A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K+D470T+R483V、V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+D95N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S473G、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G503L、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+D525L、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500T、V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480L、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V497E、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470V+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470K+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A472L、V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+T215K+V258P+A276S+A364G+S388K+D470T+R483V, V45L+A117S+L149R+S214Q+V258P+A276S+ A364G+S388K+D470T+R483V+V497W, V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+W495E, V45L+A 117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+D470T+R483V and V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T, and wherein the variants are consistent with SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0253] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R, V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V, V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R 483V, V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V, V45L+A117S+L149R+S214Q+V258P+A27 6S+L281V+H358D+A364G+S388K+D470T+R483V, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366I+S388K+D470T+R48 3V, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T+L530R, V45L+Q61K+A117S+L149R+S214Q+V258 P+A276S+H358D+A364G+S388K+D470T+L530R, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V , V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T+R483V, V45L+A117S+L149R+S214Q+V258P+A276S+ H358D+A364G+S388K+G394A+D470T+R483V, V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T+L530R,V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T+R483V+D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T+R483V、V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+W495E、V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Y391V+D470T+R483V、D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476N+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480L+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A+L530R、V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481S+R483V、V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496Q、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496E、V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P+R483V、A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484K、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N474G+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T+R483V、V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484S、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484D、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S528H、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S501N、V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+A499L、V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481S+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496E+L530R、V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V498I+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+A499Y、V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501N+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476N+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N+L530R、V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500V+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V500V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S501E、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+D525L+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G526T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N527H+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K+L530R、M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501E+L530R、V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499L+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A472I+L530R、V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+N527H、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497P、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V498I、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N+R483V、V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K+D470T+L530R、M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H+D470T+L530R、V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V500T、V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+D95N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T、V45L+A93T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499Y、V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+G503L、V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A+R483V、V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+G187S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+G526T、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+D525L、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S528H+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+I469T+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N529T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G503L+L530R、V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V497P+L530R、V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T+L530R、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497D、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N+R483V、V45L+T70R+D95N+A117S+L149R+S214Q+V258P+A276S+L356M+H358D+A364G+S388K、V45L+A117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T+R483V、V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497W、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R, V4 5L+A117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T+L530R, V45 L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V, V45L+ A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T+R483V, V45L+A1 17S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497E, V45L+A11 7S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R、V45L+A117 S+L149R+S214Q+V258P+A276S+H358D+A364G+Y386G+S388K+D470T+R483V and V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D+D470T+R483V, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0254] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, G+S388K+G394A+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, V45L+ T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A27 6S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394 A+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, V45L+T70R+A117S+L1 49R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358 D+A364G+S388K+G394A+D470T+R483V, V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+L530R,V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+ D470T+R483V+L530R, V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H 358D+A364G+S388K+D470T+R483V+L530R and V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V, and wherein the variants are identical to SEQ The polypeptide of ID NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0255] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R, V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R, V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R, +L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R, V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388 K+G394A+D470T+R483V+L530R, V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R48 3V, V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A286E+H358D+A364G+Q384A+S388K+N395D+D470T+R483V, V45L+A117S+L149R+G1 87K+S214E+T215I+V258P+A276S+A286E+H358D+A364G+S388K+V393H+D470T+R483V, V45L+A117S+L149R+G187K+S214E+T215I+V258P+A 276S+A286E+H358D+A364G+S388K+N395D+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+ G394A+C468V+D470T+R483V, V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468A+D470T+R483V,V45L+T70R+A117S+L149R+S214Q+C243V+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468L+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375V+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468S+D470T+R483V、V45L+C60L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+C69L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+C60A+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+C243L+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+C60S+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+C69A+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+C161S+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+C69V+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+C60V+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375A+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375S+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540A、V45L+C69S+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375L+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540L、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522S、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540S、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396S+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396A+D470T+R483V、C40L、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、C40A、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C40S、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、C40V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396V+D470T+R483V、V45L+T70R+A117S+L149R+C161V+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396L+D470T+R483V、V45L+T70R+A117S+L149R+C161L+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522A、V45L+T70R+A117S+L149R+S214Q+C243S+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V、V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522V and V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540V, and wherein the variants are identical to those in SEQ ID The polypeptide of NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0256] In one aspect, the variant contains substitutions at positions corresponding to positions selected from the group consisting of: V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394Q+D470T+R483V, V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V, V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V, V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V, V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V, V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V, V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V, V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V and V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V,and wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to the polypeptide of SEQ ID NO: 1.

[0257] In one aspect, the variant comprises a substitution at a position corresponding to a position selected from the group consisting of: V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V and V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V of SEQ ID NO: 1, and wherein the variant is identical to SEQ ID NO: 1. The polypeptide of NO: 1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity.

[0258] In one aspect, the xylanase variants of the invention have improved properties relative to a parent polypeptide, wherein the improved properties are selected from the group consisting of increased catalytic efficiency, increased catalytic rate, increased chemical stability, increased oxidative stability, increased pH activity, increased pH stability, increased specific activity, increased stability under storage conditions, increased substrate binding, increased substrate cleavage, increased substrate specificity, increased substrate stability, increased surface properties, increased thermal activity, and increased thermal stability.

[0259] In one aspect, the xylanase variants of the invention have improved properties relative to the parent polypeptide.

[0260] In one aspect, the xylanase variants of the invention have improved properties relative to the parent polypeptide, and wherein the improved property is increased thermostability.

[0261] In one aspect, the xylanase variant has improved (increased) thermostability relative to the parent xylanase.

[0262] In one aspect, the xylanase variant has improved (increased) thermostability relative to SEQ ID NO:1.

[0263] In one aspect, the xylanase variant has increased thermostability as measured by TSA as an increased melting temperature.

[0264] In one aspect, the xylanase variant has increased thermostability relative to SEQ ID NO: 1, which increased thermostability is measured using TSA as an increased melting temperature of at least 1°C, at least 1.5°C, at least 2°C, at least 2.5°C, at least 3°C, at least 3.5°C, at least 4.0°C, at least 4.5°C, or at least 5°C.

[0265] In one aspect, the xylanase variant has increased thermostability measured as an increased melting temperature using n-DSF.

[0266] In one aspect, the xylanase variant has increased thermostability relative to SEQ ID NO: 1, which increased thermostability is measured using n-DSF as an increased melting temperature of at least 1°C, at least 1.5°C, at least 2°C, at least 2.5°C, at least 3°C, at least 3.5°C, at least 4.0°C, at least 4.5°C, or at least 5°C.

[0267] In one aspect, the present invention is directed to xylanase variants comprising at least one of the following substitutions or combinations of substitutions:

[0268] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[0269] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394Q+D470T+R483V;

[0270] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V;

[0271] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[0272] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[0273] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V;

[0274] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[0275] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V;

[0276] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[0277] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[0278] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V;

[0279] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0280] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0281] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0282] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0283] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0284] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0285] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0286] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0287] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R;

[0288] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0289] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0290] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0291] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0292] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+L530R;

[0293] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R;

[0294] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R;

[0295] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+R483V+L530R;

[0296] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R;

[0297] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+R483V+L530R;

[0298] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[0299] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A286E+H358D+A364G+Q384A+S388K+N395D+D470T+R483V;

[0300] V45L+A117S+L149R+G187K+S214E+T215I+V258P+A276S+A286E+H358D+A364G+S388K+V393H+D470T+R483V;

[0301] V45L+A117S+L149R+G187K+S214E+T215I+V258P+A276S+A286E+H358D+A364G+S388K+N395D+D470T+R483V;

[0302] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T+R483V;

[0303] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0304] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0305] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+R483V;

[0306] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366I+S388K+D470T+R483V;

[0307] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0308] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T+L530R;

[0309] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0310] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0311] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T+R483V;

[0312] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T+R483V;

[0313] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T+L530R;

[0314] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T+R483V;

[0315] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0316] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468V+D470T+R483V;

[0317] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T

[0318] V45L+A79C+L149R+S214E+V258P+A276S+A364G+S388K;

[0319] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0320] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T+R483V;

[0321] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0322] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+L530R;

[0323] V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0324] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0325] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T+R483V;

[0326] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T+L530R;

[0327] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T+L530R;

[0328] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T+L530R;

[0329] V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T+R483V;

[0330] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T+R483V;

[0331] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D+R483V;

[0332] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T+R483V;

[0333] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K+R483V;

[0334] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496R;

[0335] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468A+D470T+R483V;

[0336] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+W495E;

[0337] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T+L530R;

[0338] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0339] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Y391V+D470T+R483V;

[0340] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0341] D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0342] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V+R483V;

[0343] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476N+R483V;

[0344] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R+D470T+R483V;

[0345] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480L+L530R;

[0346] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A+L530R;

[0347] V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0348] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481S+R483V;

[0349] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0350] V45L+T70R+A117S+L149R+S214Q+C243V+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0351] V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0352] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0353] V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0354] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D+L530R;

[0355] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T+R483V;

[0356] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496Q;

[0357] V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T+R483V;

[0358] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496E;

[0359] V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0360] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T+L530R;

[0361] V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T+L530R;

[0362] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P+R483V;

[0363] A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0364] V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0365] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484K

[0366] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N474G+L530R;

[0367] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T+L530R;

[0368] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T+R483V;

[0369] V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0370] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484S;

[0371] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0372] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484D;

[0373] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S528H;

[0374] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S501N;

[0375] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0376] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+A499L;

[0377] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0378] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T+R483V;

[0379] V45L+A79C+L149R+S214Q+V258P+A276S+A364G+S388K;

[0380] V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T+L530R;

[0381] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T+L530R;

[0382] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481S+L530R;

[0383] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496E+L530R;

[0384] V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0385] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V498I+L530R;

[0386] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A+R483V;

[0387] V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0388] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+A499Y;

[0389] V45L+A79C+L149R+V258P+A276S+Q314A+A364G+S388K;

[0390] V45L+A79C+L149R+V258P+A276S+L281V+A364G+S388K;

[0391] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T+L530R;

[0392] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501N+L530R;

[0393] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476N+L530R;

[0394] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V+L530R;

[0395] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+D470T+L530R;

[0396] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N+L530R;

[0397] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0398] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500V+L530R;

[0399] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V500V;

[0400] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P+L530R;

[0401] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S501E;

[0402] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+D525L+L530R;

[0403] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G526T+L530R;

[0404] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N527H+L530R;

[0405] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K+L530R;

[0406] M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0407] D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0408] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501E+L530R;

[0409] V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0410] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499L+L530R;

[0411] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A472I+L530R;

[0412] V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0413] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500T+L530R;

[0414] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+N527H;

[0415] V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0416] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N+L530R;

[0417] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497P;

[0418] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V498I;

[0419] V45L+A79C+L149R+S173Y+V258P+A276S+A364G+S388K;

[0420] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N+R483V;

[0421] V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0422] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T+L530R;

[0423] M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0424] V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0425] V45L+A79C+L149R+G187K+V258P+A276S+A364G+S388K;

[0426] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H+D470T+L530R;

[0427] V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0428] V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0429] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T+R483V;

[0430] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388L+D470T+R483V;

[0431] V45L+Q61R+A79C+L149R+V258P+A276S+A364G+S388K;

[0432] V45L+A79C+L149R+N168G+V258P+A276S+A364G+S388K;

[0433] V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0434] V45L+A79C+L149R+T215V+V258P+A276S+A364G+S388K;

[0435] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V500T;

[0436] V45L+A79C+L149R+V258P+A276S+A286S+A364G+S388K;

[0437] V45L+A79C+L149R+H219V+V258P+A276S+A364G+S388K;

[0438] V45L+A79C+L149R+A170S+V258P+A276S+A364G+S388K;

[0439] V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0440] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0441] V45L+D95N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T;

[0442] V45L+A79C+L149R+V258P+A276S+A364G+S388K;

[0443] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A+D470T+R483V;

[0444] V45L+A93T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499Y;

[0445] V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0446] V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0447] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N;

[0448] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T;

[0449] V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T;

[0450] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468L+D470T+R483V;

[0451] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T+L530R;

[0452] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366I+S388K+D470T;

[0453] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S473G;

[0454] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P;

[0455] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D+D470T;

[0456] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q384A+S388K+D470T+R483V;

[0457] D11E+V45L+A79C+L149R+V258P+A276S+A364G+S388K;

[0458] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L530R;

[0459] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N529T;

[0460] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T;

[0461] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0462] V45L+A79C+L149R+V258P+A276S+A286E+A364G+S388K;

[0463] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+G503L;

[0464] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T;

[0465] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T;

[0466] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0467] V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T;

[0468] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T;

[0469] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T;

[0470] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388R+D470T;

[0471] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S528H;

[0472] V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0473] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496R;

[0474] V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0475] V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T;

[0476] V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T;

[0477] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0478] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T;

[0479] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S473K;

[0480] V45L+A79C+L149R+T180Q+V258P+A276S+A364G+S388K;

[0481] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A+R483V;

[0482] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388R+D470T+R483V;

[0483] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K+D470T+R483V;

[0484] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0485] V45L+A117S+L149R+S214Q+V258P+N260H+A276S+H358D+A364G+S388K+D470T;

[0486] V45L+A117S+L149R+G187S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0487] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K;

[0488] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N474G;

[0489] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T;

[0490] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501N;

[0491] V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0492] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R+D470T;

[0493] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0494] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+D470T;

[0495] V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0496] V45L+A117S+L149R+G187S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0497] V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0498] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N;

[0499] V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0500] V45L+A79C+L149R+H219I+V258P+A276S+A364G+S388K;

[0501] V45L+L149R+S214E+V258P+A276S+H358D+A364G+D470T;

[0502] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0503] V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0504] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366V+S388K+D470T+R483V;

[0505] V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T+R483V;

[0506] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R+D470T+R483V;

[0507] V45N+A79C+L149R+V258P+A276S+A364G+S388K;

[0508] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496Q;

[0509] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q+D470T+R483V;

[0510] V45L+A79C+L149R+V258P+A276S+V350L+A364G+S388K;

[0511] V45L+L149R+S214E+V258P+A276S+H358D+A364G+D470T;

[0512] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366I+S388K+D470T+R483V;

[0513] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+G526T;

[0514] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L484S;

[0515] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0516] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499L;

[0517] V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T+L530R;

[0518] V45L+A79C+D113T+L149R+V258P+A276S+A364G+S388K;

[0519] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+D525L;

[0520] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V498I;

[0521] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388L+D470T;

[0522] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0523] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S528H+L530R;

[0524] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476D+R483V;

[0525] D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0526] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501E;

[0527] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A;

[0528] V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K+D470T;

[0529] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481S;

[0530] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0531] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D+D470T+R483V;

[0532] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+I469T+D470T+R483V;

[0533] V45L+A79C+N127D+L149R+V258P+A276S+A364G+S388K;

[0534] D9E+V45L+A79C+L149R+V258P+A276S+A364G+S388K;

[0535] V45L+L149R+S214E+V258P+A276S+H358D+A364G+D470T;

[0536] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0537] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N529T+L530R;

[0538] V45L+A79C+L149R+W250Y+V258P+A276S+A364G+S388K;

[0539] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V497P;

[0540] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N527H;

[0541] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+Q496Q;

[0542] V45L+A117S+L149R+N168G+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0543] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476N+R483V;

[0544] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477V+R483V;

[0545] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K+D470T+R483V;

[0546] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478N+R483V;

[0547] V45L+A117S+L149R+S214E+V258P+A276S+A364G+S388K+D470T+R483V;

[0548] M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0549] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H+D470T+R483V;

[0550] V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0551] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V497P;

[0552] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V498I;

[0553] V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T+L530R;

[0554] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375V+S388K+G394A+D470T+R483V;

[0555] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K+D470T+R483V;

[0556] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R+D470T+R483V;

[0557] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470A+R483V;

[0558] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477K+R483V;

[0559] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+Q496E;

[0560] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+Q496R;

[0561] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+A499L;

[0562] V45L+L149R+S214E+V258P+A276S+H358D+A364G+D470T;

[0563] V45L+L149R+S214E+V258P+A276S+H358D+A364G+D470T;

[0564] V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T;

[0565] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468S+D470T+R483V;

[0566] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V+D470T+R483V;

[0567] V45L+A117S+L149R+S214Q+V258P+A276Q+A364G+S388K+D470T+R483V;

[0568] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G503L+L530R;

[0569] V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0570] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D;

[0571] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T;

[0572] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0573] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K+D470T+R483V;

[0574] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+S501E;

[0575] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+N529T;

[0576] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+S501N;

[0577] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0578] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S481S+R483V;

[0579] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478P+R483V;

[0580] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0581] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V;

[0582] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V497P+L530R;

[0583] V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0584] V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0585] V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K+D470T+R483V;

[0586] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0587] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+N527H;

[0588] V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0589] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T;

[0590] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0591] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388H+D470T+R483V;

[0592] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H+D470T+R483V;

[0593] V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K+D470T+R483V;

[0594] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0595] V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0596] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496E;

[0597] V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0598] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T+R483V;

[0599] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T+L530R;

[0600] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T;

[0601] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T;

[0602] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0603] V45L+A117S+L149R+S214Q+H219I+V258P+A276S+A364G+S388K+D470T+R483V;

[0604] V45L+A79C+L149R+N163H+V258P+A276S+A364G+S388K;

[0605] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+A499Y;

[0606] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K+D470T+R483V;

[0607] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V500T;

[0608] V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0609] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500V;

[0610] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G526T;

[0611] V45L+C60L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0612] V45L+C69L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0613] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388A+D470T+R483V;

[0614] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T;

[0615] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497D;

[0616] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A+L530R;

[0617] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+D525L;

[0618] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476N;

[0619] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K+D470T;

[0620] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q384A+S388K+D470T;

[0621] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K+D470T;

[0622] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477K;

[0623] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H+D470T;

[0624] V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0625] V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T;

[0626] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A+D470T;

[0627] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476D;

[0628] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N+R483V;

[0629] V45L+C60A+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0630] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H+D470T;

[0631] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D+D470T;

[0632] A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0633] V45L+T70R+A117S+L149R+S214Q+C243L+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0634] V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T;

[0635] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478N;

[0636] V45L+C60S+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0637] V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K+D470T;

[0638] V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K+D470T+R483V;

[0639] V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[0640] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+A364G+S388K+D470T;

[0641] D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0642] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G;

[0643] V45L+C69A+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0644] V45L+T70R+A117S+L149R+C161S+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0645] V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T;

[0646] V45L+A117S+L149R+S214Q+V258P+A276S+S282N+A364G+S388K+D470T;

[0647] V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0648] V45L+D95N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S473G;

[0649] V45L+T70R+D95N+A117S+L149R+S214Q+V258P+A276S+L356M+H358D+A364G+S388K;

[0650] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0651] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476N;

[0652] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394D+D470T;

[0653] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0654] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G503L;

[0655] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K+D470T;

[0656] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A;

[0657] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q+D470T;

[0658] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R+D470T;

[0659] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478P;

[0660] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K+D470T;

[0661] V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0662] V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K+D470T;

[0663] V45L+C69V+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0664] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+D525L;

[0665] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0666] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500T;

[0667] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H+D470T;

[0668] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R+D470T;

[0669] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+Q496R;

[0670] V45L+A117S+N127D+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0671] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+A499Y;

[0672] V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T;

[0673] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480L;

[0674] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388L+D470T;

[0675] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K+D470T;

[0676] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0677] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V+D470T+R483V;

[0678] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N529T;

[0679] V45L+C60V+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0680] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V497E;

[0681] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+L478N;

[0682] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0683] M28P+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0684] V45L+A117S+L149R+S214Q+V258P+A276Q+A364G+S388K+D470T;

[0685] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470V+R483V;

[0686] V45L+A117S+L149R+S214Y+V258P+A276S+A364G+S388K+D470T+R483V;

[0687] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D;

[0688] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T477K;

[0689] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K;

[0690] V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0691] V45L+A117S+L149R+S214Q+T215I+V258P+A276S+A364G+S388K+D470T;

[0692] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+Q496E;

[0693] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K+D470T;

[0694] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+W495I;

[0695] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V498I;

[0696] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470K+R483V;

[0697] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V500V;

[0698] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0699] V45L+A117S+L149R+A170S+S214Q+V258P+A276S+A364G+S388K+D470T;

[0700] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V+D470T;

[0701] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K+D470T;

[0702] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477V;

[0703] A25W+V45L+A79C+L149R+S214E+V258P+A276S+A364G;

[0704] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q;

[0705] V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K+D470T;

[0706] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+Q496Q;

[0707] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375A+S388K+G394A+D470T+R483V;

[0708] V45L+A117S+L149R+D192E+S214Q+V258P+A276S+H358D+A364G;

[0709] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A472L;

[0710] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+A499Y;

[0711] V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K+D470T;

[0712] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q385C+S388K+D470T;

[0713] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388A+D470T;

[0714] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388H+D470T;

[0715] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T480N;

[0716] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V497P;

[0717] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+A499L;

[0718] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S501N;

[0719] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+D470T;

[0720] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K;

[0721] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375S+S388K+G394A+D470T+R483V;

[0722] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388L+D470T+R483V;

[0723] V45L+A79C+S92D+L149R+V258P+A276S+A364G+S388K;

[0724] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540A;

[0725] V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T;

[0726] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A;

[0727] V45L+C69S+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0728] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V498I;

[0729] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G;

[0730] V45L+A117S+L149R+S214Q+H219I+V258P+A276S+A364G+S388K+D470T;

[0731] V45L+A117S+L149R+N163H+S214Q+V258P+A276S+A364G+S388K+D470T;

[0732] V45L+L149R+S214Q+V258P+A276S+H358D+A364G;

[0733] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K;

[0734] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K;

[0735] V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K;

[0736] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D;

[0737] A25W+V45L+A79C+L149R+V258P+A276S+A364G;

[0738] V45L+L149R+S214Q+V258P+A276S+A286E+A364G+S388K;

[0739] V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0740] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K;

[0741] V45L+A117S+L149R+D192E+S214Q+V258P+A276S+H358D+A364G;

[0742] V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K;

[0743] V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K;

[0744] V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K;

[0745] V45L+L149R+S214Q+T215I+V258P+A276S+A364G+S388K;

[0746] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N476D;

[0747] V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[0748] V45L+A117S+L149R+S214Q+T215K+V258P+A276S+A364G+S388K+D470T+R483V;

[0749] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0750] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T477V;

[0751] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+L478P;

[0752] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S481A;

[0753] A25W+V45L+L149R+S214Q+V258P+A276S+A364G+S388K;

[0754] V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K+D470T;

[0755] V45L+A117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0756] V45L+A79C+L149R+V258P+A276S+L281V+A364G;

[0757] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+R483V;

[0758] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V500T;

[0759] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K;

[0760] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K;

[0761] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375L+S388K+G394A+D470T+R483V;

[0762] V45L+L149R+A170S+S214Q+V258P+A276S+A364G+S388K;

[0763] V45L+A117S+L149R+S214E+V258P+A276S+A364G+S388K+D470T;

[0764] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470V+R483V;

[0765] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V500V;

[0766] V45L+Q61K+L149R+S214Q+V258P+A276S+A364G+S388K;

[0767] V45L+L149R+N168G+S214Q+V258P+A276S+A364G+S388K;

[0768] V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K;

[0769] V45L+A79C+D95D+L149R+V258P+A276S+A364G+S388K;

[0770] V45L+Q77E+A79C+L149R+V258P+A276S+A364G+S388K;

[0771] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V497W;

[0772] V45L+L149R+S214Q+V258P+A276S+S282N+A364G+S388K;

[0773] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388R;

[0774] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S481S;

[0775] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V500T;

[0776] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540L;

[0777] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522S;

[0778] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+W495S;

[0779] V45L+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K;

[0780] V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0781] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497W;

[0782] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540S;

[0783] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396S+D470T+R483V;

[0784] V45L+T70R+L149R+S214Q+V258P+A276S+A364G+S388K;

[0785] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N474G;

[0786] V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K;

[0787] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Q496Q;

[0788] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V+D470T;

[0789] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396A+D470T+R483V;

[0790] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S501E;

[0791] A25W+V45L+L149R+S214E+V258P+A276S+A364G;

[0792] V45L+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K;

[0793] V45L+L149R+G187K+S214Q+V258P+A276S+A364G+S388K;

[0794] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N476N;

[0795] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S473K;

[0796] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K;

[0797] C40L+V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0798] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Q496E;

[0799] A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0800] V45L+L149R+V258P+A276S+L281V+H358T+A364G+S388K;

[0801] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A;

[0802] V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K;

[0803] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H;

[0804] M28P+V45L+L149R+S214Q+V258P+A276S+A364G+S388K;

[0805] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T480L;

[0806] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q384A+S388K;

[0807] V45L+A93S+L149R+A252S+H334D;

[0808] C40A+V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0809] V45L+L149R+G187L+S214Q+V258P+A276S+A364G+S388K;

[0810] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K;

[0811] V45L+L149R+S214Q+V258P+A276S+A286S+A364G+S388K;

[0812] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0813] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388L;

[0814] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K;

[0815] D9E+V45L+L149R+S214Q+V258P+A276S+A364G+S388K;

[0816] V45L+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K;

[0817] V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K;

[0818] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Y391V;

[0819] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K;

[0820] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394D;

[0821] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S473G;

[0822] V45L+A79C+L149R+V258P+A276S+H358T+A364G+S388K;

[0823] V45L+L149R+S214Q+V258P+A276Q+A364G+S388K;

[0824] A25W+V45L+L149R+S214E+V258P+A276S+H358T+A364G;

[0825] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T480N;

[0826] D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0827] V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K;

[0828] C40S+V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0829] C40V+V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0830] A25W+V45L+L149R+S214E+V258P+A276S+A286E+A364G;

[0831] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A;

[0832] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+A499L;

[0833] A25W+V45L+Q61K+L149R+S214E+V258P+A276S+A364G;

[0834] V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K;

[0835] A25W+V45L+L149R+V258P+A276S+H358T+A364G+S388K;

[0836] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+W495E;

[0837] A25W+V45L+A79C+L149R+V258P+A276S;

[0838] V45L+L149R+S214Q+V258P+A276S+V350L+A364G+S388K;

[0839] D11E+V45L+L149R+S214Q+V258P+A276S+A364G+S388K;

[0840] V45L+L149R+H219I+V258P+A276S+H358T+A364G+S388K;

[0841] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396V+D470T+R483V;

[0842] V45N+L149R+S214Q+V258P+A276S+A364G+S388K;

[0843] V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K;

[0844] V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0845] V45L+S92D+L149R+S214Q+V258P+A276S+A364G+S388K;

[0846] V45L+L149R+V258P+A276S+H358T+A364G;

[0847] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+L478P;

[0848] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S481A;

[0849] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K;

[0850] A25W+V45L+L149R+T211H+S214E+V258P+A276S+A364G;

[0851] A25W+V45L+L149R+S214E+H219V+V258P+A276S+A364G;

[0852] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V;

[0853] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H;

[0854] V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K;

[0855] V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K;

[0856] V45L+L149R+W250Y+V258P+A276S+H358T+A364G+S388K;

[0857] D9E+V45L+L149R+V258P+A276S+H358T+A364G+S388K;

[0858] V45L+L149R+H219V+V258P+A276S+H358T+A364G+S388K;

[0859] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+A472L;

[0860] A25W+V45L+L149R+V258P+A276S+A364G;

[0861] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K;

[0862] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+L478N;

[0863] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R;

[0864] V45L+A117S+L149R+S214E+V258P+A276S+A364G+S388K;

[0865] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366V+S388K;

[0866] V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K;

[0867] D11E+A25W+V45L+L149R+S214E+V258P+A276S+A364G;

[0868] V45L+T70R+A117S+L149R+C161V+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0869] V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K;

[0870] V45L+L149R+V258P+A276S+Q314A+H358T+A364G+S388K;

[0871] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[0872] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q;

[0873] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D;

[0874] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H;

[0875] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S501E;

[0876] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S528H;

[0877] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0878] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388L;

[0879] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396L+D470T+R483V;

[0880] V45L+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K;

[0881] V45L+D113T+L149R+S214Q+V258P+A276S+A364G+S388K;

[0882] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T480L;

[0883] V45L+A93S+L149R+A252S+H334D;

[0884] V45L+A93S+L149R+V234P+A252S;

[0885] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H;

[0886] A25W+V45L+Q61R+L149R+S214E+V258P+A276S+A364G;

[0887] V45L+A117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T;

[0888] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H;

[0889] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366I+S388K;

[0890] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N474G;

[0891] A25W+V45L+L149R+S214E+V258P+A276S+L281V+A364G;

[0892] D9E+A25W+V45L+L149R+S214E+V258P+A276S+A364G;

[0893] V45L+A117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[0894] V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K;

[0895] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R;

[0896] V45L+Q61R+L149R+V258P+A276S+H358T+A364G+S388K;

[0897] V45L+L149R+S214Q+V258P+A276S+A364G+S388K;

[0898] V45L+D113T+L149R+V258P+A276S+H358T+A364G+S388K;

[0899] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K;

[0900] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R;

[0901] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A499Y;

[0902] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V500V;

[0903] V45L+Q61R+L149R+S214Q+V258P+A276S+A364G+S388K;

[0904] V45L+L149R+S214E+V258P+A276S+H358T+A364G;

[0905] V45L+A117S+L149R+S214Q+V258P+A276Q+A364G+S388K;

[0906] V45L+L149R+V258P+A276S+L281V+A364G;

[0907] V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K;

[0908] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+T480N;

[0909] V45L+A117S+L149R+G187S+S214Q+V258P+A276S+A364G+S388K;

[0910] A25W+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[0911] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[0912] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N476N;

[0913] A25W+V45L+L149R+S214E+V258P+A276Q+A364G;

[0914] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N476D;

[0915] V45L+L149R+S214Q+V258P+A276S+L281V+A364G;

[0916] V45L+A93S+L149R+A252S+H334D+A340G;

[0917] V45L+A93S+L149R+A252S+H334D;

[0918] V45L+A93S+L149R+A252S+H334D;

[0919] V45L+L149R+A252S+H334D;

[0920] V45L+N127D+L149R+V258P+A276S+A364G+S388K;

[0921] V45L+L149R+V258P+A276S+H358T+A364G+S388K;

[0922] V45L+L149R+V258P+A276S+A364G+S388K;

[0923] D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[0924] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S481S;

[0925] V45L+L149R+N168G+V258P+A276S+A364G;

[0926] V45L+L149R+T180Q+V258P+A276S+H358T+A364G+S388K;

[0927] V45L+L149R+G187L+V258P+A276S+A364G+S388K;

[0928] V45L+L149R+W250Y+V258P+A276S+A364G+S388K;

[0929] V45L+L149R+V258P+A276S+A286E+A364G+S388K;

[0930] V45L+L149R+V258P+A276S+S282N+A364G+S388K;

[0931] A25W+V45L+L149R+V258P+A276S+A364G+S388K;

[0932] V45L+L149R+S214Q+V258P+A276S+H358T+A364G;

[0933] V45L+L149R+S173Y+V258P+A276S+A364G;

[0934] V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K;

[0935] V45L+A93S+L149R+A252S+H334D;

[0936] V45L+A93S+L149R+A252S+H334D+A340G;

[0937] V45L+L149R+S190E+D446T+R459V;

[0938] A25W+V45L+L149R+V258P+A276S+H358T;

[0939] A25W+V45L+S92D+L149R+S214E+V258P+A276S+A364G;

[0940] A25W+V45L+L149R+S214E+V258P+A276S+V350L+A364G;

[0941] A25W+V45L+L149R+S214Q+V258P+A276S+A364G;

[0942] V45L+L149R+N168G+V258P+A276S+A364G+S388K;

[0943] V45L+A117S+L149R+V258P+A276S+A364G+S388K;

[0944] A25W+V45L+L149R+V258P+A276S+H358T+A364G;

[0945] V45L+L149R+V258P+N260H+A276S+A364G+S388K;

[0946] V45L+L149R+T215I+V258P+A276S+A364G+S388K;

[0947] A25W+V45L+L149R+V258P+A276Q+A364G;

[0948] V45L+T70R+A117S+L149R+C161L+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[0949] A25W+V45L+L149R+S214E+V258P+A276S;

[0950] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K;

[0951] V45L+L149R+T211H+S214Q+V258P+A276S+A364G+S388K;

[0952] V45L+Q61K+L149R+V258P+A276S+H358T+A364G;

[0953] V45L+L149R+V258P+A276S+Q314A+H358T+A364G;

[0954] V45L+L149R+T180Q+V258P+A276S+A364G+S388K;

[0955] V45L+L149R+V258P+A276S+Q314A+A364G+S388K;

[0956] A25W+V45L+L149R+V258P+A276S+A286S+A364G;

[0957] V45L+L149R+S190E+D446T;

[0958] V45L+L149R+V258P+A276S+A364G;

[0959] V45L+L149R+A170S+V258P+A276S+A364G;

[0960] V45L+L149R+V258P+A276Q+A364G;

[0961] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522A;

[0962] V45L+L149R+H219I+V258P+A276S+H358T+A364G;

[0963] V45L+L149R+V258P+A276S+V350L+A364G+S388K;

[0964] D11E+V45L+L149R+V258P+A276S+A364G+S388K;

[0965] V45L+D113T+L149R+V258P+A276S+A364G+S388K;

[0966] V45L+L149R+G187K+V258P+A276S+A364G+S388K;

[0967] M28P+V45L+L149R+V258P+A276S+A364G+S388K;

[0968] V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[0969] A25W+V45L+L149R+S214Q+V258P+A276S;

[0970] V45L+A117S+L149R+S214Q+T215I+V258P+A276S+A364G+S388K;

[0971] A25W+V45L+L149R+V258P+A276S+S388K;

[0972] A25W+V45L+L149R+S214E+H219I+V258P+A276S+A364G;

[0973] V45L+A93S+L149R+V234P+A252S+H334D;

[0974] V45L+L149R+T211H+V258P+A276S+H358T+A364G+S388K;

[0975] A25W+V45L+A117S+L149R+S214E+V258P+A276S+A364G;

[0976] V45L+L149R+S173Y+V258P+A276S+A364G+S388K;

[0977] A25W+V45L+L149R+V258P+A276S+Q314A+A364G;

[0978] V45L+L149R+G187L+V258P+A276S+H358T+A364G;

[0979] V45L+L149R+T215V+V258P+A276S+H358T+A364G;

[0980] V45L+T70R+L149R+V258P+A276S+A364G+S388K;

[0981] V45L+N127D+L149R+V258P+A276S+A364G;

[0982] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Q496R;

[0983] V45L+L149R+W250Y+V258P+A276S+A364G;

[0984] V45L+L149R+V258P+A276S+V350L+H358T+A364G;

[0985] D9E+V45L+L149R+V258P+A276S+H358T+A364G;

[0986] V45L+L149R+T211H+V258P+A276S+H358T+A364G;

[0987] A25W+V45L+L149R+W250Y+A276Q+A364G;

[0988] V45L+L149R+V258P+A276S+L281V+A364G+S388K;

[0989] V45L+L149R+V258P+A276S+S282N+H358T+A364G;

[0990] V45L+L149R+T215I+V258P+A276S+H358T+A364G;

[0991] A25W+V45L+L149R+S173Y+V258P+A276S+A364G;

[0992] V45L+Q61K+L149R+V258P+A276S+A364G+S388K;

[0993] V45L+L149R+T180Q+V258P+A276S+A364G;

[0994] V45L+A117S+L149R+A170S+S214Q+V258P+A276S+A364G+S388K;

[0995] V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[0996] A25W+V45L+L149R+S214E+T215V+V258P+A276S+A364G;

[0997] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V497P;

[0998] V45L+L149R+V258P+A276S+Q314A+A364G;

[0999] V45L+A117S+L149R+V258P+A276S+A364G;

[1000] V45L+A117S+L149R+V258P+A276S+H358T+A364G+S388K;

[1001] V45L+L149R+N168G+V258P+A276S+H358T+A364G+S388K;

[1002] A25W+V45L+Q61K+L149R+V258P+A276S+A364G;

[1003] V45L+L149R+S214E+V258P+A276S+L281V+A364G;

[1004] V45N+L149R+V258P+A276S+A364G+S388K;

[1005] V45L+L149R+V258P+A276S+A286E+H358T+A364G;

[1006] D9E+V45L+L149R+V258P+A276S+A364G+S388K;

[1007] V45L+S92D+L149R+V258P+A276S+A364G+S388K;

[1008] V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K;

[1009] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388H;

[1010] V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K;

[1011] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K;

[1012] A25W+V45L+L149R+S214E+T215I+V258P+A276S+A364G;

[1013] V45L+N127D+L149R+V258P+A276S+H358T+A364G+S388K;

[1014] A25W+V45L+L149R+V258P+A276S+A286E+A364G;

[1015] V45L+L149R+N168G+V258P+A276S+L281V+A364G;

[1016] V45L+Q61R+L149R+V258P+A276S+H358T+A364G;

[1017] V45L+L149R+G187S+V258P+A276S+A364G+S388K;

[1018] V45L+L149R+V258P+A276S+L281V+Q314A+A364G;

[1019] V45L+L149R+V258P+A276S+L281V+H358T+A364G;

[1020] V45L+L149R+A170S+V258P+A276S+H358T+A364G;

[1021] V45L+L149R+A170S+V258P+A276S+A364G+S388K;

[1022] V45L+L149R+T215V+V258P+A276S+A364G+S388K;

[1023] V45L+L149R+V258P+A276Q+L281V+A364G;

[1024] V45L+T70R+A117S+L149R+S214Q+C243S+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1025] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522V;

[1026] A25W+V45L+L149R+V258P+A276S+Q314A;

[1027] V45L+L149R+V258P+A276Q+H358T+A364G+S388K;

[1028] A25W+V45N+L149R+S214E+V258P+A276S+A364G;

[1029] V45L+L149R+V258P+A276S+A286E+A364G;

[1030] V45L+L149R+V258P+A276S+A286S+H358T+A364G;

[1031] A25W+V45L+L149R+G187S+V258P+A276S+A364G;

[1032] V45L+L149R+T180Q+V258P+A276S+L281V+A364G;

[1033] A25W+V45L+L149R+A276Q+L281V+A364G;

[1034] V45L+S92D+L149R+V258P+A276S+L281V+A364G;

[1035] V45L+Q61R+L149R+V258P+A276S+L281V+A364G;

[1036] V45L+L149R+A170S+V258P+A276S+L281V+A364G;

[1037] D11E+A25W+V45L+L149R+V258P+A276S+A364G;

[1038] A25W+V45L+Q61R+L149R+V258P+A276S+A364G;

[1039] A25W+V45L+L149R+T215V+V258P+A276S+A364G;

[1040] D9E+V45L+L149R+V258P+A276S+L281V+A364G;

[1041] A25W+V45L+L149R+V258P+A276S+V350L+A364G;

[1042] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[1043] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V;

[1044] V45L+A117S+L149R+N168G+S214Q+V258P+A276S+A364G+S388K;

[1045] V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[1046] A25W+V45L+L149R+V258P+A276S+A286E;

[1047] A25W+V45L+L149R+V258P+A276S+L281V;

[1048] A25W+V45L+D113T+L149R+V258P+A276S;

[1049] V45L+L149R+H219V+V258P+A276S+L281V+A364G;

[1050] V45L+L149R+T180Q+V258P+A276S+H358T+A364G;

[1051] V45L+L149R+T215V+V258P+A276S+L281V+A364G;

[1052] A25W+V45L+L149R+V258P+A276S+S282N+A364G;

[1053] A25W+V45L+L149R+T215I+V258P+A276S+A364G;

[1054] A25W+V45L+L149R+H219I+V258P+A276S+A364G;

[1055] V45L+A117S+L149R+V258P+A276S+L281V+A364G;

[1056] D9E+A25W+V45L+L149R+V258P+A276S+A364G;

[1057] V45L+L149R+S214Y+V258P+A276S+A364G+S388K;

[1058] A25W+V45L+L149R+T180Q+V258P+A276S+A364G;

[1059] A25W+V45L+L149R+V258P+A276S+L281V+A364G;

[1060] V45L+N127D+L149R+V258P+A276S+L281V+A364G;

[1061] V45L+L149R+S173Y+V258P+A276S+H358T+A364G;

[1062] V45L+Q61R+L149R+V258P+A276S+A364G+S388K;

[1063] M28P+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[1064] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388A;

[1065] V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[1066] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+T477K;

[1067] A25W+V45L+L149R+T180Q+V258P+A276S;

[1068] A25W+V45L+L149R+V258P+A276S+A286S;

[1069] A25W+V45L+L149R+G187S+S214E+V258P+A276S+A364G;

[1070] V45L+L149R+V258P+A276S+L281V+A286E+A364G;

[1071] A25W+V45L+L149R+W250Y+V258P+A276S+A364G;

[1072] A25W+V45L+L149R+V258P+N260H+A276S+A364G;

[1073] V45L+L149R+V258P+A276S+L281V+V350L+A364G;

[1074] A25W+V45L+L149R+A170S+V258P+A276S+A364G;

[1075] V45L+L149R+V258P+A276S+L281V+A286S+A364G;

[1076] V45L+L149R+V258P+A276S+L281V+S282N+A364G;

[1077] D11E+V45L+L149R+V258P+A276S+L281V+A364G;

[1078] V45L+Q61K+L149R+V258P+A276S+L281V+A364G;

[1079] V45L+L149R+T215I+V258P+A276S+L281V+A364G;

[1080] A25W+V45L+S92D+L149R+V258P+A276S+A364G;

[1081] V45L+L149R+S214Y+V258P+A276S+L281V+A364G;

[1082] V45L+L149R+T211H+V258P+A276S+L281V+A364G;

[1083] A25W+V45L+L149R+G187L+V258P+A276S+A364G;

[1084] V45L+S92D+L149R+V258P+A276S+H358T+A364G;

[1085] V45L+L149R+G187L+A276Q+L281V+A364G;

[1086] V45L+L149R+A276Q+L281V+V350L+A364G;

[1087] V45L+L149R+A276Q+L281V+A364G+S388K;

[1088] V45L+A117S+L149R+S214Y+V258P+A276S+A364G+S388K;

[1089] A25W+V45L+S92D+L149R+V258P+A276S;

[1090] A25W+V45L+L149R+G187L+V258P+A276S;

[1091] A25W+V45L+L149R+W250Y+V258P+A276S;

[1092] V45L+D113T+L149R+V258P+A276S+A364G;

[1093] V45L+L149R+G187K+V258P+A276S+H358T+A364G;

[1094] V45L+L149R+N163H+V258P+A276S+L281V+A364G;

[1095] A25W+V45L+T70R+L149R+V258P+A276S+A364G;

[1096] V45L+L149R+S173Y+V258P+A276S+L281V+A364G;

[1097] V45L+L149R+G187L+V258P+A276S+L281V+A364G;

[1098] V45L+L149R+G187K+V258P+A276S+L281V+A364G;

[1099] V45L+L149R+W250Y+V258P+A276S+H358T+A364G;

[1100] V45L+L149R+T211H+V258P+A276S+A364G+S388K;

[1101] V45L+L149R+N163H+V258P+A276S+A364G+S388K;

[1102] V45L+T70R+L149R+A276Q+L281V+A364G;

[1103] V45L+S92D+L149R+A276Q+L281V+A364G;

[1104] V45L+D113T+L149R+A276Q+L281V+A364G;

[1105] V45L+L149R+A276Q+L281V+Q314A+A364G;

[1106] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V;

[1107] A25W+V45L+Q61K+L149R+V258P+A276S;

[1108] D9E+A25W+V45L+L149R+V258P+A276S;

[1109] V45L+T70R+L149R+V258P+A276S+A364G;

[1110] V45L+L149R+V258P+A276S+A286S+A364G+S388K;

[1111] A25W+V45L+L149R+S214Y+V258P+A276S+A364G;

[1112] A25W+V45L+D113T+L149R+V258P+A276S+A364G;

[1113] V45L+T70R+L149R+V258P+A276S+L281V+A364G;

[1114] A25W+V45L+N127D+L149R+V258P+A276S+A364G;

[1115] V45L+T70R+L149R+V258P+A276S+H358T+A364G;

[1116] V45L+L149R+N163H+V258P+A276S+A364G;

[1117] V45L+L149R+T180Q+A276Q+L281V+A364G;

[1118] V45L+L149R+A276Q+L281V+A286S+A364G;

[1119] A25W+V45L+L149R+A170S+V258P+A276S;

[1120] A25W+V45L+T70R+L149R+V258P+A276S;

[1121] A25W+V45L+L149R+S214E+V258P+A276S+A286S+A364G;

[1122] V45L+L149R+V258P+A276S+A286S+H358T+A364G+S388K;

[1123] V45L+L149R+H219I+V258P+A276S+L281V+A364G;

[1124] A25W+V45L+A117S+L149R+V258P+A276S+A364G;

[1125] A25W+V45L+L149R+N168G+V258P+A276S+A364G;

[1126] V45L+L149R+N168G+A276Q+L281V+A364G;

[1127] V45L+L149R+S173Y+A276Q+L281V+A364G;

[1128] V45L+L149R+W250Y+A276Q+L281V+A364G;

[1129] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K;

[1130] A25W+V45L+L149R+A276Q+A286E+A364G;

[1131] A25W+V45L+L149R+A276Q+A364G+S388K;

[1132] V45L+N127D+L149R+V258P+A276S+H358T+A364G;

[1133] A25W+V45L+L149R+V258P+A276S;

[1134] V45L+N127D+L149R+A276Q+L281V+A364G;

[1135] V45L+L149R+A276Q+L281V+A286E+A364G;

[1136] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V500T;

[1137] A25W+V45L+A117S+L149R+V258P+A276S;

[1138] A25W+V45L+L149R+H219V+V258P+A276S+A364G;

[1139] V45L+L149R+S173Y+V258P+A276S+H358T+A364G+S388K;

[1140] D11E+V45L+L149R+V258P+A276S+H358T+A364G;

[1141] V45L+A79C+L149R+V258P+A276S+N355G+A364G+S388K;

[1142] A24K+V45L+L149R+V258P+A276S+A364G;

[1143] V45L+L149R+V258P+A276S+S282N+A364G;

[1144] V45L+A117S+L149R+A276Q+L281V+A364G;

[1145] V45L+L149R+N260H+A276Q+L281V+A364G;

[1146] V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K;

[1147] A25W+V45L+L149R+N168G+V258P+A276S;

[1148] A25W+V45L+L149R+G187S+V258P+A276S;

[1149] A25W+V45L+L149R+V258P+A276S+V350L;

[1150] A25W+V45L+Q61R+L149R+V258P+A276S;

[1151] A25W+V45L+L149R+G187L+S214E+V258P+A276S+A364G;

[1152] V45L+L149R+G187S+V258P+A276S+L281V+A364G;

[1153] A25W+V45L+L149R+N163H+V258P+A276S+A364G;

[1154] A25W+V45L+L149R+G187K+V258P+A276S+A364G;

[1155] V45N+L149R+V258P+A276S+L281V+A364G;

[1156] V45L+L149R+A276Q+L281V+A364G;

[1157] V45L+L149R+V258P+N260H+A276S+H358T+A364G;

[1158] V45L+L149R+A276Q+S282N+A364G;

[1159] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A364G+S388K;

[1160] A25W+V45L+L149R+V258P+A276S+S282N;

[1161] A25W+V45L+L149R+S173Y+V258P+A276S;

[1162] A25W+V45L+L149R+A276Q+A286S+A364G;

[1163] V45L+D113T+L149R+V258P+A276S+L281V+A364G;

[1164] V45L+L149R+S214Q+V258P+A276S+L281V+A364G+S388K;

[1165] V45L+D113T+L149R+V258P+A276S+H358T+A364G;

[1166] A25W+V45L+L149R+T215V+V258P+A276S;

[1167] V45L+L149R+N168G+V258P+A276S+H358T+A364G;

[1168] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A472L;

[1169] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S473K;

[1170] A25W+V45L+L149R+T215I+V258P+A276S;

[1171] A25W+V45L+L149R+T211H+V258P+A276S; <h2 style=";text-align:left;direction:ltr">

[1172] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+V258P+A276Q;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1173] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+S214Q+T215V+V258P+A276S+A364G+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1174] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+N163H+V258P+A276S+H358T+A364G+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1175] <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A499L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1176] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+V258P+A276S+V350L+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1177] <h2 style=";text-align:left;direction:ltr"> V45L+A79C+A117S+L149R+V258P+A276S+A364G+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1178] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+D113T+L149R+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1179] <h2 style=";text-align:left;direction:ltr"> A25W+V45N+L149R+V258P+A276S+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1180] <h2 style=";text-align:left;direction:ltr"> V45L+T70R+L149R+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1181] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+H219I+V258P+A276S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1182] <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V498I;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1183] <h2 style=";text-align:left;direction:ltr"> M28P+V45L+L149R+V258P+A276S+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1184] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+T70R+L149R+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1185] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276Q+Q314A+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1186] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A170S+V258P+A276S+H358T+A364G+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1187] A25W+V45L+L149R+S214Y+V258P+A276S;

[1188] V45L+L149R+S214Y+V258P+A276S+H358T+A364G;

[1189] V45L+L149R+A276Q+L281V+H358T+A364G;

[1190] A25W+V45L+L149R+H219V+V258P+A276S;

[1191] V45L+A117S+L149R+N163H+S214Q+V258P+A276S+A364G+S388K;

[1192] D11E+A25W+V45L+L149R+V258P+A276S;

[1193] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N527H;

[1194] A25W+V45L+A117S+L149R+A276Q+A364G;

[1195] V45L+L149R+V258P+L281V+A364G;

[1196] A25W+V45L+L149R+G187L+A276Q+A364G;

[1197] V45N+L149R+V258P+A276S+H358T+A364G;

[1198] V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T+R483V;

[1199] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+D470T+R483V;

[1200] A25W+V45L+L149R+A276Q+A364G;

[1201] <h2 style=";text-align:left;direction:ltr">V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497E;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1202] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+N163H+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1203] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+S173Y+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1204] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276Q+S282N+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1205] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276Q+H358T+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1206] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+T180Q+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1207] <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+V258P+A276S+H358T+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1208] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276Q+Q314A+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1209] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+G187K+V258P+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1210] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276Q+A286E+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1211] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+N127D+L149R+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1212] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A170S+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1213] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+N127D+L149R+V258P+A276S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1214] <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+T477V;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1215] <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G503L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1216] A25W+M28P+V45L+L149R+V258P+A276S+A364G;

[1217] V45L+L149R+A276Q+H358T+A364G;

[1218] A25W+V45L+L149R+N168G+A276Q+A364G;

[1219] A25W+V45L+L149R+N260H+A276Q+A364G;

[1220] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+A364G+S388K;

[1221] V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1222] V45L+A117S+L149R+S214Q+T215K+V258P+A276S+A364G+S388K;

[1223] A25W+V45L+L149R+G187K+V258P+A276S;

[1224] A25W+M28P+V45L+L149R+V258P+A276S;

[1225] A25W+V45N+L149R+V258P+A276S;

[1226] V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T;

[1227] V45L+N127D+L149R+A276Q+A364G;

[1228] V45L+L149R+W250Y+A276Q+A364G;

[1229] V45L+L149R+W250Y+V258P+A364G;

[1230] V45L+L149R+N163H+A276Q+L281V+A364G;

[1231] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q385C+S388K;

[1232] A25W+V45L+L149R+S214E+T215K+V258P+A276S+A364G;

[1233] M28P+V45L+L149R+V258P+A276S+L281V+A364G;

[1234] V45L+L149R+A276Q+A364G+S388K;

[1235] A25W+V45L+L149R+V258P+A364G;

[1236] M28P+V45L+L149R+V258P+A276S+H358T+A364G;

[1237] V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K;

[1238] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540V;

[1239] V45L+L149R+N168G+A276Q+A364G;

[1240] V45L+A117S+L149R+A276Q+A364G;

[1241] V45L+L149R+N163H+V258P+A276S+H358T+A364G;

[1242] V45L+L149R+T215K+V258P+A276S+H358T+A364G;

[1243] A24K+V45L+L149R+A276Q+A364G;

[1244] V45L+L149R+A276Q+A286S+A364G;

[1245] V45L+L149R+V258P+A364G;

[1246] <h2 style=";text-align:left;direction:ltr">V45L+L149R+H219I+V258P+A276S+A364G+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1247] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A170S+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1248] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+T180Q+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1249] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276Q+V350L+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1250] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+V258P+S282N+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1251] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1252] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276S+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1253] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+T215K+V258P+A276S+A364G+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1254] <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+N355G+A364G+S388K+D470T;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1255] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+V258P+A276S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1256] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276S+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1257] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+G187S+V258P+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1258] <h2 style=";text-align:left;direction:ltr"> V45L+S92D+L149R+V258P+A276S+H358T+A364G+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1259] <h2 style=";text-align:left;direction:ltr"> A25W+L149R+V258P+A276S+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1260] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+G187L+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1261] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+V258P+A276S+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1262] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+N260H+A276Q+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1263] V45L+L149R+W250Y+V258R+A364G;

[1264] V45L+L149R+N163H+A276Q+A364G;

[1265] V45L+S92D+L149R+A276Q+A364G;

[1266] V45L+L149R+S173Y+A276Q+A364G;

[1267] V45L+S92D+L149R+V258P+A364G;

[1268] V45L+L149R+W250Y+V258P+A276S+L281V+A364G;

[1269] V45L+L149R+L281V+A364G;

[1270] V45L+D113T+L149R+A276Q+A364G;

[1271] L149R+V258P+A276S+A364G;

[1272] V45L+L149R+G187S+V258R+A364G;

[1273] V45L+V258P+A276S+A364G;

[1274] V45L+L149R+V258R+A364G+S388K;

[1275] A25W+V45L+L149R+A364G;

[1276] V45L+L149R+G187K+V258R+A364G;

[1277] V45L+L149R+V258P;

[1278] V45L+L149R+V258R+S282N+A364G;

[1279] V45L+L149R;

[1280] V45L+L149R+V258R+L281V+A364G;

[1281] V45L+L149R+A364G;

[1282] V45L+L149R+S214Q+V258P+A276S+N355G+A364G+S388K;

[1283] V45L+S92N+L149R+V258P+A364G;

[1284] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K;

[1285] A25W+V45L+L149R+S214E+V258P+A276S+N355G+A364G;

[1286] V45L+L149R+G187L+V258P+A276S+A364G;

[1287] V45L+L149R+V258R+A364G;

[1288] V45L+L149R+V258P+A364G+S388K;

[1289] A25W+V45L+L149R+A276Q+V350L+A364G;

[1290] V45L+L149R+H219V+V258P+A276S+A364G+S388K;

[1291] V45L+L149R+G187K+A364G;

[1292] V45L+L149R+G187S+A364G;

[1293] V45L+A117S+L149R+S214Q+V258P+A276S+N355G+A364G+S388K;

[1294] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Y386G+S388K+D470T+R483V;

[1295] V45L+L149R+W250Y;

[1296] V45L+S92N+L149R+V258R+A364G;

[1297] A25W+V45L+L149R+V258P+A276S+N355G+A364G;

[1298] V45L+L149R+V258P+A276S+N355G+A364G+S388K;

[1299] V45L+L149R+G187S;

[1300] V45N+L149R;

[1301] V45L+L149R+S282N;

[1302] L149R+A364G;

[1303] Y386G;

[1304] V258P+A276Q;

[1305] V258P+A276S;

[1306] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D+D470T+R483V;

[1307] A25W+L149R;

[1308] V45L+A276S;

[1309] V45L+S92D+L149R;

[1310] A25W+A276S;

[1311] Q385C;

[1312] V45L+L149R+W250Y+A364G;

[1313] V45L+A276Q;

[1314] V45L+V258P;

[1315] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Y386G+S388K;

[1316] A25W+V258P;

[1317] A25W+A276Q;

[1318] L149R+W250Y;

[1319] V45L+L149R+V258P+A276S+L281V+N355G+A364G; <h2 style=";text-align:left;direction:ltr">

[1320] <h2 style=";text-align:left;direction:ltr"> V45L+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1321] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+V258P+A276S+N355G+H358T+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1322] <h2 style=";text-align:left;direction:ltr"> V45L+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1323] <h2 style=";text-align:left;direction:ltr"> V45N+V258P;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1324] <h2 style=";text-align:left;direction:ltr"> A276S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1325] <h2 style=";text-align:left;direction:ltr"> V258P+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1326] <h2 style=";text-align:left;direction:ltr"> A25W+V45L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1327] <h2 style=";text-align:left;direction:ltr"> A276Q+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1328] <h2 style=";text-align:left;direction:ltr"> A276C;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1329] <h2 style=";text-align:left;direction:ltr"> A276Q;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1330] <h2 style=";text-align:left;direction:ltr"> A276F;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1331] <h2 style=";text-align:left;direction:ltr"> W250Y+A276Q;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1332] <h2 style=";text-align:left;direction:ltr"> A79C;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1333] <h2 style=";text-align:left;direction:ltr"> A276S+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1334] <h2 style=";text-align:left;direction:ltr"> A276Q+L281V;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1335] <h2 style=";text-align:left;direction:ltr"> V45L+L149R+V258P+A276S+N355G+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1336] <h2 style=";text-align:left;direction:ltr"> A276N;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1337] <h2 style=";text-align:left;direction:ltr"> W250Y+A276S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1338] <h2 style=";text-align:left;direction:ltr"> A25W+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1339] <h2 style=";text-align:left;direction:ltr"> A276S+L281V;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1340] <h2 style=";text-align:left;direction:ltr"> G187S+A276Q;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1341] <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+V258P+A276S+N355G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1342] <h2 style=";text-align:left;direction:ltr"> V45L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1343] <h2 style=";text-align:left;direction:ltr"> S92D+A276S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1344] <h2 style=";text-align:left;direction:ltr"> S19T;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1345] <h2 style=";text-align:left;direction:ltr"> L149R+V258R;

[1346] V45N+S388K;

[1347] A25W+V45L+S92D+L149R+A276Q+A364G;

[1348] V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S501E

[1349] H358D;

[1350] A25W+A364G;

[1351] V258P+L281V;

[1352] L149R;

[1353] V45L+L149R+H219V+V258P+A276S+H358T+A364G;

[1354] A25W;

[1355] V258R+A276S;

[1356] V45N;

[1357] G187S+A276S;

[1358] G187K+A276S;

[1359] I469T;

[1360] V45L+S92D;

[1361] V45L+L281V;

[1362] V45N+W250Y;

[1363] V258R+A276Q;

[1364] V45L+V258R;

[1365] W250Y+S388K;

[1366] A25W+V45L+L149R+A276Q+N355G+A364G;

[1367] V45N+G187K;

[1368] A25W+V45L+L149R+S214E+V258P+A276S+Q314A+A364G; <h2 style=";text-align:left;direction:ltr">

[1369] <h2 style=";text-align:left;direction:ltr"> S388A;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1370] <h2 style=";text-align:left;direction:ltr"> A276T;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1371] <h2 style=";text-align:left;direction:ltr"> A25W+V258R;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1372] <h2 style=";text-align:left;direction:ltr"> G187K+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1373] <h2 style=";text-align:left;direction:ltr"> A25W+S92D;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1374] <h2 style=";text-align:left;direction:ltr"> L281V+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1375] <h2 style=";text-align:left;direction:ltr"> V45N+V258R;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1376] <h2 style=";text-align:left;direction:ltr"> S388H;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1377] <h2 style=";text-align:left;direction:ltr"> S92D;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1378] <h2 style=";text-align:left;direction:ltr"> D525L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1379] <h2 style=";text-align:left;direction:ltr"> S214Q;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1380] <h2 style=";text-align:left;direction:ltr"> L281V+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1381] <h2 style=";text-align:left;direction:ltr"> A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1382] <h2 style=";text-align:left;direction:ltr"> S388L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1383] <h2 style=";text-align:left;direction:ltr"> S388R;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1384] <h2 style=";text-align:left;direction:ltr"> S473G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1385] <h2 style=";text-align:left;direction:ltr"> S92D+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1386] <h2 style=";text-align:left;direction:ltr"> A25W+G187S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1387] <h2 style=";text-align:left;direction:ltr"> A25W+G187K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1388] <h2 style=";text-align:left;direction:ltr"> W250Y+V258P;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1389] <h2 style=";text-align:left;direction:ltr"> S92D+V258P;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1390] <h2 style=";text-align:left;direction:ltr"> S389V;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1391] <h2 style=";text-align:left;direction:ltr"> A20H;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1392] <h2 style=";text-align:left;direction:ltr"> W495E;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1393] <h2 style=";text-align:left;direction:ltr"> G187K+W250Y;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1394] <h2 style=";text-align:left;direction:ltr"> Y386Y;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1395] <h2 style=";text-align:left;direction:ltr"> V393H;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1396] <h2 style=";text-align:left;direction:ltr"> G187L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1397] <h2 style=";text-align:left;direction:ltr"> Q61K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1398] <h2 style=";text-align:left;direction:ltr">V45N+S92D;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1399] <h2 style=";text-align:left;direction:ltr"> G187S+A364G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1400] <h2 style=";text-align:left;direction:ltr"> G187S+L281V;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1401] <h2 style=";text-align:left;direction:ltr"> G187S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1402] <h2 style=";text-align:left;direction:ltr"> A286E;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1403] <h2 style=";text-align:left;direction:ltr"> A276Y;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1404] <h2 style=";text-align:left;direction:ltr"> V258P;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1405] <h2 style=";text-align:left;direction:ltr"> Q496E;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1406] <h2 style=";text-align:left;direction:ltr"> G394A;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1407] <h2 style=";text-align:left;direction:ltr"> V393R;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1408] <h2 style=";text-align:left;direction:ltr"> G187S+S388K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1409] <h2 style=";text-align:left;direction:ltr"> T366V;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1410] <h2 style=";text-align:left;direction:ltr"> S389S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1411] <h2 style=";text-align:left;direction:ltr"> S92N;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1412] <h2 style=";text-align:left;direction:ltr"> N527H;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1413] <h2 style=";text-align:left;direction:ltr"> Q384A;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1414] <h2 style=";text-align:left;direction:ltr"> V497D;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1415] <h2 style=";text-align:left;direction:ltr"> D470T;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1416] <h2 style=";text-align:left;direction:ltr"> A18V;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1417] <h2 style=";text-align:left;direction:ltr"> Q496Q;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1418] <h2 style=";text-align:left;direction:ltr"> Q496R;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1419] <h2 style=";text-align:left;direction:ltr"> S214E;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1420] <h2 style=";text-align:left;direction:ltr"> P362P;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1421] <h2 style=";text-align:left;direction:ltr"> S389H;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1422] <h2 style=";text-align:left;direction:ltr"> V258R;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1423] <h2 style=";text-align:left;direction:ltr"> A276D;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1424] <h2 style=";text-align:left;direction:ltr"> L281V;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1425] <h2 style=";text-align:left;direction:ltr"> V45I;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1426] <h2 style=";text-align:left;direction:ltr"> A117C;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1427] <h2 style=";text-align:left;direction:ltr"> N395N;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1428] <h2 style=";text-align:left;direction:ltr"> Y391Y;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1429] <h2 style=";text-align:left;direction:ltr"> A24H;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1430] <h2 style=";text-align:left;direction:ltr"> A472I;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1431] <h2 style=";text-align:left;direction:ltr"> D470K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1432] <h2 style=";text-align:left;direction:ltr"> S473K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1433] <h2 style=";text-align:left;direction:ltr"> S473S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1434] <h2 style=";text-align:left;direction:ltr"> W495I;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1435] <h2 style=";text-align:left;direction:ltr"> V497E;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1436] <h2 style=";text-align:left;direction:ltr"> A24K;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1437] <h2 style=";text-align:left;direction:ltr"> V45T;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1438] <h2 style=";text-align:left;direction:ltr"> L471R;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1439] <h2 style=";text-align:left;direction:ltr"> A472L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1440] <h2 style=";text-align:left;direction:ltr"> A20P;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1441] <h2 style=";text-align:left;direction:ltr"> N395D;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1442] <h2 style=";text-align:left;direction:ltr"> G394D;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1443] <h2 style=";text-align:left;direction:ltr"> G394Q;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1444] <h2 style=";text-align:left;direction:ltr"> G187S+V258R;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1445] <h2 style=";text-align:left;direction:ltr"> S92D+G187S;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1446] <h2 style=";text-align:left;direction:ltr"> V45C;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1447] <h2 style=";text-align:left;direction:ltr"> N476N;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1448] <h2 style=";text-align:left;direction:ltr"> G207G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1449] <h2 style=";text-align:left;direction:ltr"> A364A;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1450] <h2 style=";text-align:left;direction:ltr"> D470A;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1451] <h2 style=";text-align:left;direction:ltr"> N474G;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">

[1452] D470V; and wherein the variant has xylanase activity, and wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100% sequence identity to SEQ ID NO: 1, and wherein the variants have increased thermostability as measured by TSA as an increased melting temperature of at least 0.5°C compared to the xylanase of SEQ ID NO: 1.

[1453] In one aspect, the present invention is directed to xylanase variants comprising at least one of the following substitutions or combinations of substitutions:

[1454] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[1455] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394Q+D470T+R483V;

[1456] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V;

[1457] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[1458] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[1459] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V;

[1460] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[1461] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V;

[1462] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[1463] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[1464] V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V;

[1465] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1466] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1467] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1468] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1469] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1470] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1471] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1472] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1473] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R;

[1474] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1475] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1476] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1477] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1478] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+L530R;

[1479] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R;

[1480] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R;

[1481] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+R483V+L530R;

[1482] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R;

[1483] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+R483V+L530R;

[1484] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V;

[1485] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A286E+H358D+A364G+Q384A+S388K+N395D+D470T+R483V;

[1486] V45L+A117S+L149R+G187K+S214E+T215I+V258P+A276S+A286E+H358D+A364G+S388K+V393H+D470T+R483V;

[1487] V45L+A117S+L149R+G187K+S214E+T215I+V258P+A276S+A286E+H358D+A364G+S388K+N395D+D470T+R483V;

[1488] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T+R483V;

[1489] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1490] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V;

[1491] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+R483V;

[1492] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366I+S388K+D470T+R483V;

[1493] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1494] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T+L530R;

[1495] V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1496] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1497] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T+R483V;

[1498] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T+R483V;

[1499] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T+L530R;

[1500] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T+R483V;

[1501] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1502] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468V+D470T+R483V;

[1503] V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T;

[1504] V45L+A79C+L149R+S214E+V258P+A276S+A364G+S388K;

[1505] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1506] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T+R483V;

[1507] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1508] V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+L530R;

[1509] V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1510] V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1511] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T+R483V;

[1512] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T+L530R;

[1513] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T+L530R;

[1514] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T+L530R;

[1515] V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T+R483V;

[1516] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T+R483V;

[1517] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D+R483V;

[1518] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T+R483V;

[1519] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K+R483V;

[1520] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496R;

[1521] V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468A+D470T+R483V;

[1522] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+W495E;

[1523] V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T+L530R;

[1524] V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1525] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Y391V+D470T+R483V;

[1526] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1527] D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1528] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V+R483V;

[1529] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476N+R483V;

[1530] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R+D470T+R483V;

[1531] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480L+L530R;

[1532] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A+L530R;

[1533] V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1534] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481S+R483V;

[1535] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1536] V45L+T70R+A117S+L149R+S214Q+C243V+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V;

[1537] V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1538] D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1539] V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T+L530R

[1540] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D+L530R;

[1541] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T+R483V;

[1542] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496Q;

[1543] V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T+R483V;

[1544] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496E;

[1545] V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1546] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T+L530R;

[1547] V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T+L530R;

[1548] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P+R483V;

[1549] A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1550] V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1551] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484K;

[1552] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N474G+L530R;

[1553] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T+L530R;

[1554] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T+R483V;

[1555] V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1556] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484S;

[1557] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1558] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484D;

[1559] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S528H;

[1560] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S501N;

[1561] V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1562] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+A499L;

[1563] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1564] V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T+R483V;

[1565] V45L+A79C+L149R+S214Q+V258P+A276S+A364G+S388K;

[1566] V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T+L530R;

[1567] V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T+L530R;

[1568] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481S+L530R;

[1569] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496E+L530R;

[1570] V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1571] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V498I+L530R;

[1572] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A+R483V;

[1573] V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V;

[1574] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+A499Y;

[1575] V45L+A79C+L149R+V258P+A276S+Q314A+A364G+S388K;

[1576] V45L+A79C+L149R+V258P+A276S+L281V+A364G+S388K;

[1577] V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T+L530R;

[1578] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501N+L530R;

[1579] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476N+L530R;

[1580] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V+L530R;

[1581] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+D470T+L530R;

[1582] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N+L530R;

[1583] V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R;

[1584] V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500V+L530R;

[1585] V45L+A117S+L149R+S214Q+V2...

Claims

1. A xylanase variant of a parent xylanase, the xylanase variant comprising substitutions at two positions corresponding to positions 45 and 149 of SEQ ID NO: 1, and wherein the variant has xylanase activity, and wherein the variant is based on the polypeptide of SEQ ID NO: 1 and the substitutions consist of any one of the following combinations of substitutions: V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V; V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394Q+D470T+R483V; V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+G394A+D470T+R483V; V45L+Q61K+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+Q384A+S388K+V393H+D470T+R483V; V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+L530R; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+L530R; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+R483V+L530R; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A286E+H358D+A364G+Q384A+S388K+V393H+D470T+R483V; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A286E+H358D+A364G+Q384A+S388K+N395D+D470T+R483V; V45L+A117S+L149R+G187K+S214E+T215I+V258P+A276S+A286E+H358D+A364G+S388K+V393H+D470T+R483V; V45L+A117S+L149R+G187K+S214E+T215I+V258P+A276S+A286E+H358D+A364G+S388K+N395D+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T+R483V; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A79C+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366I+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T+L530R; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T+R483V; D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468V+D470T+R483V; V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T V45L+A79C+L149R+S214E+V258P+A276S+A364G+S388K; V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T+R483V; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496R; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+W495E; V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Y391V+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480L+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A+L530R; V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A+R483V; V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+T70R+A117S+L149R+S214Q+C243V+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+Q496E; V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P+R483V; A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484K V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N474G+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T+R483V; V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484S; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L484D; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S528H; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S501N; V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+A499L; V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T+R483V; V45L+A79C+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496E+L530R; V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V498I+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A+R483V; V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+A499Y; V45L+A79C+L149R+V258P+A276S+Q314A+A364G+S388K; V45L+A79C+L149R+V258P+A276S+L281V+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501N+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N+L530R; V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V500T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+S501E; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+D525L+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G526T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N527H+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K+L530R; M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501E+L530R; V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499L+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A472I+L530R; V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+N527H; V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497P; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V498I; V45L+A79C+L149R+S173Y+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N+R483V; V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T+L530R; M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A79C+L149R+G187K+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H+D470T+L530R; V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388L+D470T+R483V; V45L+Q61R+A79C+L149R+V258P+A276S+A364G+S388K; V45L+A79C+L149R+N168G+V258P+A276S+A364G+S388K; V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A79C+L149R+T215V+V258P+A276S+A364G+S388K; V45L+A79C+L149R+V258P+A276S+A286S+A364G+S388K; V45L+A79C+L149R+H219V+V258P+A276S+A364G+S388K; V45L+A79C+L149R+A170S+V258P+A276S+A364G+S388K; V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+D95N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A+D470T; V45L+A79C+L149R+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A+D470T+R483V; V45L+A93T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499Y; V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N; V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K+D470T; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468L+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366I+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S473G; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478P; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q384A+S388K+D470T+R483V; D11E+V45L+A79C+L149R+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N529T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q+D470T; V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A79C+L149R+V258P+A276S+A286E+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+G503L; V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K+D470T; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388R+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S528H; V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496R; V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K+D470T; D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S473K; V45L+A79C+L149R+T180Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388R+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K+D470T+R483V; V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+N260H+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+G187S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N474G; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501N; V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R+D470T; V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+D470T; V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+G187S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480N; V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A79C+L149R+H219I+V258P+A276S+A364G+S388K; V45L+L149R+S214E+V258P+A276S+H358D+A364G+D470T; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366V+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R+D470T+R483V; V45N+A79C+L149R+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q+D470T+R483V; V45L+A79C+L149R+V258P+A276S+V350L+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366I+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+G526T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L484S; V45L+A79C+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A499L; V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T+L530R; V45L+A79C+D113T+L149R+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+D525L; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V498I; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388L+D470T; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S528H+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476D+R483V; D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S501E; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+S481A; V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+I469T+D470T+R483V; V45L+A79C+N127D+L149R+V258P+A276S+A364G+S388K; D9E+V45L+A79C+L149R+V258P+A276S+A364G+S388K; V45L+A117S+L149R+G187L+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N529T+L530R; V45L+A79C+L149R+W250Y+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V497P; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N527H; V45L+A117S+L149R+N168G+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477V+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478N+R483V; V45L+A117S+L149R+S214E+V258P+A276S+A364G+S388K+D470T+R483V; M28P+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H+D470T+R483V; V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V497P; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V498I; V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K+D470T+L530R; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375V+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470A+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477K+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+Q496E; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+Q496R; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+A499L; V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C468S+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276Q+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G503L+L530R; V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+N476D; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+S501E; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+N529T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+S501N; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S481A+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478P+R483V; D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T477V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V497P+L530R; V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K+D470T+R483V; V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+N527H; V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K+D470T; V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388H+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H+D470T+R483V; V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A79C+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+Q496E; V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V+D470T; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+H219I+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A79C+L149R+N163H+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+A499Y; V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V500T; V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+V500T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G526T; V45L+C60L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+C69L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497D; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+D525L; V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q384A+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H+D470T; V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N476D; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L478N+R483V; V45L+C60A+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D+D470T; A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+T70R+A117S+L149R+S214Q+C243L+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478N; V45L+C60S+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K+D470T+R483V; V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+G187L+S214Q+V258P+A276S+A364G+S388K+D470T; D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G; V45L+C69A+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+T70R+A117S+L149R+C161S+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+S282N+A364G+S388K+D470T; V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+D95N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S473G; V45L+T70R+D95N+A117S+L149R+S214Q+V258P+A276S+L356M+H358D+A364G+S388K; D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394D+D470T; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+G503L; V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470A; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+L478P; V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K+D470T; V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+C69V+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+D525L; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+Q496R; V45L+A117S+N127D+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+A499Y; V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+T480L; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388L+D470T; V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+N529T; V45L+C60V+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V497E; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+L478N; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; M28P+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276Q+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470V+R483V; V45L+A117S+L149R+S214Y+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N395D; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T477K; V45L+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K; V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+T215I+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+Q496E; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+W495I; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V498I; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470K+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V500T; D11E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+A170S+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T477V; A25W+V45L+A79C+L149R+S214E+V258P+A276S+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394Q; V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K+D470T; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375A+S388K+G394A+D470T+R483V; V45L+A117S+L149R+D192E+S214Q+V258P+A276S+H358D+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+A472L; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+A499Y; V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q385C+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388A+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388H+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T480N; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+V497P; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+A499L; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S501N; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q384A+S388K; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375S+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388L+D470T+R483V; V45L+A79C+S92D+L149R+V258P+A276S+A364G+S388K; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540A; V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394A; V45L+C69S+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V498I; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G; V45L+A117S+L149R+S214Q+H219I+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+N163H+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+L149R+S214Q+V258P+A276S+H358D+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+H358D+A364G+S388K; V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214E+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D; A25W+V45L+A79C+L149R+V258P+A276S+A364G; V45L+L149R+S214Q+V258P+A276S+A286E+A364G+S388K; V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+T366V+S388K; V45L+A117S+L149R+D192E+S214Q+V258P+A276S+H358D+A364G; V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+T215I+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+H358D+A364G+S388K; V45L+L149R+S214Q+T215I+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N476D; V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+T215K+V258P+A276S+A364G+S388K+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T477V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+L478P; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S481A; A25W+V45L+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T+R483V; V45L+A79C+L149R+V258P+A276S+L281V+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V500T; V45L+A117S+L149R+S214Q+V258P+A276S+V350L+H358D+A364G+S388K; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+C375L+S388K+G394A+D470T+R483V; V45L+L149R+A170S+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214E+V258P+A276S+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470V+R483V; V45L+Q61K+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+L149R+N168G+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A79C+D95D+L149R+V258P+A276S+A364G+S388K; V45L+Q77E+A79C+L149R+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+V497W; V45L+L149R+S214Q+V258P+A276S+S282N+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388R; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540L; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522S; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+W495S; V45L+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K; V45L+D113T+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497W; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540S; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396S+D470T+R483V; V45L+T70R+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+N474G; V45L+A117S+L149R+S214Q+V258P+A276S+S282N+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V+D470T; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S501E; A25W+V45L+L149R+S214E+V258P+A276S+A364G; V45L+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K; V45L+L149R+G187K+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S473K; V45L+A117S+L149R+G187L+S214Q+V258P+A276S+H358D+A364G+S388K; C40L+V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Q496E; A25W+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+L149R+V258P+A276S+L281V+H358T+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388A; V45L+A117S+L149R+N168G+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389H; M28P+V45L+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+T480L; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q384A+S388K; V45L+A93S+L149R+A252S+H334D; C40A+V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+L149R+G187L+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Q385C+S388K; V45L+L149R+S214Q+V258P+A276S+A286S+A364G+S388K; V45L+S92D+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388L; V45L+A117S+L149R+S214Q+V258P+A276S+A286E+A364G+S388K; D9E+V45L+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+A170S+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+Y391V; V45L+A117S+L149R+S214Q+V258P+A276S+L281V+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394D; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S473G; V45L+A79C+L149R+V258P+A276S+H358T+A364G+S388K; V45L+L149R+S214Q+V258P+A276Q+A364G+S388K; A25W+V45L+L149R+S214E+V258P+A276S+H358T+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T480N; D9E+V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+H219I+V258P+A276S+H358D+A364G+S388K; C40S+V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; C40V+V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; A25W+V45L+L149R+S214E+V258P+A276S+A286E+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394A; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+A499L; A25W+V45L+Q61K+L149R+S214E+V258P+A276S+A364G; V45L+A117S+L149R+S214Q+T215V+V258P+A276S+H358D+A364G+S388K; A25W+V45L+L149R+V258P+A276S+H358T+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+R483V+W495E; A25W+V45L+A79C+L149R+V258P+A276S; V45L+L149R+S214Q+V258P+A276S+V350L+A364G+S388K; D11E+V45L+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+L149R+H219I+V258P+A276S+H358T+A364G+S388K; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396V+D470T+R483V; V45N+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+H219V+V258P+A276S+H358D+A364G+S388K; V45N+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+S92D+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+L149R+V258P+A276S+H358T+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+L478P; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S481A; V45L+A117S+L149R+S214Q+V258P+A276S+Q314A+A364G+S388K; A25W+V45L+L149R+T211H+S214E+V258P+A276S+A364G; A25W+V45L+L149R+S214E+H219V+V258P+A276S+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+S389V; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393H; V45L+A117S+L149R+S214Q+V258P+A276Q+H358D+A364G+S388K; V45L+A117S+N127D+L149R+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+L149R+W250Y+V258P+A276S+H358T+A364G+S388K; D9E+V45L+L149R+V258P+A276S+H358T+A364G+S388K; V45L+L149R+H219V+V258P+A276S+H358T+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+A472L; A25W+V45L+L149R+V258P+A276S+A364G; V45L+A117S+L149R+G187K+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+L478N; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393R; V45L+A117S+L149R+S214E+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366V+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358T+A364G+S388K; D11E+A25W+V45L+L149R+S214E+V258P+A276S+A364G; V45L+T70R+A117S+L149R+C161V+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+A117S+L149R+T211H+S214Q+V258P+A276S+H358D+A364G+S388K; V45L+L149R+V258P+A276S+Q314A+H358T+A364G+S388K; D11E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G394Q; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N395D; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V393H; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S501E; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S528H; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388L; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+C396L+D470T+R483V; V45L+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K; V45L+D113T+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+T480L; V45L+A93S+L149R+V234P+A252S; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H; A25W+V45L+Q61R+L149R+S214E+V258P+A276S+A364G; V45L+A117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389H; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+T366I+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N474G; A25W+V45L+L149R+S214E+V258P+A276S+L281V+A364G; D9E+A25W+V45L+L149R+S214E+V258P+A276S+A364G; V45L+A117S+L149R+S214Q+T215K+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Y+V258P+A276S+H358D+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+V393R; V45L+Q61R+L149R+V258P+A276S+H358T+A364G+S388K; V45L+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+D113T+L149R+V258P+A276S+H358T+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A286S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388R; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A499Y; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V500T; V45L+Q61R+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+L149R+S214E+V258P+A276S+H358T+A364G; V45L+A117S+L149R+S214Q+V258P+A276Q+A364G+S388K; V45L+L149R+V258P+A276S+L281V+A364G; V45L+A117S+L149R+S214Q+W250Y+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+T480N; V45L+A117S+L149R+G187S+S214Q+V258P+A276S+A364G+S388K; A25W+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; A25W+V45L+L149R+S214E+V258P+A276Q+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N476D; V45L+L149R+S214Q+V258P+A276S+L281V+A364G; V45L+A93S+L149R+A252S+H334D+A340G; V45L+L149R+A252S+H334D; V45L+N127D+L149R+V258P+A276S+A364G+S388K; V45L+L149R+V258P+A276S+H358T+A364G+S388K; V45L+L149R+V258P+A276S+A364G+S388K; D9E+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+L149R+N168G+V258P+A276S+A364G; V45L+L149R+T180Q+V258P+A276S+H358T+A364G+S388K; V45L+L149R+G187L+V258P+A276S+A364G+S388K; V45L+L149R+W250Y+V258P+A276S+A364G+S388K; V45L+L149R+V258P+A276S+A286E+A364G+S388K; V45L+L149R+V258P+A276S+S282N+A364G+S388K; A25W+V45L+L149R+V258P+A276S+A364G+S388K; V45L+L149R+S214Q+V258P+A276S+H358T+A364G; V45L+L149R+S173Y+V258P+A276S+A364G; V45L+A117S+L149R+S214Q+H219V+V258P+A276S+A364G+S388K; V45L+A93S+L149R+A252S+H334D+A340G; V45L+L149R+S190E+D446T+R459V; A25W+V45L+L149R+V258P+A276S+H358T; A25W+V45L+S92D+L149R+S214E+V258P+A276S+A364G; A25W+V45L+L149R+S214E+V258P+A276S+V350L+A364G; A25W+V45L+L149R+S214Q+V258P+A276S+A364G; V45L+L149R+N168G+V258P+A276S+A364G+S388K; V45L+A117S+L149R+V258P+A276S+A364G+S388K; A25W+V45L+L149R+V258P+A276S+H358T+A364G; V45L+L149R+V258P+N260H+A276S+A364G+S388K; V45L+L149R+T215I+V258P+A276S+A364G+S388K; A25W+V45L+L149R+V258P+A276Q+A364G; V45L+T70R+A117S+L149R+C161L+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; A25W+V45L+L149R+S214E+V258P+A276S; V45L+A117S+L149R+S214Q+V258P+A276S+A286S+H358D+A364G+S388K; V45L+L149R+T211H+S214Q+V258P+A276S+A364G+S388K; V45L+Q61K+L149R+V258P+A276S+H358T+A364G; V45L+L149R+V258P+A276S+Q314A+H358T+A364G; V45L+L149R+T180Q+V258P+A276S+A364G+S388K; V45L+L149R+V258P+A276S+Q314A+A364G+S388K; A25W+V45L+L149R+V258P+A276S+A286S+A364G; V45L+L149R+S190E+D446T; V45L+L149R+V258P+A276S+A364G; V45L+L149R+A170S+V258P+A276S+A364G; V45L+L149R+V258P+A276Q+A364G; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522A; V45L+L149R+H219I+V258P+A276S+H358T+A364G; V45L+L149R+V258P+A276S+V350L+A364G+S388K; D11E+V45L+L149R+V258P+A276S+A364G+S388K; V45L+D113T+L149R+V258P+A276S+A364G+S388K; V45L+L149R+G187K+V258P+A276S+A364G+S388K; M28P+V45L+L149R+V258P+A276S+A364G+S388K; V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V; A25W+V45L+L149R+S214Q+V258P+A276S; V45L+A117S+L149R+S214Q+T215I+V258P+A276S+A364G+S388K; A25W+V45L+L149R+V258P+A276S+S388K; A25W+V45L+L149R+S214E+H219I+V258P+A276S+A364G; V45L+A93S+L149R+V234P+A252S+H334D; V45L+L149R+T211H+V258P+A276S+H358T+A364G+S388K; A25W+V45L+A117S+L149R+S214E+V258P+A276S+A364G; V45L+L149R+S173Y+V258P+A276S+A364G+S388K; A25W+V45L+L149R+V258P+A276S+Q314A+A364G; V45L+L149R+G187L+V258P+A276S+H358T+A364G; V45L+L149R+T215V+V258P+A276S+H358T+A364G; V45L+T70R+L149R+V258P+A276S+A364G+S388K; V45L+N127D+L149R+V258P+A276S+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Q496R; V45L+L149R+W250Y+V258P+A276S+A364G; V45L+L149R+V258P+A276S+V350L+H358T+A364G; D9E+V45L+L149R+V258P+A276S+H358T+A364G; V45L+L149R+T211H+V258P+A276S+H358T+A364G; A25W+V45L+L149R+W250Y+A276Q+A364G; V45L+L149R+V258P+A276S+L281V+A364G+S388K; V45L+L149R+V258P+A276S+S282N+H358T+A364G; V45L+L149R+T215I+V258P+A276S+H358T+A364G; A25W+V45L+L149R+S173Y+V258P+A276S+A364G; V45L+Q61K+L149R+V258P+A276S+A364G+S388K; V45L+L149R+T180Q+V258P+A276S+A364G; V45L+A117S+L149R+A170S+S214Q+V258P+A276S+A364G+S388K; V45L+Q61R+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; A25W+V45L+L149R+S214E+T215V+V258P+A276S+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V497P; V45L+L149R+V258P+A276S+Q314A+A364G; V45L+A117S+L149R+V258P+A276S+A364G; V45L+A117S+L149R+V258P+A276S+H358T+A364G+S388K; V45L+L149R+N168G+V258P+A276S+H358T+A364G+S388K; A25W+V45L+Q61K+L149R+V258P+A276S+A364G; V45L+L149R+S214E+V258P+A276S+L281V+A364G; V45N+L149R+V258P+A276S+A364G+S388K; V45L+L149R+V258P+A276S+A286E+H358T+A364G; D9E+V45L+L149R+V258P+A276S+A364G+S388K; V45L+S92D+L149R+V258P+A276S+A364G+S388K; V45L+A117S+L149R+T180Q+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388H; V45L+A117S+L149R+S214Q+T215V+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+V350L+A364G+S388K; A25W+V45L+L149R+S214E+T215I+V258P+A276S+A364G; V45L+N127D+L149R+V258P+A276S+H358T+A364G+S388K; A25W+V45L+L149R+V258P+A276S+A286E+A364G; V45L+L149R+N168G+V258P+A276S+L281V+A364G; V45L+Q61R+L149R+V258P+A276S+H358T+A364G; V45L+L149R+G187S+V258P+A276S+A364G+S388K; V45L+L149R+V258P+A276S+L281V+Q314A+A364G; V45L+L149R+V258P+A276S+L281V+H358T+A364G; V45L+L149R+A170S+V258P+A276S+H358T+A364G; V45L+L149R+A170S+V258P+A276S+A364G+S388K; V45L+L149R+T215V+V258P+A276S+A364G+S388K; V45L+L149R+V258P+A276Q+L281V+A364G; V45L+T70R+A117S+L149R+S214Q+C243S+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C522V; A25W+V45L+L149R+V258P+A276S+Q314A; V45L+L149R+V258P+A276Q+H358T+A364G+S388K; A25W+V45N+L149R+S214E+V258P+A276S+A364G; V45L+L149R+V258P+A276S+A286E+A364G; V45L+L149R+V258P+A276S+A286S+H358T+A364G; A25W+V45L+L149R+G187S+V258P+A276S+A364G; V45L+L149R+T180Q+V258P+A276S+L281V+A364G; A25W+V45L+L149R+A276Q+L281V+A364G; V45L+S92D+L149R+V258P+A276S+L281V+A364G; V45L+Q61R+L149R+V258P+A276S+L281V+A364G; V45L+L149R+A170S+V258P+A276S+L281V+A364G; D11E+A25W+V45L+L149R+V258P+A276S+A364G; A25W+V45L+Q61R+L149R+V258P+A276S+A364G; A25W+V45L+L149R+T215V+V258P+A276S+A364G; D9E+V45L+L149R+V258P+A276S+L281V+A364G; A25W+V45L+L149R+V258P+A276S+V350L+A364G; V45L+Q61K+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+Y391V; V45L+A117S+L149R+N168G+S214Q+V258P+A276S+A364G+S388K; V45L+D113T+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; A25W+V45L+L149R+V258P+A276S+A286E; A25W+V45L+L149R+V258P+A276S+L281V; A25W+V45L+D113T+L149R+V258P+A276S; V45L+L149R+H219V+V258P+A276S+L281V+A364G; V45L+L149R+T180Q+V258P+A276S+H358T+A364G; V45L+L149R+T215V+V258P+A276S+L281V+A364G; A25W+V45L+L149R+V258P+A276S+S282N+A364G; A25W+V45L+L149R+T215I+V258P+A276S+A364G; A25W+V45L+L149R+H219I+V258P+A276S+A364G; V45L+A117S+L149R+V258P+A276S+L281V+A364G; D9E+A25W+V45L+L149R+V258P+A276S+A364G; V45L+L149R+S214Y+V258P+A276S+A364G+S388K; A25W+V45L+L149R+T180Q+V258P+A276S+A364G; A25W+V45L+L149R+V258P+A276S+L281V+A364G; V45L+N127D+L149R+V258P+A276S+L281V+A364G; V45L+L149R+S173Y+V258P+A276S+H358T+A364G; V45L+Q61R+L149R+V258P+A276S+A364G+S388K; M28P+V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388A; V45N+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+T477K; A25W+V45L+L149R+T180Q+V258P+A276S; A25W+V45L+L149R+V258P+A276S+A286S; A25W+V45L+L149R+G187S+S214E+V258P+A276S+A364G; V45L+L149R+V258P+A276S+L281V+A286E+A364G; A25W+V45L+L149R+W250Y+V258P+A276S+A364G; A25W+V45L+L149R+V258P+N260H+A276S+A364G; V45L+L149R+V258P+A276S+L281V+V350L+A364G; A25W+V45L+L149R+A170S+V258P+A276S+A364G; V45L+L149R+V258P+A276S+L281V+A286S+A364G;V45L+L149R+V258P+A276S+L281V+S282N+A364G; D11E+V45L+L149R+V258P+A276S+L281V+A364G; V45L+Q61K+L149R+V258P+A276S+L281V+A364G; V45L+L149R+T215I+V258P+A276S+L281V+A364G; A25W+V45L+S92D+L149R+V258P+A276S+A364G; V45L+L149R+S214Y+V258P+A276S+L281V+A364G; V45L+L149R+T211H+V258P+A276S+L281V+A364G; A25W+V45L+L149R+G187L+V258P+A276S+A364G; V45L+S92D+L149R+V258P+A276S+H358T+A364G; V45L+L149R+G187L+A276Q+L281V+A364G; V45L+L149R+A276Q+L281V+V350L+A364G; V45L+L149R+A276Q+L281V+A364G+S388K; V45L+A117S+L149R+S214Y+V258P+A276S+A364G+S388K;A25W+V45L+S92D+L149R+V258P+A276S; A25W+V45L+L149R+G187L+V258P+A276S; A25W+V45L+L149R+W250Y+V258P+A276S; V45L+D113T+L149R+V258P+A276S+A364G; V45L+L149R+G187K+V258P+A276S+H358T+A364G; V45L+L149R+N163H+V258P+A276S+L281V+A364G; A25W+V45L+T70R+L149R+V258P+A276S+A364G; V45L+L149R+S173Y+V258P+A276S+L281V+A364G; V45L+L149R+G187L+V258P+A276S+L281V+A364G; V45L+L149R+G187K+V258P+A276S+L281V+A364G; V45L+L149R+W250Y+V258P+A276S+H358T+A364G; V45L+L149R+T211H+V258P+A276S+A364G+S388K; V45L+L149R+N163H+V258P+A276S+A364G+S388K; V45L+T70R+L149R+A276Q+L281V+A364G; V45L+S92D+L149R+A276Q+L281V+A364G; V45L+D113T+L149R+A276Q+L281V+A364G; V45L+L149R+A276Q+L281V+Q314A+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S389V; A25W+V45L+Q61K+L149R+V258P+A276S; D9E+A25W+V45L+L149R+V258P+A276S; V45L+T70R+L149R+V258P+A276S+A364G; V45L+L149R+V258P+A276S+A286S+A364G+S388K; A25W+V45L+L149R+S214Y+V258P+A276S+A364G; A25W+V45L+D113T+L149R+V258P+A276S+A364G; V45L+T70R+L149R+V258P+A276S+L281V+A364G; A25W+V45L+N127D+L149R+V258P+A276S+A364G; V45L+T70R+L149R+V258P+A276S+H358T+A364G; V45L+L149R+N163H+V258P+A276S+A364G; V45L+L149R+T180Q+A276Q+L281V+A364G; V45L+L149R+A276Q+L281V+A286S+A364G; A25W+V45L+L149R+A170S+V258P+A276S; <h2 style=";text-align:left;direction:ltr">A25W+V45L+T70R+L149R+V258P+A276S; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+S214E+V258P+A276S+A286S+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+V258P+A276S+A286S+H358T+A364G+S388K; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+H219I+V258P+A276S+L281V+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+A117S+L149R+V258P+A276S+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+N168G+V258P+A276S+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+N168G+A276Q+L281V+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+S173Y+A276Q+L281V+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+W250Y+A276Q+L281V+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S173Y+S214Q+V258P+A276S+A364G+S388K; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276Q+A286E+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276Q+A364G+S388K; <h2 style=";text-align:left;direction:ltr"> V45L+N127D+L149R+V258P+A276S+H358T+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+V258P+A276S; <h2 style=";text-align:left;direction:ltr"> V45L+N127D+L149R+A276Q+L281V+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276Q+L281V+A286E+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+A117S+L149R+V258P+A276S; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+H219V+V258P+A276S+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+S173Y+V258P+A276S+H358T+A364G+S388K; <h2 style=";text-align:left;direction:ltr"> D11E+V45L+L149R+V258P+A276S+H358T+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+A79C+L149R+V258P+A276S+N355G+A364G+S388K; <h2 style=";text-align:left;direction:ltr"> A24K+V45L+L149R+V258P+A276S+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+V258P+A276S+S282N+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+A276Q+L281V+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+N260H+A276Q+L281V+A364G; V45L+A117S+L149R+T211H+S214Q+V258P+A276S+A364G+S388K; A25W+V45L+L149R+N168G+V258P+A276S; A25W+V45L+L149R+G187S+V258P+A276S; A25W+V45L+L149R+V258P+A276S+V350L; A25W+V45L+Q61R+L149R+V258P+A276S; A25W+V45L+L149R+G187L+S214E+V258P+A276S+A364G; V45L+L149R+G187S+V258P+A276S+L281V+A364G; A25W+V45L+L149R+N163H+V258P+A276S+A364G; A25W+V45L+L149R+G187K+V258P+A276S+A364G; V45N+L149R+V258P+A276S+L281V+A364G; V45L+L149R+A276Q+L281V+A364G; V45L+L149R+V258P+N260H+A276S+H358T+A364G; V45L+L149R+A276Q+S282N+A364G; V45L+S92D+A117S+L149R+S214Q+V258P+A276S+A364G+S388K; A25W+V45L+L149R+V258P+A276S+S282N; A25W+V45L+L149R+S173Y+V258P+A276S; A25W+V45L+L149R+A276Q+A286S+A364G; V45L+D113T+L149R+V258P+A276S+L281V+A364G; V45L+L149R+S214Q+V258P+A276S+L281V+A364G+S388K; V45L+D113T+L149R+V258P+A276S+H358T+A364G; A25W+V45L+L149R+T215V+V258P+A276S; V45L+L149R+N168G+V258P+A276S+H358T+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A472L; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+S473K; A25W+V45L+L149R+T215I+V258P+A276S; A25W+V45L+L149R+T211H+V258P+A276S; A25W+V45L+L149R+V258P+A276Q; V45L+L149R+S214Q+T215V+V258P+A276S+A364G+S388K; V45L+L149R+N163H+V258P+A276S+H358T+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+A499L; V45L+L149R+V258P+A276S+V350L+A364G; V45L+A79C+A117S+L149R+V258P+A276S+A364G+S388K; A25W+V45L+D113T+L149R+A276Q+A364G; A25W+V45N+L149R+V258P+A276S+A364G; V45L+T70R+L149R+A276Q+A364G; A25W+V45L+L149R+H219I+V258P+A276S; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+V498I; M28P+V45L+L149R+V258P+A276S+A364G; A25W+V45L+T70R+L149R+A276Q+A364G; A25W+V45L+L149R+A276Q+Q314A+A364G; V45L+L149R+A170S+V258P+A276S+H358T+A364G+S388K; A25W+V45L+L149R+S214Y+V258P+A276S; V45L+L149R+S214Y+V258P+A276S+H358T+A364G; V45L+L149R+A276Q+L281V+H358T+A364G; A25W+V45L+L149R+H219V+V258P+A276S; V45L+A117S+L149R+N163H+S214Q+V258P+A276S+A364G+S388K; D11E+A25W+V45L+L149R+V258P+A276S; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+N527H; A25W+V45L+A117S+L149R+A276Q+A364G; V45L+L149R+V258P+L281V+A364G; <h2 style=";text-align:left;direction:ltr">A25W+V45L+L149R+G187L+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> V45N+L149R+V258P+A276S+H358T+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T+R483V; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388H+D470T+R483V; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+R483V+V497E; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+N163H+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+S173Y+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276Q+S282N+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A276Q+H358T+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+T180Q+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+V258P+A276S+H358T+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276Q+Q314A+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+G187K+V258P+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276Q+A286E+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+N127D+L149R+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+A170S+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+N127D+L149R+V258P+A276S; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+T477V; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+G503L; <h2 style=";text-align:left;direction:ltr"> A25W+M28P+V45L+L149R+V258P+A276S+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+L149R+A276Q+H358T+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+N168G+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> A25W+V45L+L149R+N260H+A276Q+A364G; <h2 style=";text-align:left;direction:ltr"> V45L+A117S+L149R+G187L+S214Q+V258P+A276S+A364G+S388K; V45L+A117S+L149R+N163H+S214Q+V258P+A276S+H358D+A364G+S388K+D470T+L530R; V45L+A117S+L149R+S214Q+T215K+V258P+A276S+A364G+S388K; A25W+V45L+L149R+G187K+V258P+A276S; A25W+M28P+V45L+L149R+V258P+A276S; A25W+V45N+L149R+V258P+A276S; V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K+D470T; V45L+N127D+L149R+A276Q+A364G; V45L+L149R+W250Y+A276Q+A364G; V45L+L149R+W250Y+V258P+A364G; V45L+L149R+N163H+A276Q+L281V+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+Q385C+S388K; A25W+V45L+L149R+S214E+T215K+V258P+A276S+A364G; M28P+V45L+L149R+V258P+A276S+L281V+A364G; V45L+L149R+A276Q+A364G+S388K; A25W+V45L+L149R+V258P+A364G; M28P+V45L+L149R+V258P+A276S+H358T+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+N355G+H358D+A364G+S388K; V45L+T70R+A117S+L149R+S214Q+V258P+A276S+L281V+H358D+A364G+S388K+G394A+D470T+R483V+C540V; V45L+L149R+N168G+A276Q+A364G; V45L+A117S+L149R+A276Q+A364G; V45L+L149R+N163H+V258P+A276S+H358T+A364G; V45L+L149R+T215K+V258P+A276S+H358T+A364G; A24K+V45L+L149R+A276Q+A364G; V45L+L149R+A276Q+A286S+A364G; V45L+L149R+V258P+A364G; V45L+L149R+H219I+V258P+A276S+A364G+S388K; V45L+L149R+A170S+A276Q+A364G; V45L+L149R+T180Q+A276Q+A364G; V45L+L149R+A276Q+V350L+A364G; V45L+L149R+V258P+S282N+A364G; V45L+L149R+A276Q+A364G; V45L+L149R+A276S+A364G; V45L+L149R+T215K+V258P+A276S+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+N355G+A364G+S388K+D470T; V45L+L149R+V258P+A276S; A25W+V45L+L149R+A276S+A364G; V45L+L149R+G187S+V258P+A364G; V45L+S92D+L149R+V258P+A276S+H358T+A364G+S388K; V45L+L149R+G187L+A276Q+A364G; V45L+L149R+N260H+A276Q+A364G; V45L+L149R+W250Y+V258R+A364G; V45L+L149R+N163H+A276Q+A364G; V45L+S92D+L149R+A276Q+A364G; V45L+L149R+S173Y+A276Q+A364G; V45L+S92D+L149R+V258P+A364G; V45L+L149R+W250Y+V258P+A276S+L281V+A364G; V45L+L149R+L281V+A364G; V45L+D113T+L149R+A276Q+A364G; V45L+L149R+G187S+V258R+A364G; V45L+L149R+V258R+A364G+S388K; A25W+V45L+L149R+A364G; V45L+L149R+G187K+V258R+A364G; V45L+L149R+V258P; V45L+L149R+V258R+S282N+A364G; V45L+L149R; V45L+L149R+V258R+L281V+A364G; V45L+L149R+A364G; V45L+L149R+S214Q+V258P+A276S+N355G+A364G+S388K; V45L+S92N+L149R+V258P+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A286E+H358D+A364G+S388K; A25W+V45L+L149R+S214E+V258P+A276S+N355G+A364G; V45L+L149R+G187L+V258P+A276S+A364G; V45L+L149R+V258R+A364G; V45L+L149R+V258P+A364G+S388K; A25W+V45L+L149R+A276Q+V350L+A364G; V45L+L149R+H219V+V258P+A276S+A364G+S388K; V45L+L149R+G187K+A364G; V45L+L149R+G187S+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+N355G+A364G+S388K; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Y386G+S388K+D470T+R483V; V45L+L149R+W250Y; V45L+S92N+L149R+V258R+A364G; A25W+V45L+L149R+V258P+A276S+N355G+A364G; V45L+L149R+V258P+A276S+N355G+A364G+S388K; V45L+L149R+G187S; V45N+L149R; V45L+L149R+S282N; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+S388K+G394D+D470T+R483V; V45L+S92D+L149R; V45L+L149R+W250Y+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+H358D+A364G+Y386G+S388K; V45L+L149R+V258P+A276S+L281V+N355G+A364G; V45L+L149R+V258P+A276S+N355G+H358T+A364G; V45L+L149R+V258P+A276S+N355G+A364G; A25W+V45L+L149R+V258P+A276S+N355G; A25W+V45L+S92D+L149R+A276Q+A364G; V45L+A117S+L149R+S214Q+V258P+A276S+A364G+S388K+D470T+S501E; V45L+L149R+H219V+V258P+A276S+H358T+A364G; A25W+V45L+L149R+A276Q+N355G+A364G; A25W+V45L+L149R+S214E+V258P+A276S+Q314A+A364G; And wherein the xylanase variant has increased thermostability compared to the xylanase of SEQ ID NO:

1.

2. The xylanase variant of claim 1, wherein the increased thermostability is an increased melting temperature of 0.5°C or greater as measured using TSA.

3. A polynucleotide encoding the xylanase variant according to claim 1 or 2. A nucleic acid construct comprising the polynucleotide according to claim 3 . An expression vector comprising the polynucleotide according to claim 3 . A host cell comprising the polynucleotide according to claim 3 . The host cell of claim 6 , wherein the host cell is a yeast cell. The host cell of claim 7 , wherein the host cell is a yeast cell.

9. The host cell of claim 8, wherein the host cell is a Saccharomyces cerevisiae cell.

10. A method of producing the xylanase variant of claim 1 or 2, comprising cultivating the host cell of any one of claims 6-9 under conditions conducive for production of the polypeptide and further comprising recovering the polypeptide.

11. A composition comprising the xylanase variant of claim 1 or 2.

12. A method for increasing starch yield and / or gluten yield of corn kernels in a wet milling process, the method comprising contacting a fiber-rich fraction of the corn kernels with an effective amount of the xylanase variant of claim 1 or 2 and optionally one or more hydrolytic enzymes.

13. The method according to claim 12, comprising the steps of: a) soaking the corn kernels in water to produce soaked kernels; b) milling the soaked kernels to produce milled kernels; c) separating the germ from the milled kernels to produce a corn kernel material comprising fiber, starch, and gluten; as well as d) subjecting the corn kernel material to a fiber washing process to separate starch and gluten from the fiber; Wherein at least one xylanase variant as claimed in claim 1 or 2 is present / added before or during step d).

14. The method of claim 13, further comprising the steps of: e) separating the starch from the gluten; and optionally f) washing the starch.

15. The method of any one of claims 12-14, wherein the one or more hydrolases comprise one or more cellulases.

16. The method of claim 15, wherein the one or more cellulases comprise one or more enzymes selected from the group consisting of endoglucanase (EG) and cellobiohydrolase (CBH).

17. Use of the xylanase variant of claim 1 or 2 to increase starch yield and / or gluten yield of corn kernels in a wet milling process.

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