α-Amylase variants and polynucleotides encoding same

Abstract

The present invention relates to α-amylase variants of a parent α-amylase, wherein the α-amylase variants have improved cleaning performance compared to the parent α-amylase. The invention also relates to compositions comprising the variants of the invention, uses of the variants, and methods for producing the variants.

Description

[Technical Field]

[0001] Sequence Listing Reference This application contains a Sequence Listing in computer readable form, which is incorporated herein by reference.

[0002] The present invention relates to α-amylase variants, polynucleotides encoding the variants, methods for producing the variants, and methods for using these variants. [Background technology]

[0003] Alpha-amylases (alpha-1,4-glucan-4-glucanohydrolases, EC 3.2.1.1) are a group of enzymes that hydrolyze starch, glycogen, and other related polysaccharides by cleaving internal alpha-1,4-glycosidic bonds. They have been used for many years, for example, in laundry, where alpha-amylases are well known for their beneficial effects on the removal of starch-containing or starch-based stains. However, in other commercial applications, these enzymes have become important in the initial stages of starch processing (liquefaction), fabric desizing, alcohol production, etc., as well as as cleaning agents in detergent compositions.

[0004] In recent years, there has been a desire to improve the properties of various amylases. In particular, the goal of lowering laundry temperatures to reduce energy consumption has become a major focus for the household goods sector. Therefore, much effort has been devoted to finding improved α-amylase variants.

[0005] Nevertheless, there remains a need for α-amylase variants that have altered properties and offer improved performance in various industrial applications. Accordingly, the present invention provides such further improved α-amylase variants with improved properties compared to their parents. Summary of the Invention [Problem to be solved by the invention]

[0006] It is an object of the present invention to provide polypeptides having α-amylase activity (α-amylases) with improved cleaning performance, in particular for use in automatic washing machines and / or dishwashers. [Means for solving the problem]

[0007] The present invention identifies the amino acid sequence of a nucleotide sequence of interest, using SEQ ID NO: 1 for numbering, at positions: H1, H2, G7, I9, Q11, N16, N19, N25, A37, W43, W48, N54, V56, Y58, G59, A60, L63, T81, E84, E86, R90, Q98, V104, G109, A111, F113, R116, Q118, Q125, R127, E130, S132, G133, T134, Y135, Q136, A139, G142, N144, G149, R158, Y160, D163, W167, Q169, S170, R171, Q1 72, L173, A174, N175, R176, Y178, R181, G182, A186, W187, N195, M202, Y 203, A204, V206, D209, H210, E212, T227, L235, V238, M246, Q256, K259, V 264, A265, E266, Y267, K269, N270, L272, G273, A274, L275, E276, W284, M286, V291, L293, Y295, Y298, Q299, N302, S303, S304, N306, R310, N311, α-amylase variants of a parent α-amylase comprising modifications at one or more positions corresponding to N314, G315, L317, Q319, R320, S323, F328, G337, A339, Q345, D357, Q365, P377, D375, Q385, K391, Q395, R400, D406, W408, V410, S431, G435, W439, R444, Q445, R458, N465, Q466, W469, F473, G476 and V481, wherein the variant has α-amylase activity, and has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% but less than 100% sequence identity to the polypeptides of SEQ ID NOs: 1 to 17, and said variants have improved cleaning performance compared to said parent α-amylase, and said parent α-amylase has the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

[0008] The invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of producing the variants.

[0009] The present invention also relates to a method for improving the cleaning performance of a parent α-amylase. DETAILED DESCRIPTION OF THE INVENTION

[0010] definition In accordance with this Detailed Description, the following definitions apply: It should be noted that the singular forms "a," "an," and "the" include plural referents unless the context clearly requires otherwise.

[0011] As used herein, the term "about" in front of a value or parameter includes the aspect of the value or parameter itself. For example, the expression "about X" includes the aspect "X."

[0012] Unless otherwise defined or clearly indicated by 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.

[0013] The term "α-amylase" is synonymous with the term "polypeptide having α-amylase activity." The term "α-amylase activity" refers to the activity of α-1,4-glucan-4-glucanohydrolases (EC 3.2.1.1), which constitute a group of enzymes that catalyze the hydrolysis of starch and other linear and branched 1,4-glycosidic oligosaccharides and polysaccharides. Accordingly, the term "α-amylase" as used herein refers to enzymes (enzyme class; EC 3.2.1.1) with α-amylase activity that hydrolyze the α-linkages of large α-linked polysaccharides, such as starch and glycogen, to yield glucose and maltose. The terms "α-amylase" and "amylase" are used interchangeably herein and may have the same meaning and purpose. For purposes of the present invention, α-amylase activity is determined according to the procedure described below under the subheading "Methods." In one aspect, the α-amylase of the invention has at least 20%, e.g., at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 100% of the α-amylase activity of one or more of the polypeptides of SEQ ID NOs: 1-17.

[0014] As used herein, the term "amino acid" refers to the 20 standard genetically encoded amino acids and their corresponding "d" stereoisomers (as compared to the natural "l" form), omega-amino acids, other naturally occurring amino acid sequences, non-standard 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 a side chain functional group. Such derivatized molecules include, for example, molecules in which a free amino group is derivatized to form an amine hydrochloride salt, p-toluenesulfonyl, carboxybenzoxy, t-butyloxycarbonyl, chloroacetyl, or formyl groups. 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 20 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, so long as the required activity is maintained. Other included modifications are amidation, amino-terminal acylation (e.g., acetylation or thioglycolic acid amidation), terminal carboxylation (e.g., ammonia or methylamine), and similar terminal modifications.

[0015] When an amino acid is specifically recited, such as "alanine" or "Ala" or "A," the term refers to both l-alanine and d-alanine unless otherwise specified. Other non-standard amino acids may also be suitable components of the polypeptides of the invention, so long as the desired functional properties are retained by the polypeptide. For the peptides shown, each encoded amino acid residue is represented, where appropriate, by the one-letter code corresponding to the trivial name of the standard amino acid. In one embodiment, the polypeptides of the invention comprise or consist of l-amino acids.

[0016] The term "catalytic domain" refers to the region of an enzyme that contains the enzyme's catalytic machinery.

[0017] The term "cDNA" refers to a DNA molecule that can be produced by reverse transcription from a mature, spliced, mRNA molecule obtained from a eukaryotic 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 emerging as the mature, spliced mRNA.

[0018] The term "coding sequence" refers to a polynucleotide that directly specifies the amino acid sequence of its polypeptide product. The boundaries of the coding sequence are generally determined by an open reading frame, which usually begins with the ATG start codon or alternative start codons such as GTG and TTG and ends with a stop codon such as TAA, TAG, and TGA. A coding sequence can be a DNA, cDNA, synthetic, or recombinant polynucleotide.

[0019] The term "control sequences" refers to all components necessary for the expression of a polynucleotide encoding a variant of the present invention. Each control sequence may be native or foreign to the polynucleotide encoding the variant, or native or foreign to each other. Such control sequences include, but are not limited to, a leader, polyadenylation sequence, propeptide sequence, promoter, signal peptide sequence, and transcription terminator. At a minimum, control sequences include a promoter, and transcriptional and translational stop signals. Control sequences may be provided with linkers for the purpose of introducing specific restriction sites facilitating ligation of the control sequences with the coding region of the polynucleotide encoding the variant.

[0020] As used herein, the term "corresponding to" refers to a method of determining a particular amino acid position in a sequence, where a particular amino acid sequence is referenced. For example, for purposes of the present invention, when a particular amino acid position is referenced, one of skill in the art can determine which particular amino acid may be associated in another amino acid sequence by aligning the other amino acid sequence with the referenced amino acid sequence. Alignments of another amino acid sequence with, for example, the sequence set forth in SEQ ID NO: 1, or any other sequence listed herein, are described elsewhere herein. Alignments of another amino acid sequence with, for example, the sequence set forth in SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or any other sequence listed herein are described elsewhere herein. Alternative alignment methods may be used and are well known to those of skill in the art.

[0021] As used herein, the term "dishwashing composition" refers to any form of composition for cleaning hard surfaces. The present invention is not limited to any particular type of dishwashing composition or any particular detergent. Thus, in one embodiment, the dishwashing composition is a liquid dishwashing composition, a powder dishwashing composition, and optionally, the composition may be in the form of a unit dose.

[0022] As used herein, the term "enzymatic detergent benefits" refers to the beneficial effects that enzymes can impart to a detergent compared to the same detergent without enzymes. Important cleaning benefits that enzymes can provide include soil removal with little or no visible soiling after washing and / or cleaning, prevention or reduction of redeposition of soils released during the washing process (an effect also known as anti-redeposition), and complete or partial restoration of whiteness to fabrics that were initially white but have acquired a grayish or yellowish appearance after repeated use and washing (an effect also known as whitening). Fabric care benefits are also important to enzyme detergency benefits, although they are not directly related to catalytic soil removal or prevention of soil redeposition. Examples of such fabric care benefits are prevention or reduction of dye transfer from one fabric to another or to another part of the same fabric (an effect also known as dye transfer or backstain prevention), reduced pilling tendency or removal of loose or cut fibers from the fabric surface to remove existing pills or fuzz (an effect also known as anti-pilling), improved fabric softness, brighter fabric color, and removal of particulate soils lodged within the fibers of fabrics or garments. Enzymatic bleaching is yet another enzyme detergency benefit, where catalytic activity is generally used to catalyze the formation of bleaching components such as hydrogen peroxide or other peroxides.

[0023] As used herein, the term "expression" refers to any step involved in the production of a variant, including but not limited to transcription, post-transcriptional modification, translation, post-translational modification, and secretion.

[0024] As used herein, the term "expression vector" refers to a linear or circular DNA molecule that contains a polynucleotide encoding a variant and is operably linked to a control sequence that provides for its expression.

[0025] The term "fragment" refers to a polypeptide having one or more (several) amino acids deleted from the amino and / or carboxyl terminus of the mature polypeptide; wherein the fragment has α-amylase activity.

[0026] The term "highly stringent conditions" refers to 12-24 hours of standard Southern blotting, for probes at least 100 nucleotides in length, followed by prehybridization and hybridization in 5x SSPE, 0.3% SDS, 200 micrograms / ml fragment-treated and denatured salmon sperm DNA, and 50% formamide at 42° C. The carrier material is finally washed three times, 15 minutes each time, with 2x SSC, 0.2% SDS at 65° C.

[0027] The term "hard surface cleaning" as used herein refers to cleaning of hard surfaces, where hard surfaces may include floors, tables, walls, etc., as well as surfaces of hard articles such as automobiles (auto-washing) and dishes (dishwashing). Dishwashing includes, but is not limited to, cleaning cutlery such as plates, cups, glasses, bowls, spoons, knives, forks, kitchen utensils, ceramic, plastic, metal, porcelain, glass, and acrylic products.

[0028] The term "improved property" is defined herein as a characteristic associated with a variant that is improved relative to the parent α-amylase. Such improved properties include, but are not limited to, increased amylolytic activity, improved catalytic efficiency, improved catalytic rate, improved chemical stability, improved oxidative stability, improved pH activity, improved pH stability, increased relative specific activity, increased specific activity, increased substrate binding, increased substrate cleavage, increased substrate specificity, improved substrate stability, improved surface properties, increased thermal activity, improved heat resistance, improved soil removal performance, e.g., performance on starch-containing soils, improved cleaning performance, such as stain removal and graying prevention, stability, e.g., thermal stability, pH stability, or stability in the presence of builders, including chelating agents, stability in powder, liquid, or gel detergent formulations or dishwashing compositions, temperature-dependent performance and activity profile, pH activity, substrate specificity, product specificity, and chemical stability. The improved property can be any of the properties defined and described herein, such as cleaning performance.

[0029] The term "improved cleaning performance" is defined herein to refer to an alteration in the cleaning performance of an amylase of the invention relative to the cleaning performance of the parent α-amylase of SEQ ID NO: 1 or SEQ ID NO: 2. This alteration can be seen, for example, as improved soil removal. Cleaning performance is improved if the Improvement Factor (IF) is at least 1.1, at least 1.2, or at least 1.3.

[0030] As used herein, the term "isolated" refers to a substance that is present in a form or environment that does not occur in nature. Non-limiting examples of isolated substances include: (1) any substance that does not occur in nature; (2) any substance that is at least partially removed from one or more or all of the natural components with which it is naturally associated, including, but not limited to, any enzyme, mutant, nucleic acid, protein, peptide, or cofactor; (3) any substance that has been artificially modified relative to a naturally occurring substance; 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., multiple copies of the gene encoding the substance; use of a stronger promoter than that naturally associated with the gene encoding the substance). An isolated substance may be present in a fermentation broth sample.

[0031] The term "isolated polynucleotide" refers to a polynucleotide that has been artificially modified. In one embodiment, an isolated polynucleotide is at least 1% pure, e.g., at least 5% pure, at least 10% pure, at least 20% pure, at least 40% pure, at least 60% pure, at least 80% pure, at least 90% pure, and at least 95% pure, as measured by agarose gel electrophoresis. The polynucleotide can be of genomic, cDNA, RNA, semisynthetic, synthetic origin, or any combination thereof.

[0032] As used herein, the term "mature polypeptide" refers to a polypeptide in its final form following translation and any post-translational modifications, such as N-terminal processing, C-terminal truncation, glycosylation, phosphorylation, etc. It is known in the art that a host cell can produce a mixture of two or more different mature polypeptides (i.e., having different C-terminal and / or N-terminal amino acids) expressed by the same polynucleotide.

[0033] As used herein, the term "mature polypeptide coding sequence" refers to a polynucleotide that encodes a mature polypeptide having α-amylase activity.

[0034] In the context of the polypeptides of the present invention, the term "modified" means that one or more amino acids in a reference amino acid sequence (i.e., SEQ ID NO: 1 or 2) are altered by substitution with a different amino acid, by insertion of an amino acid, or by deletion, preferably at least two deletions. The terms "modified," "altered," and "mutated" may be used interchangeably and constitute the same meaning and purpose.

[0035] The term "moderately stringent conditions" refers to 12-24 hours of standard Southern blotting for probes at least 100 nucleotides in length, followed by prehybridization and hybridization in 5x SSPE, 0.3% SDS, 200 micrograms / ml fragment-treated and denatured salmon sperm DNA, and 35% formamide at 42° C. The carrier material is finally washed three times, for 15 minutes each, with 2x SSC, 0.2% SDS at 55° C.

[0036] The term "moderately stringent conditions" refers to 12-24 hours of standard Southern blotting for probes at least 100 nucleotides in length, followed by prehybridization and hybridization in 5x SSPE, 0.3% SDS, 200 micrograms / ml fragment-treated and denatured salmon sperm DNA, and 35% formamide at 42° C. The carrier material is finally washed three times, for 15 minutes each, with 2x SSC, 0.2% SDS at 60° C.

[0037] The term "mutant" refers to a polynucleotide that encodes a variant.

[0038] The term "nucleic acid construct" refers to a nucleic acid molecule, having a single or double helix, that is isolated from a naturally occurring gene, or that has been modified to contain segments of nucleic acid in a manner not otherwise found in nature, or that is synthetic. The term nucleic acid construct is synonymous with the term "expression cassette" when the nucleic acid construct contains the control sequences required for expression of a coding sequence of the present invention.

[0039] The term "operably linked" refers to a structure in which control sequences are positioned in appropriate relation to a coding sequence of a polynucleotide so that the control sequences effect the expression of the coding sequence.

[0040] The terms "parent" or "parent α-amylase" refer to an α-amylase that has been modified to produce an enzyme variant of the invention. The parent may be a naturally occurring (wild-type) polypeptide or a variant thereof.

[0041] As used herein, the term "sequence identity" refers to the relatedness between two amino acid sequences or two nucleotide sequences described by the parameter "sequence identity."

[0042] For purposes of the present invention, sequence identity between two amino acid sequences is determined using the Needleman-Wunsch algorithm (Needleman and Wunsch, 1970, J. Mol. Biol. 48:443-453), preferably 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), version 5.0.0 or later. The parameters used may be a gap open penalty of 10, a gap extension penalty of 0.5, and the EBLOSUM62 (EMBOSS version of BLOSUM62) substitution matrix. The output of Needle labeled "longest identity" (obtained using the -nobrief option) is used as the percentage identity, calculated as follows: (equivalent residues × 100) / (length of alignment − total number of gaps in the alignment)

[0043] Alternatively, the parameters used are a gap open penalty of 10, a gap extension penalty of 0.5, and the EDNAFULL (EMBOSS version of NCBI NUC4.4) substitution matrix. The Needle-labeled "longest identity" output (obtained using the -nobrief option) is used as the percent identity, calculated as follows: (equivalent deoxyribonucleotides × 100) / (length of alignment − total number of gaps in alignment)

[0044] As used herein, the term "subsequence" refers to a polynucleotide having one or more (e.g., several) nucleotides deleted from the 5' and / or 3' end of a mature polypeptide coding sequence; wherein the subsequence encodes a fragment that has α-amylase activity.

[0045] The term "textile" refers to textiles and staple fibers and filaments suitable for conversion into or use as yarns, woven fabrics, knits, and nonwovens. The term encompasses yarns made from natural and synthetic (e.g., man-made) fibers. The term "textile material" is a general term for fibers, yarn intermediates, yarns, fabrics, and products (e.g., clothing and other products) made from fabrics.

[0046] The term "fabric care benefits," as used herein, is defined as those not directly related to catalytic soil removal or soil redeposition prevention, but are also important to enzyme detergency benefits. Examples of such fabric care benefits include preventing or reducing dye transfer from one fabric to another or to another part of the same fabric (effects also known as dye transfer prevention or backstain prevention), removing loose or cut fibers from the fabric surface to reduce pilling tendency or remove existing pills or fuzz (effects also known as antipilling), improving fabric softness, brightening fabric color, and removing particulate soils trapped within fabric fibers. Enzyme bleaching is yet another enzyme detergency benefit, in which catalytic activity is typically used to catalyze the formation of bleaching components such as hydrogen peroxide or other peroxides or other bleaching species.

[0047] The terms "variant" or "polypeptide variant" or "polypeptide" or "α-amylase variant," as used herein, when used with reference to a variant of the invention, refer to a polypeptide having α-amylase activity that contains modifications, i.e., substitutions, insertions, and / or deletions, at one or more (e.g., several) positions relative to the "parent α-amylase" of SEQ ID NO: 1 or 2. A substitution refers to the replacement of an amino acid occupying a position with a different amino acid; a deletion refers to the removal of an amino acid occupying a position; and an insertion refers to the addition of an amino acid immediately following and adjacent to the amino acid occupying a position. Variants of the invention have at least 20%, e.g., at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 100% of the α-amylase activity of the polypeptide of SEQ ID NO: 1-17.

[0048] The term "highly stringent conditions" refers to 12-24 hours of standard Southern blotting, for probes at least 100 nucleotides in length, followed by prehybridization and hybridization in 5x SSPE, 0.3% SDS, 200 micrograms / ml fragment-treated and denatured salmon sperm DNA, and 50% formamide at 42° C. The carrier material is finally washed three times, 15 minutes each time, with 2x SSC, 0.2% SDS at 70° C.

[0049] The term "very low stringency conditions" refers to 12-24 hours of standard Southern blotting, for probes at least 100 nucleotides in length, followed by prehybridization and hybridization in 5x SSPE, 0.3% SDS, 200 micrograms / ml fragment-treated and denatured salmon sperm DNA, and 25% formamide at 42° C. The carrier material is finally washed three times, for 15 minutes each time, with 2x SSC, 0.2% SDS at 45° C.

[0050] The term "washing performance" is defined herein as referring to the change in washing performance of an amylase of the invention relative to the washing performance of the parent amylase of SEQ ID NO: 1 or SEQ ID NO: 2. Improved washing performance can be measured by comparing so-called intensity values.

[0051] As used herein, the term "wild-type α-amylase" refers to an α-amylase expressed by a naturally occurring microorganism, such as a naturally occurring bacterium, yeast, or filamentous fungus.

[0052] The term "wash cycle" is defined herein in relation to dishwashing as a washing operation in which dishware are exposed to washing liquid for a specified period of time by circulating washing liquid to clean the dishes, spraying the washing liquid onto the dishes, and finally removing the excess washing liquid. A wash cycle may be repeated 1, 2, 3, 4, 5, or 6 times at the same or different temperatures. The dishes are then typically rinsed and dried. One of the wash cycles may be a soaking step, in which the dishes are left submerged in the washing liquid for a predetermined period of time.

[0053] The term "washing solution" is defined herein as a solution or mixture of water and detergent ingredients.

[0054] The term "wash time" in relation to automatic dishwashing is defined herein as the time taken for the entire washing process; that is, the combined wash and rinse cycles.

[0055] Unless otherwise indicated, the term "detergent composition" includes granular or powdered all-purpose or heavy-duty detergents, especially cleaning detergents; liquid, gel, or paste all-purpose detergents, especially so-called heavy-duty liquid (HDL) types; liquid detergents for delicate fabrics; hand dishwashing detergents or light-duty dishwashing detergents, especially high-foaming types; dishwashing detergents, including various tablet, granular, liquid, and rinse aid types for household and industrial use; liquid cleaning and disinfecting agents, including antibacterial hand washing types, cleaning bars, soap bars, mouthwashes, denture cleaners, car or carpet shampoos, and bathroom cleaners; hair shampoos and hair rinses; shower gels, foam baths; metal cleaners; and cleaning aids such as bleaching additives and "stain sticks" or pre-treatment types. The terms "detergent composition" and "detergent formulation" are used in reference to mixtures intended for use in a washing medium for cleaning soiled items. In some embodiments, the terms are used in reference to the washing of fabrics and / or clothes (e.g., "laundry detergents"). In another embodiment, the term refers to other detergents, such as those used to clean dishes, cutlery, etc. (eg, "dishwashing detergents").

[0056] The term "automatic dishwashing detergent composition" refers to a composition containing detergent ingredients intended for cleaning tableware such as plates, cups, glasses, bowls, spoons, knives, forks, kitchen utensils, cutlery such as ceramic, plastic, metal, porcelain, glass, and acrylic in a dishwasher. It is not intended that the present invention be limited to any particular detergent formulation or composition.

[0057] The term "detergent composition" is not limited to compositions containing surfactants. In addition to the enzymes described herein, it is contemplated that the detergent composition may include one or more ingredients selected from, for example, stabilizers, surfactants, hydrotropes, builders, co-builders, chelating agents, bleaching systems, bleach activators, bleach catalysts, polymers, metal care agents, glass care agents, crystal growth inhibitors, and fabric hueing agents.

[0058] The term "non-fabric detergent compositions" includes non-fabric surface detergent compositions, including, but not limited to, hard surface cleaning compositions such as dishwashing detergent compositions, mouthwash compositions, denture cleaner compositions, and personal cleansing compositions.

[0059] The term "effective amount of enzyme" refers to the amount of enzyme necessary to achieve the enzymatic activity required for a particular application, e.g., a defined detergent composition. Such an effective amount is readily ascertained by one of ordinary skill in the art and is based on a variety of factors, such as, for example, the particular enzyme used, the cleaning application, the specific composition of the detergent composition, and whether a liquid or dry (e.g., granular, bar) composition is desired. The term "effective amount" of enzyme refers to the amount of enzyme, as described above herein, that achieves a desired level of enzymatic activity, e.g., in a defined detergent composition. In one embodiment, the effective amount of protease is the same as the effective amount of α-amylase. In another embodiment, the effective amount of protease is different from the effective amount of α-amylase; e.g., the effective amount of protease may be greater than or less than the effective amount of α-amylase.

[0060] As used herein, the term "water hardness" or "hardness" or "dH" or "°dH" refers to the German scale of hardness, where one degree is defined as 10 milligrams of calcium oxide per liter of water.

[0061] The term "relevant washing conditions" is used herein to denote the conditions actually used in households in the detergent market segment, in particular washing temperature, time, washing machine, detergent concentration, detergent type and water hardness.

[0062] The term "additive" refers to any liquid, solid, or gaseous material selected for a particular type of detergent composition and product form (e.g., liquid, granular, powder, bar, paste, spray, tablet, gel, or foam composition), which material is preferably also compatible with the enzymes used in the composition. In some embodiments, granular compositions are in "compacted" form, while in other embodiments, liquid compositions are in "concentrated" form.

[0063] The term "stain removal enzyme" as used herein refers to an enzyme that aids in the removal of soil or contaminants from fabrics or hard surfaces. Stain removal enzymes act on specific substrates, for example, proteases act on proteins, amylases act on starches, lipases and cutinases act on lipids (fats and oils), pectinases act on pectins, and hemicellulases act on hemicelluloses. Soils are often deposits of complex mixtures of various components, which can lead to localized discoloration of the material itself or leave a sticky surface on the article that can attract soil dissolved in the wash liquor, thereby causing discoloration of the soiled area. When an enzyme acts on the specific substrate present in the soil, it breaks down or partially breaks down the substrate, thereby aiding in the removal of soil and soil components bound to the substrate during the washing process. For example, when a protease acts on grass soil, it can break down the protein components of the grass and release a green / brown color during the wash.

[0064] The term "reduced amount" in this context means that the amount of a component is less than the amount that would be used in a reference process under otherwise the same conditions. In preferred embodiments, the amount is reduced, e.g., by at least 5%, e.g., by at least 10%, at least 15%, at least 20%, or otherwise as described herein.

[0065] The term "low detergent concentration" system includes detergents in which less than about 800 ppm of detergent components are present in the wash water. Asian, e.g., Japanese, detergents are typically considered low detergent concentration systems.

[0066] The term "medium detergent concentration" system includes detergents in which from about 800 ppm to about 2000 ppm of detergent components are present in the wash water. North American detergents are generally considered medium detergent concentration systems.

[0067] The term "high detergent concentration" systems includes detergents in which more than about 2000 ppm of detergent components are present in the wash water. European detergents are generally considered high detergent concentration systems.

[0068] As used herein, the term "liquid laundry detergent composition" refers to a detergent composition that is in a stabilized liquid form and is used in a method of laundering fabrics. Thus, the detergent composition is formulated to be in liquid form.

[0069] As used herein, the term "powder laundry detergent composition" refers to a detergent composition in solid form, such as a granulate, non-dusting granulate, which is used in a method of laundering fabrics.

[0070] As used herein, the term "liquid dishwashing detergent composition" refers to a detergent composition that is in a stabilized liquid form and is used for dishwashing. Dishwashing may be any type of dishwashing, such as, for example, manual dishwashing and automatic dishwashing (ADW).

[0071] As used herein, the term "powder dishwashing detergent composition" refers to a detergent composition in solid form, such as a granule, powder, or compressed unit, that is used for dishwashing. Powder dishwashing detergent compositions are typically used in automatic dishwashing, but are not limited to such ADW, and may also be intended for use in any other type of dishwashing, such as manual dishwashing.

[0072] The term "delta strength" or "delta strength value" is defined herein as the result of measuring the strength of a test material, e.g., melamine tile (Center For Test materials BV, PO Box 120, 3133 KT Vlaardingen, the Netherlands) or hard surface soiled with starch DM-277. Delta strength is the strength value of the test material washed with amylase minus the strength value of the test material washed without amylase.

[0073] As used herein, the term "numbering is according to ..." refers to the system by which each of the amino acid residues of the polypeptides of the present invention is numbered; i.e., one skilled in the art will recognize that, for example, if position 202 is numbered according to SEQ ID NO: 1, the corresponding amino acid residue in the other polypeptide can be determined by alignment of SEQ ID NO: 1 with any other polypeptide. Alignment of two or more amino acid sequences is described elsewhere herein.

[0074] Conventional mutant determination For the purposes of the present invention, the polypeptide disclosed in SEQ ID NO: 1 is used to determine the corresponding amino acid residues in other α-amylases. The amino acid sequence of the other α-amylase is aligned with the polypeptide disclosed in SEQ ID NO: 1, and based on this alignment, the amino acid position number corresponding to any amino acid residue in the mature polypeptide disclosed 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, preferably version 3.0.0 or later (EMBOSS: The European Molecular Biology Open Software Suite, Rice et al., 2000, Trends Genet. 16:276-277).

[0075] The identification of corresponding amino acid residues in other α-amylases can be confirmed by alignment of multiple polypeptide sequences using "ClustalW" (Larkin et al., 2007, Bioinformatics 23:2947-2948).

[0076] Where other enzymes diverge from the polypeptide of SEQ ID NO: 1, preventing detection of relationships by traditional sequence-based comparison (Lindahl and Elofsson, 2000, J. Mol. Biol. 295:613-615), other pairwise sequence comparison algorithms can be used. The sensitivity of sequence-based searches can be increased by using search programs that utilize probabilistic representations of polypeptide families (profiles) to search databases. For example, the PSI-BLAST program generates profiles through an iterative database search process and can detect distant homologs (Atschul et al., 1997, Nucleic Acids Res. 25:3389-3402). Sensitivity can be further increased when the family or superfamily of polypeptides has one or more representations in protein structure databases. 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 prediction, structural alignment profiles, and solvation potentials) as input to neural networks that predict the fold structure of a query sequence. Similarly, the method by 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 then be used to generate homology models for the polypeptide, and such models can be accurately evaluated using a variety of tools developed for that purpose.

[0077] For proteins of known structure, numerous tools and resources are available for searching and generating structural alignments. For example, the SCOP superfamily of proteins has been structurally aligned, and these alignments can be accessed and downloaded. Two or more protein structures can be aligned using a variety of algorithms, such as distance alignment matrices (Holm and Sander, 1998, Proteins 33:88-96) or combinatorial extension methods (Shindyalov and Bourne, 1998, Protein Engineering 11:739-747), which can be run incrementally against a query structure database along with the target structure to discover potential structural homologs (e.g., Holm and Park, 2000, Bioinformatics 16:566-567).

[0078] In describing the variants of the present invention, the following nomenclature is adopted for ease of reference: The accepted IUPAC one-letter or three-letter amino acid abbreviations are utilized.

[0079] Substitutions. The following nomenclature is used for amino acid substitutions: original amino acid, position, substituted amino acid. Thus, a substitution of threonine with alanine at position 226 is designated "Thr226Ala" or "T226A." Multiple mutations are separated by a plus sign ("+"), e.g., "Gly205Arg+Ser411Phe" or "G205R+S411F," representing substitutions of glycine (G) with arginine (R) and serine (S) with phenylalanine (F) at positions 205 and 411, respectively.

[0080] Deletions. The following nomenclature is used for amino acid deletions: original amino acid, position * Therefore, the deletion of glycine at position 195 is "Gly195 * " or "G195 *Multiple deletions are separated by a plus sign ("+"), e.g., "Gly195 * +Ser411 * " or "G195 * +S411 * "It is said that

[0081] Insertions. The following nomenclature is used for amino acid insertions: original amino acid, position, original amino acid, inserted amino acid. Thus, an insertion of lysine after glycine at position 195 is designated as "Gly195GlyLys" or "G195GK." An insertion of multiple amino acids is designated as [original amino acid, position, original amino acid, inserted amino acid #1, inserted amino acid #2; etc.]. For example, an insertion of lysine and alanine after glycine at position 195 is designated as "Gly195GlyLysAla" or "G195GKA."

[0082] In such cases, the inserted amino acid residue is numbered by adding a subscript to the amino acid residue preceding the inserted amino acid residue. Thus, in the above example, the sequence would be:

[0083] [Table 1]

[0084] Multiple Modifications. Variants containing multiple modifications are separated by a plus sign ("+"), e.g., "Arg170Tyr+Gly195Glu" or "R170Y+G195E" represent substitutions of arginine and glycine with tyrosine and glutamic acid at positions 170 and 195, respectively.

[0085] Different Modifications. When different modifications can be introduced at one position, the different alterations are separated by a comma, for example, "Arg170Tyr,Glu" denotes the substitution of arginine with tyrosine or glutamic acid at position 170. Thus, "Tyr167Gly,Ala+Arg170Gly,Ala" denotes the following variant: "Tyr167Gly+Arg170Gly", "Tyr167Gly+Arg170Ala", "Tyr167Ala+Arg170Gly", and "Tyr167Ala+Arg170Ala". [Mode for Carrying Out the Invention]

[0086] The present invention relates to the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 167, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227, 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299, 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 34 5, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476 and 481, wherein each modification is independently a substitution, insertion or deletion, and wherein the variant has a nucleotide sequence that is at least 59%, e.g., at least 10%, relative to the polypeptide of SEQ ID NOs: 1-17. , having at least 60%, such as at least 65%, such as at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity with the parent polypeptide, wherein the variant has α-amylase activity, and the variant has improved cleaning performance compared to the parent polypeptide.

[0087] In one aspect, the present invention relates to α-amylase variants of a parent α-amylase polypeptide having α-amylase activity. Thus, in a particular aspect, the present invention relates to variants of a parent α-amylase polypeptide having α-amylase activity, wherein the variants have improved cleaning performance and the variants have α-amylase activity.

[0088] In one aspect, the present invention provides a method for the detection of nucleotides containing nucleotides of interest comprising the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 167, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227, 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 27 5, 276, 284, 286, 291, 293, 295, 298, 299, 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 3 α-amylase variants of a parent α-amylase comprising a modification at one or more (e.g. several) positions corresponding to 75, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476 and 481, wherein each modification is independently a substitution, insertion or deletion, and wherein the variant has a nucleotide sequence that is at least 59%, such as at least 60%, for example at least 65%, for example at least 70%, for example at least 75%, for example at least 75%, for example at least 75%, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476 and 481, relative to the polypeptide of SEQ ID NOs: 1-17. , at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% but less than 100% sequence identity to the parent polypeptide, wherein the variant has α-amylase activity, the variant has improved cleaning performance compared to the parent polypeptide, and the parent α-amylase has the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

[0089] In one aspect, the number of modifications is 1 to 50, e.g., 1 to 45, 1 to 40, 1 to 35, 1 to 30, 1 to 25, 1 to 20, 1 to 15, 1 to 10 or 1 to 5, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 modifications.

[0090] In one aspect, the number of substitutions is 1 to 50, e.g., 1 to 45, 1 to 40, 1 to 35, 1 to 30, 1 to 25, 1 to 20, 1 to 15, 1 to 10 or 1 to 5, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 substitutions.

[0091] In one aspect, the substituted amino acid residue is different from the amino acid residue naturally occurring at that position, hi 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 amino acid residue naturally occurring at that position.

[0092] In certain embodiments, the variants may comprise pairwise deletions within particular loops of α-amylases, which have been shown to further stabilize α-amylases. Thus, in one embodiment, the variants further comprise pairwise deletions of amino acid residues corresponding to R181, G182, D183, and G184, using SEQ ID NO: 1 for numbering, where the amino acids at the positions corresponding to R181 and / or G184 are substituted, the pairwise deletions are at the positions corresponding to G182 and D183, using SEQ ID NO: 1 for numbering.

[0093] As used herein, the term "pairwise deletion" refers to the deletion of one amino acid at two separate positions. These positions may be adjacent to one another, but are not limited to adjacent pairs. Thus, a pairwise deletion may be the deletion of one amino acid and another amino acid, which may be up to three amino acids further downstream or upstream from the first deletion. Thus, in one embodiment, the variant comprises a pairwise deletion of amino acid residues selected from the group consisting of R181+G182, R181+D183, R181+G184, G182+D183, G182+G182, and D183+G184, using SEQ ID NO: 1 for numbering.

[0094] In one aspect, SEQ ID NO:2 is an amino acid sequence comprising a double deletion of amino acid residues selected from the group consisting of: R181+G182, R181+D183, R181+G184, G182+D183, G182+G182, and D183+G184, preferably D183+G184, using SEQ ID NO:1 for numbering.

[0095] In one aspect, the number of deletions is 1 to 50, e.g., 1 to 45, 1 to 40, 1 to 35, 1 to 30, 1 to 25, 1 to 20, 1 to 15, 1 to 10 or 1 to 5, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 deletions.

[0096] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227, 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299, 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0097] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0098] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0099] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0100] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0101] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0102] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0103] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0104] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0105] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 67, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T227 , 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299 , 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481, and the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0106] In another embodiment, the variants are located at the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 142, 144, 149, 158, 160, 163, 167, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204, 206, 209, 210, 212, T22 7, 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 2 99, 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476 and 481, , wherein the variant has α-amylase activity, wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 1-17.

[0107] In another aspect, useful variants described herein include the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: 1, 2, 7, 9, 11, 16, 19, 25, 37, 43, 48, 54, 56, 58, 59, 60, 63, 81, 84, 86, 90, 98, 104, 109, 111, 113, 116, 118, 125, 127, 130, 132, 133, 134, 135, 136, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312 2, 144, 149, 158, 160, 163, 167, 169, 170, 171, 172, 173, 174, 175, 176, 178, 181, 182, 186, 187, 195, 202, 203, 204 , 206, 209, 210, 212, T227, 235, 238, 246, 256, 259, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 284, 286, 291, 293, 295, 298, 299, 302, 303, 304, 306, 310, 311, 314, 315, 317, 319, 320, 323, 328, 337, 339, 345, 357, 365, 377, 375, 385, 391, 395, 400, 406, 408, 410, 431, 435, 439, 444, 445, 458, 465, 466, 469, 473, 476, and 481. , wherein the variant has α-amylase activity, and wherein the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to the polypeptides of SEQ ID NOs: 1-17.

[0108] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1, H2, G7, I9, Q11, N16, N19, N25, A37, W43, W48, N54, V56, Y58, G59, A60, L63, T81, E84, E86, R90, Q98, V104, G109, A111, F113, R116, Q118, Q125, R127, E130, S132, G133, T134, Y135, Q136, A139, G142, N144, G149, R158, Y160, D163, W167, Q169, S170, R171, Q172, L173, A174, N175, R176, Y178, R181, G182, A186, W187, N195, M202, Y2 03, A204, V206, D209, H210, E212, T227, L235, V238, M246, Q256, K259, V264, A265, E266, Y267, K269, N270, L272, G273, A274, L275, E276, W284, M286, V291, L293, Y295, Y298, Q299, N302, S303, S304, N306, R310, N311, N314, G315, L317, Q319, R320, S323, F328, G3 37, A339, Q345, D357, Q365, P377, D375, Q385, K391, Q395, R400, D406, W408, V410, S431, G435, W439, R444, Q445, R458, N465, Q466 , W469, F473, G476 and V481, wherein the variants have at least 59%, such as at least 60%, for example at least 65%, for example at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to the polypeptides of SEQ ID NOs: 1-17.

[0109] In another embodiment, the variant comprises or consists of a deletion at the position corresponding to position 1. In another embodiment, the amino acid at the position corresponding to position 1 has been deleted from the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion H1* in the polypeptide of SEQ ID NO: 2.

[0110] In another embodiment, the variant comprises or consists of a deletion at the position corresponding to position 2. In another embodiment, the amino acid at the position corresponding to position 2 has been deleted from the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion H2* in the polypeptide of SEQ ID NO: 2.

[0111] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 7. In another embodiment, the amino acid at the position corresponding to position 7 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 embodiment, the variant comprises or consists of the substitution G7A in the polypeptide of SEQ ID NO:2.

[0112] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 9. In another embodiment, the amino acid at the position corresponding to position 9 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 embodiment, the variant comprises or consists of the substitution I9M in the polypeptide of SEQ ID NO:2.

[0113] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 11. In another embodiment, the amino acid at the position corresponding to position 11 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 embodiment, the variant comprises or consists of the substitution Q11H in the polypeptide of SEQ ID NO:2.

[0114] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 16. In another embodiment, the amino acid at the position corresponding to position 16 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 embodiment, the variant comprises or consists of the substitution N16E or N16H or N16Y in the polypeptide of SEQ ID NO:2.

[0115] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 19. In another embodiment, the amino acid at the position corresponding to position 19 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 embodiment, the variant comprises or consists of the substitution N19D in the polypeptide of SEQ ID NO:2.

[0116] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 25. In another embodiment, the amino acid at the position corresponding to position 25 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 embodiment, the variant comprises or consists of the substitution N25K or N25M or N25T in the polypeptide of SEQ ID NO:2.

[0117] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 37. In another embodiment, the amino acid at the position corresponding to position 37 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 embodiment, the variant comprises or consists of the substitution A37V in the polypeptide of SEQ ID NO:2.

[0118] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 43. In another embodiment, the amino acid at the position corresponding to position 43 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 embodiment, the variant comprises or consists of the substitution W43Y in the polypeptide of SEQ ID NO:2.

[0119] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 48. In another embodiment, the amino acid at the position corresponding to position 48 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 embodiment, the variant comprises or consists of the substitution W48Y in the polypeptide of SEQ ID NO:2.

[0120] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 54. In another embodiment, the amino acid at the position corresponding to position 54 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 embodiment, the variant comprises or consists of the substitution N54Q or N54S in the polypeptide of SEQ ID NO:2.

[0121] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 56. In another embodiment, the amino acid at the position corresponding to position 56 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 embodiment, the variant comprises or consists of the substitution V56I or V56T in the polypeptide of SEQ ID NO:2.

[0122] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 58. In another embodiment, the amino acid at the position corresponding to position 58 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Val. In another embodiment, the variant comprises or consists of the substitution Y58F in the polypeptide of SEQ ID NO:2.

[0123] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 59. In another embodiment, the amino acid at the position corresponding to position 59 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 embodiment, the variant comprises or consists of the substitution G59A in the polypeptide of SEQ ID NO:2.

[0124] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 60. In another embodiment, the amino acid at the position corresponding to position 60 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution A60S or A60T in the polypeptide of SEQ ID NO:2.

[0125] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 63. In another embodiment, the amino acid at the position corresponding to position 63 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution L63F in the polypeptide of SEQ ID NO:2.

[0126] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 81. In another embodiment, the amino acid at the position corresponding to position 81 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 embodiment, the variant comprises or consists of the substitution T81A in the polypeptide of SEQ ID NO:2.

[0127] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 84. In another embodiment, the amino acid at the position corresponding to position 84 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution E84Q in the polypeptide of SEQ ID NO:2.

[0128] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 86. In another embodiment, the amino acid at the position corresponding to position 86 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution E86L in the polypeptide of SEQ ID NO:2.

[0129] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 90. In another embodiment, the amino acid at the position corresponding to position 90 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R90H or R90N or R90Q of the polypeptide of SEQ ID NO:2.

[0130] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 98. In another embodiment, the amino acid at the position corresponding to position 98 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q98N in the polypeptide of SEQ ID NO:2.

[0131] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 104. In another embodiment, the amino acid at the position corresponding to 104 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 embodiment, the variant comprises or consists of the substitution V104A in the polypeptide of SEQ ID NO:2.

[0132] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to 109. In another embodiment, the amino acid at the position corresponding to 109 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 embodiment, the variant comprises or consists of the substitution G109A in the polypeptide of SEQ ID NO:2.

[0133] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 111. In another embodiment, the amino acid at the position corresponding to position 111 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 embodiment, the variant comprises or consists of the substitution A111T in the polypeptide of SEQ ID NO:2.

[0134] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 113. In another embodiment, the amino acid at the position corresponding to position 113 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution F113A or F113G or F113N or F113Q or F113T or F113Y of the polypeptide of SEQ ID NO:2.

[0135] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 116. In another embodiment, the amino acid at the position corresponding to position 116 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R116C or R116D or R116F or R116H or R116K or R116N or R116S or R116Y of the polypeptide of SEQ ID NO:2.

[0136] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 118. In another embodiment, the amino acid at the position corresponding to 118 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q118N or Q118T in the polypeptide of SEQ ID NO:2.

[0137] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to 125. In another embodiment, the amino acid at the position corresponding to 125 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q125G or Q125S in the polypeptide of SEQ ID NO:2.

[0138] In another embodiment, the variant comprises or consists of a substitution at the position corresponding to position 127. In another embodiment, the amino acid at the position corresponding to position 127 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R127A or R127F or R127H or R127L or R127N or R127T of the polypeptide of SEQ ID NO:2.

[0139] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 130. In another embodiment, the amino acid at the position corresponding to position 130 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, GIy, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution E130D or E130F or E130I or E130K or E130L or E130N or E130S or E130T or E130V in the polypeptide of SEQ ID NO:2.

[0140] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 132. In another embodiment, the amino acid at the position corresponding to position 132 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution S132A or S132D or S132F or S132L or S132M or S132P or S132T of the polypeptide of SEQ ID NO:2.

[0141] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 133. In another embodiment, the amino acid at the position corresponding to 133 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 embodiment, the variant comprises or consists of the substitution G133D in the polypeptide of SEQ ID NO:2.

[0142] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 134. In another embodiment, the amino acid at the position corresponding to position 134 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitutions T134C or T134E or T134N or T134P or T134R or T134S or T134W or T134Y or T134A of the polypeptide of SEQ ID NO:2.

[0143] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 135. In another embodiment, the amino acid at the position corresponding to 135 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 embodiment, the variant comprises or consists of the substitution Y135H in the polypeptide of SEQ ID NO:2.

[0144] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 136. In another embodiment, the amino acid at the position corresponding to position 136 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q136D or Q136E or Q136G or 136N or Q136R or Q136S of the polypeptide of SEQ ID NO:2.

[0145] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 139. In another embodiment, the amino acid at the position corresponding to 139 is substituted with Arg, Asn, Asp, Cys, Glu, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution A139T in the polypeptide of SEQ ID NO:2.

[0146] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 142. In another embodiment, the amino acid at the position corresponding to 142 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 embodiment, the variant comprises or consists of the substitution G142H in the polypeptide of SEQ ID NO:2.

[0147] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 144. In another embodiment, the amino acid at the position corresponding to 144 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 embodiment, the variant comprises or consists of the substitution N144H in the polypeptide of SEQ ID NO:2.

[0148] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 149. In another embodiment, the amino acid at the position corresponding to 149 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 embodiment, the variant comprises or consists of the substitution G149A in the polypeptide of SEQ ID NO:2.

[0149] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 158. In another embodiment, the amino acid at the position corresponding to position 158 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R158C or R158H or R158K or R158Q or R158S of the polypeptide of SEQ ID NO:2.

[0150] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 160. In another embodiment, the amino acid at the position corresponding to position 160 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Val. In another embodiment, the variant comprises or consists of the substitution Y160D or Y160F or Y160H or Y160N in the polypeptide of SEQ ID NO:2.

[0151] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 163. In another embodiment, the amino acid at the position corresponding to 163 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 embodiment, the variant comprises or consists of the substitution D163H in the polypeptide of SEQ ID NO:2.

[0152] In another embodiment, the variant comprises or consists of a deletion at the position corresponding to position 167. In another embodiment, the variant comprises or consists of the deletion W167* in the polypeptide of SEQ ID NO:2.

[0153] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 169. In another embodiment, the amino acid at the position corresponding to position 169 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the deletion Q169* in the polypeptide of SEQ ID NO:2.

[0154] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 170. In another embodiment, the amino acid at the position corresponding to position 170 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution S170A in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion S170* in the polypeptide of SEQ ID NO: 2.

[0155] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 171. In another embodiment, the amino acid at the position corresponding to position 171 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R171H or R171K or R171L or R171Y in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion R171* in the polypeptide of SEQ ID NO: 2.

[0156] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 172. In another embodiment, the amino acid at the position corresponding to position 172 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q172K or Q172N or Q172S in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion Q172* in the polypeptide of SEQ ID NO: 2.

[0157] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 173. In another embodiment, the amino acid at the position corresponding to position 173 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution L173K in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion L173* in the polypeptide of SEQ ID NO: 2.

[0158] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 174. In another embodiment, the amino acid at the position corresponding to position 174 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution A174N or A174S in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion A174* in the polypeptide of SEQ ID NO: 2.

[0159] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 175. In another embodiment, the amino acid at the position corresponding to position 175 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 embodiment, the variant comprises or consists of the substitution N175S in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion N175* in the polypeptide of SEQ ID NO: 2.

[0160] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 176. In another embodiment, the amino acid at the position corresponding to position 176 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R176A in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion R176* in the polypeptide of SEQ ID NO: 2.

[0161] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 178. In another embodiment, the amino acid at the position corresponding to 178 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Val. In another embodiment, the variant comprises or consists of the substitution Y178F in the polypeptide of SEQ ID NO:2.

[0162] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 181. In another embodiment, the amino acid at the position corresponding to position 181 is substituted with Ala, Asp, Cys, Gln, Glu, GIy, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitutions R181A or R181C or R181E or R181G or R181H or R181K or R181N or R181Q in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion R181* in the polypeptide of SEQ ID NO: 2.

[0163] In another embodiment, the variant comprises or consists of a deletion or substitution at the position corresponding to position 182. In another embodiment, the amino acid at the position corresponding to position 182 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution G182T N175S in the polypeptide of SEQ ID NO: 2. In another embodiment, the variant comprises or consists of the deletion G182* in the polypeptide of SEQ ID NO: 2.

[0164] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 186. In another embodiment, the amino acid at the position corresponding to position 186 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution A186D or A186E or A186H or A186K or A186N or A186T of the polypeptide of SEQ ID NO:2.

[0165] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 187. In another embodiment, the amino acid at the position corresponding to 187 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution W187M in the polypeptide of SEQ ID NO:2.

[0166] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 195. In another embodiment, the amino acid at the position corresponding to position 195 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution N195D or N195F or N195H or N195Q or N195Y of the polypeptide of SEQ ID NO:2.

[0167] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 202. In another embodiment, the amino acid at the position corresponding to 202 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 embodiment, the variant comprises or consists of the substitution M202L in the polypeptide of SEQ ID NO:2.

[0168] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 203. In another embodiment, the amino acid at the position corresponding to 203 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 embodiment, the variant comprises or consists of the substitution Y203L in the polypeptide of SEQ ID NO:2.

[0169] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 204. In another embodiment, the amino acid at the position corresponding to 204 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 embodiment, the variant comprises or consists of the substitution A204V in the polypeptide of SEQ ID NO:2.

[0170] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 206. In another embodiment, the amino acid at the position corresponding to 206 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 embodiment, the variant comprises or consists of the substitution V206L in the polypeptide of SEQ ID NO:2.

[0171] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 209. In another embodiment, the amino acid at the position corresponding to 209 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 embodiment, the variant comprises or consists of the substitution D209N in the polypeptide of SEQ ID NO:2.

[0172] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 210. In another embodiment, the amino acid at the position corresponding to 210 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 embodiment, the variant comprises or consists of the substitution H210K or H210N in the polypeptide of SEQ ID NO:2.

[0173] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 212. In another embodiment, the amino acid at the position corresponding to 212 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution E212D in the polypeptide of SEQ ID NO:2.

[0174] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 227. In another embodiment, the amino acid at the position corresponding to 227 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 embodiment, the variant comprises or consists of the substitution T227K or T227N in the polypeptide of SEQ ID NO:2.

[0175] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 235. In another embodiment, the amino acid at the position corresponding to 235 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 embodiment, the variant comprises or consists of the substitution L235I in the polypeptide of SEQ ID NO:2.

[0176] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 238. In another embodiment, the amino acid at the position corresponding to 238 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 embodiment, the variant comprises or consists of the substitution V238A in the polypeptide of SEQ ID NO:2.

[0177] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 246. In another embodiment, the amino acid at the position corresponding to 246 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution M246I or M246L or M246T or M246V in the polypeptide of SEQ ID NO:2.

[0178] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 256. In another embodiment, the amino acid at the position corresponding to 256 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q256H or Q256N in the polypeptide of SEQ ID NO:2.

[0179] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 259. In another embodiment, the amino acid at the position corresponding to 259 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution K259G or K259H in the polypeptide of SEQ ID NO:2.

[0180] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 264. In another embodiment, the amino acid at the position corresponding to 264 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Tyr. In another embodiment, the variant comprises or consists of the substitution V264A or V246I or V264T of the polypeptide of SEQ ID NO:2.

[0181] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 265. In another embodiment, the amino acid at the position corresponding to 265 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 embodiment, the variant comprises or consists of the substitution A265G in the polypeptide of SEQ ID NO:2.

[0182] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 266. In another embodiment, the amino acid at the position corresponding to 266 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, GIy, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution E266V in the polypeptide of SEQ ID NO:2.

[0183] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 267. In another embodiment, the amino acid at the position corresponding to 267 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Val. In another embodiment, the variant comprises or consists of the substitution Y267F or Y267H or Y267L of the polypeptide of SEQ ID NO:2.

[0184] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 269. In another embodiment, the amino acid at the position corresponding to 269 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution K269M or K269Q or K269R of the polypeptide of SEQ ID NO:2.

[0185] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 270. In another embodiment, the amino acid at the position corresponding to 270 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution N270G or N270P in the polypeptide of SEQ ID NO:2.

[0186] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 272. In another embodiment, the amino acid at the position corresponding to 272 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution L272I in the polypeptide of SEQ ID NO:2.

[0187] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 273. In another embodiment, the amino acid at the position corresponding to 273 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 embodiment, the variant comprises or consists of the substitution G273V in the polypeptide of SEQ ID NO:2.

[0188] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 274. In another embodiment, the amino acid at the position corresponding to 274 is substituted with Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution A274K or A274S in the polypeptide of SEQ ID NO:2.

[0189] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 275. In another embodiment, the amino acid at the position corresponding to 275 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution L275A or L275I or L275V of the polypeptide of SEQ ID NO:2.

[0190] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 276. In another embodiment, the amino acid at the position corresponding to 276 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution E276N in the polypeptide of SEQ ID NO:2.

[0191] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 291. In another embodiment, the amino acid at the position corresponding to 291 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution V291A or V291I or V291T of the polypeptide of SEQ ID NO:2.

[0192] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 284. In another embodiment, the amino acid at the position corresponding to 284 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution W284R or W284Y in the polypeptide of SEQ ID NO:2.

[0193] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 286. In another embodiment, the amino acid at the position corresponding to 286 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution M286L in the polypeptide of SEQ ID NO:2.

[0194] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 291. In another embodiment, the amino acid at the position corresponding to 291 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Tyr. In another embodiment, the variant comprises or consists of the substitution V291A or V291I or V291T of the polypeptide of SEQ ID NO:2.

[0195] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 293. In another embodiment, the amino acid at the position corresponding to 293 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution L293I or L293V in the polypeptide of SEQ ID NO:2.

[0196] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 295. In another embodiment, the amino acid at the position corresponding to 295 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 embodiment, the variant comprises or consists of the substitution Y295F in the polypeptide of SEQ ID NO:2.

[0197] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 298. In another embodiment, the amino acid at the position corresponding to 298 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Val. In another embodiment, the variant comprises or consists of the substitution Y298E or Y298N in the polypeptide of SEQ ID NO:2.

[0198] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 299. In another embodiment, the amino acid at the position corresponding to 299 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q299N or Q299Y in the polypeptide of SEQ ID NO:2.

[0199] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 302. In another embodiment, the amino acid at the position corresponding to 302 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution N302A or N302H or N302K or N302Q of the polypeptide of SEQ ID NO:2.

[0200] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 303. In another embodiment, the amino acid at the position corresponding to 303 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 embodiment, the variant comprises or consists of the substitution S303G in the polypeptide of SEQ ID NO:2.

[0201] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 304. In another embodiment, the amino acid at the position corresponding to 304 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution S304G or S304Q of the polypeptide of SEQ ID NO:2.

[0202] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 306. In another embodiment, the amino acid at the position corresponding to 306 is substituted with Ala, Arg, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution N306H or N306K or N306Q or N306R or N306Y of the polypeptide of SEQ ID NO:2.

[0203] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 310. In another embodiment, the amino acid at the position corresponding to 310 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R310N or R310S or R310Q of the polypeptide of SEQ ID NO:2.

[0204] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 311. In another embodiment, the amino acid at the position corresponding to 311 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 embodiment, the variant comprises or consists of the substitution N311K or N311R in the polypeptide of SEQ ID NO:2.

[0205] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 314. In another embodiment, the amino acid at the position corresponding to 314 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 embodiment, the variant comprises or consists of the substitution N314Q in the polypeptide of SEQ ID NO:2.

[0206] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 315. In another embodiment, the amino acid at the position corresponding to 315 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 embodiment, the variant comprises or consists of the substitution G315N in the polypeptide of SEQ ID NO:2.

[0207] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 317. In another embodiment, the amino acid at the position corresponding to 317 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution L317V in the polypeptide of SEQ ID NO:2.

[0208] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 319. In another embodiment, the amino acid at the position corresponding to 319 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q319H in the polypeptide of SEQ ID NO:2.

[0209] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 320. In another embodiment, the amino acid at the position corresponding to 320 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R320K or R320Q or R320S of the polypeptide of SEQ ID NO:2.

[0210] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 323. In another embodiment, the amino acid at the position corresponding to 323 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 embodiment, the variant comprises or consists of the substitution S323T or S323K in the polypeptide of SEQ ID NO:2.

[0211] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 328. In another embodiment, the amino acid at the position corresponding to 328 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution F328L in the polypeptide of SEQ ID NO:2.

[0212] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 337. In another embodiment, the amino acid at the position corresponding to 337 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 embodiment, the variant comprises or consists of the substitution G337D or G337E in the polypeptide of SEQ ID NO:2.

[0213] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 339. In another embodiment, the amino acid at the position corresponding to 339 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 embodiment, the variant comprises or consists of the substitution A339S in the polypeptide of SEQ ID NO:2.

[0214] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 345. In another embodiment, the amino acid at the position corresponding to 345 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q345N or Q345R of the polypeptide of SEQ ID NO:2.

[0215] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 357. In another embodiment, the amino acid at the position corresponding to 357 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution L357F in the polypeptide of SEQ ID NO:2.

[0216] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 365. In another embodiment, the amino acid at the position corresponding to 365 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q365A or Q365C or Q365E or Q365H or Q365K or Q365M or Q365S of the polypeptide of SEQ ID NO:2.

[0217] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 377. In another embodiment, the amino acid at the position corresponding to 377 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution P377K or P377T in the polypeptide of SEQ ID NO:2.

[0218] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 375. In another embodiment, the amino acid at the position corresponding to 375 is substituted with Ala, Arg, Asn, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution D375H or D375N or D375Y in the polypeptide of SEQ ID NO:2.

[0219] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 386. In another embodiment, the amino acid at the position corresponding to 386 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q386L in the polypeptide of SEQ ID NO:2.

[0220] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 391. In another embodiment, the amino acid at the position corresponding to 391 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution K391A in the polypeptide of SEQ ID NO:2.

[0221] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 395. In another embodiment, the amino acid at the position corresponding to 395 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q395K in the polypeptide of SEQ ID NO:2.

[0222] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 400. In another embodiment, the amino acid at the position corresponding to 400 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 embodiment, the variant comprises or consists of the substitution R400S in the polypeptide of SEQ ID NO:2.

[0223] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 406. In another embodiment, the amino acid at the position corresponding to 406 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 embodiment, the variant comprises or consists of the substitution D406H in the polypeptide of SEQ ID NO:2.

[0224] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 408. In another embodiment, the amino acid at the position corresponding to 408 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 embodiment, the variant comprises or consists of the substitution W408H in the polypeptide of SEQ ID NO:2.

[0225] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 410. In another embodiment, the amino acid at the position corresponding to 410 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 embodiment, the variant comprises or consists of the substitution V410I in the polypeptide of SEQ ID NO:2.

[0226] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 431. In another embodiment, the amino acid at the position corresponding to 431 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 embodiment, the variant comprises or consists of the substitution S431F in the polypeptide of SEQ ID NO:2.

[0227] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 435. In another embodiment, the amino acid at the position corresponding to 435 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 embodiment, the variant comprises or consists of the substitution G435C of the polypeptide of SEQ ID NO:2.

[0228] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 439. In another embodiment, the amino acid at the position corresponding to 439 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 embodiment, the variant comprises or consists of the substitution W439R or W439T in the polypeptide of SEQ ID NO:2.

[0229] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 444. In another embodiment, the amino acid at the position corresponding to 444 is substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R444T in the polypeptide of SEQ ID NO:2.

[0230] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 445. In another embodiment, the amino acid at the position corresponding to 445 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q445S in the polypeptide of SEQ ID NO:2.

[0231] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 178. In another embodiment, the amino acid at the position corresponding to 178 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, or Val. In another embodiment, the variant comprises or consists of the substitution Y178F in the polypeptide of SEQ ID NO:2.

[0232] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 458. In another embodiment, the amino acid at the position corresponding to 458 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution R458K in the polypeptide of SEQ ID NO:2.

[0233] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 465. In another embodiment, the amino acid at the position corresponding to 465 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution N465G in the polypeptide of SEQ ID NO:2.

[0234] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 466. In another embodiment, the amino acid at the position corresponding to 466 is substituted with Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Q466S in the polypeptide of SEQ ID NO:2.

[0235] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 469. In another embodiment, the amino acid at the position corresponding to 469 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 embodiment, the variant comprises or consists of the substitution W469N or W469Y in the polypeptide of SEQ ID NO:2.

[0236] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to position 178. In another embodiment, the amino acid at the position corresponding to position 178 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution Y178F in the polypeptide of SEQ ID NO:2.

[0237] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 473. In another embodiment, the amino acid at the position corresponding to 473 is substituted with Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, He, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val. In another embodiment, the variant comprises or consists of the substitution F473I or F473P or F473S in the polypeptide of SEQ ID NO:2.

[0238] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 476. In another embodiment, the amino acid at the position corresponding to 476 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 embodiment, the variant comprises or consists of the substitution G476K in the polypeptide of SEQ ID NO:2.

[0239] In another embodiment, the variant comprises or consists of a substitution at a position corresponding to 481. In another embodiment, the amino acid at the position corresponding to 481 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 embodiment, the variant comprises or consists of the substitution V481A in the polypeptide of SEQ ID NO:2.

[0240] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K269M ;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I;V291 T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N306Q;N30 6R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328L;G337D;G33 7E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N;D375Y;Q386L;K3 91A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W469N;W469Y;F473I;F4 73P; F473S; G476K; and V481A, wherein the variants have at least 59%, such as at least 60%, such as at least 65%, such as at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to the polypeptides of SEQ ID NOs: 1-17;

[0241] The variants have at least 20%, e.g., at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 100% of the α-amylase activity of the polypeptides of SEQ ID NOs: 1-17.

[0242] In one embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, 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 a parent polypeptide having α-amylase activity.

[0243] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:1.

[0244] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:2.

[0245] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:3.

[0246] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:4.

[0247] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:5.

[0248] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:6.

[0249] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:7.

[0250] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:8.

[0251] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO:9.

[0252] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO: 10.

[0253] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO: 11.

[0254] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO: 12.

[0255] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO: 13.

[0256] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO: 14.

[0257] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO: 15.

[0258] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO: 16.

[0259] In another embodiment, the variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, such as at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to SEQ ID NO: 17.

[0260] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 69N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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;

[0261] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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:2;

[0262] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 69N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 3;

[0263] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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:4;

[0264] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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:5;

[0265] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 6;

[0266] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 69N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 7;

[0267] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 8;

[0268] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291 I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K; N306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F32 8L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N ;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W4 69N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 9;

[0269] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I ;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N 306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328 L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N; D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W46 9N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 10;

[0270] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I ;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N 306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328 L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N; D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W46 9N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 11;

[0271] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I ;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N 306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328 L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N; D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W46 9N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 12;

[0272] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I ;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N 306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328 L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N; D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W46 9N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 13;

[0273] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I ;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N 306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328 L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N; D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W46 9N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 14;

[0274] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I ;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N 306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328 L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N; D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W46 9N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 15;

[0275] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I ;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N 306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328 L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N; D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W46 9N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 16;

[0276] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y;R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q1 18T;Q125G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F ;E130I;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S 132L;S132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134 S;T134W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S; A139T;G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y16 0F;T160H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171* ;R171H;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A1 74*;A174N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181 C;R181E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A 186H;A186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M20 2L;Y203L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F;Y267H;Y267L;K2 69M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275V;E276N;W284R;W284Y;M286L;V291A;V291I ;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q299Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N 306Q;N306R;N306Y;R310N;R310S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328 L;G337D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P377T;D375H;D375N; D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W46 9N; W469Y; F473I; F473P; F473S; G476K; and V481A, wherein the variants have at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, 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: 17;

[0277] In one aspect, the modifications at one or more positions are selected from the following, using SEQ ID NO: 1 for numbering: H1*; H2*, G7A; I9M; Q11H; N16E; N16H; N16Y; N19D; N25K; N25M; N25T; A37V; W43Y; W48Y; N54Q; N54S; V56I; V56T; Y58F; G59A; A60S; A60T; L63F; T81A; E84Q; E86L; R90H; R90N; R90Q; Q98N; V104A; G109A; A111T; F113A; F113G; F113N; F113Q; F113T; F113Y; R116C;R116D;R116F;R116H;R116K;R116N;R116S;R116Y;Q118N;Q118T;Q1 25G;Q125S;R127A;R127F;R127H;R127L;R127N;R127T;E130D;E130F;E130I ;E130K;E130L;E130N;E130S;E130T;E130V;S132A;S132D;S132F;S132L;S 132M;S132P;S132T;G133D;T134C;T134E;T134N;T134P;T134R;T134S;T134 W;T134Y;T134A;Y135H;Q136D;Q136E;Q136G;Q136N;Q136R;Q136S;A139T; G142H;N144H;G149A;R158C;R158H;R158K;R158Q;R158S;Y160D;Y160F;T16 0H;Y160N;D163H;W167*;Q169*;Q169E;Q169F;S170*;S170A;R171*;R171H ;R171K;R171L;R171Y;Q172*;Q172K;Q172N;Q172S;L173*;L173K;A174*;A1 74N;A174S;N175*;N175S;R176*;R176A;Y178F;R181*;R181A;R181C;R181 E;R181G;R181H;R181K;R181N;R181Q;G182*;G182T;A186D;A186E;A186H;A 186K;A186N;A186T;W187M;N195D;N195F;N195H;N195Q;N195Y;M202L;Y20 3L;A204V;V206L;D209N;H210K;H210N;E212D;T227K;T227N;L235I;V238A;M246I;M246L;M246T;M246V;Q256H;Q256N;K259G;K259H;V264A;V246I;V264T;A265G;E266V;Y267F ;Y267H;Y267L;K269M;K269Q;K269R;N270G;N270P;L272I;G273V;A274K;A274S;L275A;L275I;L275 V;E276N;W284R;W284Y;M286L;V291A;V291I;V291T;L293I;L293V;Y295F;Y298E;Y298N;Q299N;Q29 9Y;N302A;N302H;N302K;N302Q;S303G;S304G;S304Q;N306H;N306K;N306Q;N306R;N306Y;R310N;R31 0S;R310Q;N311K;N311R;N314Q;G315N;L317V;Q319H;R320K;R320Q;R320S;S323T;H323K;F328L;G3 37D;G337E;A339S;Q345N;Q345R;L357F;Q365A;Q365C;Q365E;Q365H;Q365K;Q365M;Q365S;P377K;P3 Corresponding to 77T;D375H;D375N;D375Y;Q386L;K391A;Q395K;R400S;D406H;W408H;V410I;S431F;G435C;W439R;W439T;R444T;Q445S;R458K;N465G;Q466S;W469N;W469Y;F473I;F473P;F473S;G476K; and V481A.

[0278] In one aspect, the variants have the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: A174*+A339S, A174*+G109A, A174*+G149A, A174*+G182T, A174*+H1*, A174*+I9M, A174*+K391A, A174*+M202L, A174*+N16Y, A174*+N195F, A174*+N54S, A174*+Q169E, A174*+Q169E, A174*+Q172K, A174*+Q299Y, A174*+Q345R, A174*+Q365S, A174*+Q36 ...S, A174*+ 174*+R320K, A174*+R458K, A174*+S323T, A174*+V206L, A174*+Y295F, A33 9S+G109A, A339S+G149A, A339S+G182T, A339S+H1*, A339S+I9M, A339S+K391 A, A339S+M202L, A339S+N16Y, A339S+N195F, A339S+N54S, A339S+Q169E, A3 39S+Q169E, A339S+Q172K, A339S+Q299Y, A339S+Q345R, A339S+Q365S, A339S +R320K, A339S+R458K, A339S+S323T, A339S+V206L, A339S+Y295F, G109A+G 149A, G109A+G182T, G109A+H1*, G109A+I9M, G109A+K391A, G109A+M202L, G 109A+N16Y, G109A+N195F, G109A+N54S, G109A+Q169E, G109A+Q169E, G109A +Q172K, G109A+Q299Y, G109A+Q345R, G109A+Q365S, G109A+R320K, G109A+R4 58K, G109A+S323T, G109A+V206L, G109A+Y295F, G149A+G182T, G149A+H1*, G149A+I9M, G149A+K391A, G149A+M202L, G149A+N16Y, G149A+N195F, G149A+ N54S, G149A+Q169E, G149A+Q169E, G149A+Q172K, G149A+Q299Y, G149A+Q34 5R, G149A+Q365S, G149A+R320K, G149A+R458K, G149A+S323T, G149A+V206L,<h2 style=";text-align:left;direction:ltr">G149A+Y295F、G182T+H1*、G182T+I9M、G182T+K391A、G182T+M202L、G182T+ N16Y、G182T+N195F、G182T+N54S、G182T+Q169E、G182T+Q169E、G182T+Q172 K、G182T+Q299Y、G182T+Q345R、G182T+Q365S、G182T+R320K、G182T+R458K、 G182T+S323T、G182T+V206L、G182T+Y295F、H1*+I9M、H1*+K391A、H1*+M202L H1*+N16Y, H1*+N195F, H1*+N54S, H1*+Q169E, H1*+Q169E, H1*+Q172K, H1*+Q299Y, H1*+Q345R, H1*+Q365S, H1*+R320K, H1*+R458K, H1*+S323T, H1*+V2 06L, H1*+Y295F, I9M+K391A, I9M+M202L, I9M+N16Y, I9M+N195F, I9M+N54S, I9M+Q169E, I9M+Q169E, I9M+Q172K, I9M+Q299Y, I9M+Q345R, I9M+Q365S, I9M +R320K, I9M+R458K, I9M+S323T, I9M+V206L, I9M+Y295F, K391A+M202L, K391A+N16Y, K391A+N195F, K391A+N54S, K391A+Q169E, K391A+Q169E, K391A+Q1 72K, K391A+Q299Y, K391A+Q345R, K391A+Q365S, K391A+R320K, K391A+R458K, K391A+S323T, K391A+V206L, K391A+Y295F, M202L+N16Y, M202L+N195F, M2 02L+N54S, M202L+Q169E, M202L+Q169E, M202L+Q172K, M202L+Q299Y, M202L+Q345R, M202L+Q365S, M202L+R320K, M202L+R458K, M202L+S323T, M202L+V2 06L、M202L+Y295F、N16Y+N195F、N16Y+N54S、N16Y+Q169E、N16Y+Q169E、N16 Y+Q172K、N16Y+Q299Y、N16Y+Q345R、N16Y+Q365S、N16Y+R320K、N16Y+R458K、N16Y+S323T, N16Y+V206L, N16Y+Y295F, N195F+N54S, N195F+Q169E, N195F +Q169E, N195F+Q172K, N195F+Q299Y, N195F+Q345R, N195F+Q365S, N195F+ R320K, N195F+R458K, N195F+S323T, N195F+V206L, N195F+Y295F, N54S+Q1 69E, N54S+Q169E, N54S+Q172K, N54S+Q299Y, N54S+Q345R, N54S+Q365S, N5 4S+R320K, N54S+R458K, N54S+S323T, N54S+V206L, N54S+Y295F, Q169E+Q1 69E, Q169E+Q172K, Q169E+Q299Y, Q169E+Q345R, Q169E+Q365S, Q169E+R32 0K, Q169E+R458K, Q169E+S323T, Q169E+V206L, Q169E+Y295F, Q169E+Q172 K, Q169E+Q299Y, Q169E+Q345R, Q169E+Q365S, Q169E+R320K, Q169E+R458K, Q169E+S323T, Q169E+V206L, Q169E+Y295F, Q172K+Q299Y, Q172K+Q345R, Q 172K+Q365S, Q172K+R320K, Q172K+R458K, Q172K+S323T, Q172K+V206L, Q1 72K+Y295F, Q299Y+Q345R, Q299Y+Q365S, Q299Y+R320K, Q299Y+R458K, Q29 9Y+S323T, Q299Y+V206L, Q299Y+Y295F, Q345R+Q365S, Q345R+R320K, Q345 R+R458K, Q345R+S323T, Q345R+V206L, Q345R+Y295F, Q365S+R320K, Q365S+R458K, Q365S+S323T, Q365S+V206L, Q365S+Y295F, R320K+R458K, R320K+S323T, R320K+V206L, R320K+Y295F, R458K+S323T, R458K+V206L, R458K+Y295F, S323T+V206L, S323T+Y295F, V206L+Y295F, wherein said variantsIt has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to the polypeptides of SEQ ID NOs: 1 to 17.

[0279] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: A174*+A339S+G109A, A174*+A339S+G149A, A174*+A339S+G182T, A174*+A339S+H1*, A174*+A339S+I9M, A174*+A339S+K391A, A174*+A339S+M202L, A174*+A339S+N16Y, A174*+A339S+N195F, A174*+A339S+N54S, A174*+A339S+Q169E, A174*+A339S+H1* ... *+A339S+Q169E, A174*+A339S+Q172K, A174*+A339S+Q299Y, A174*+A339S +Q345R, A174*+A339S+Q365S, A174*+A339S+R320K, A174*+A339S+R458K, A 174*+A339S+S323T, A174*+A339S+V206L, A174*+A339S+Y295F, A174*+G10 9A+G149A, A174*+G109A+G182T, A174*+G109A+H1*, A174*+G109A+I9M, A17 4*+G109A+K391A, A174*+G109A+M202L, A174*+G109A+N16Y, A174*+G109A +N195F, A174*+G109A+N54S, A174*+G109A+Q169E, A174*+G109A+Q169E, A1 74*+G109A+Q172K, A174*+G109A+Q299Y, A174*+G109A+Q345R, A174*+G10 9A+Q365S, A174*+G109A+R320K, A174*+G109A+R458K, A174*+G109A+S323T , A174*+G109A+V206L, A174*+G109A+Y295F, A174*+G149A+G182T, A174*+ G149A+H1*, A174*+G149A+I9M, A174*+G149A+K391A, A174*+G149A+M202L, A174*+G149A+N16Y, A174*+G149A+N195F, A174*+G149A+N54S, A174*+G149 A+Q169E, A174*+G149A+Q169E, A174*+G149A+Q172K, A174*+G149A+Q299Y,<h2 style=";text-align:left;direction:ltr">A174*+G149A+Q345R、A174*+G149A+Q365S、A174*+G149A+R320K、A174*+G149A+R458K、A174*+G149A+S323T、A174*+G149A+V206L、A174*+G149A+Y295F 、A174*+G182T+H1*、A174*+G182T+I9M、A174*+G182T+K391A、A174*+G182T +M202L、A174*+G182T+N16Y、A174*+G182T+N195F、A174*+G182T+N54S、A174 *+G182T+Q169E、A174*+G182T+Q169E、A174*+G182T+Q172K、A174*+G182T+ Q299Y、A174*+G182T+Q345R、A174*+G182T+Q365S、A174*+G182T+R320K、A17 4*+G182T+R458K、A174*+G182T+S323T、A174*+G182T+V206L、A174*+G182T +Y295F、A174*+H1*+I9M、A174*+H1*+K391A、A174*+H1*+M202L、A174*+H1*+ N16Y、A174*+H1*+N195F、A174*+H1*+N54S、A174*+H1*+Q169E、A174*+H1*+ Q169E、A174*+H1*+Q172K、A174*+H1*+Q299Y、A174*+H1*+Q345R、A174*+H1* +Q365S、A174*+H1*+R320K、A174*+H1*+R458K、A174*+H1*+S323T、A174*+H 1*+V206L、A174*+H1*+Y295F、A174*+I9M+K391A、A174*+I9M+M202L、A174*+ I9M+N16Y, A174*+I9M+N195F, A174*+I9M+N54S, A174*+I9M+Q169E, A174*+I9M+Q169E, A174*+I9M+Q172K, A174*+I9M+Q299Y, A174*+I9M+Q345R, A174* +I9M+Q365S、A174*+I9M+R320K、A174*+I9M+R458K、A174*+I9M+S323T、A174*+I9M+V206L、A174*+I9M+Y295F、A174*+K391A+M202L、A174*+K391A+N16Y、A174*+K391A+N195F、A174*+K391A+N54S、A174*+K391A+Q169E、A174*+K391A+Q169E、A174*+K391A+Q172K、A174*+K391A+Q299Y、A174*+K391A+Q345R、A174*+K391A+Q365S、A174*+K391A+R320K、A174*+K391A+R458K、A174*+K391A+S323T、A174*+K391A+V206L、A174*+K391A+Y295F、A174*+M202L+N16Y、A174*+M202L+N195F、A174*+M202L+N54S、A174*+M202L+Q169E、A174*+M202L+Q169E、A174*+M202L+Q172K、A174*+M202L+Q299Y、A174*+M202L+Q345R、A174*+M202L+Q365S、A174*+M202L+R320K、A174*+M202L+R458K、A174*+M202L+S323T、A174*+M202L+V206L、A174*+M202L+Y295F、A174*+N16Y+N195F、A174*+N16Y+N54S、A174*+N16Y+Q169E、A174*+N16Y+Q169E、A174*+N16Y+Q172K、A174*+N16Y+Q299Y、A174*+N16Y+Q345R、A174*+N16Y+Q365S、A174*+N16Y+R320K、A174*+N16Y+R458K、A174*+N16Y+S323T、A174*+N16Y+V206L、A174*+N16Y+Y295F、A174*+N195F+N54S、A174*+N195F+Q169E、A174*+N195F+Q169E、A174*+N195F+Q172K、A174*+N195F+Q299Y、A174*+N195F+Q345R、A174*+N195F+Q365S、A174*+N195F+R320K、A174*+N195F+R458K、A174*+N195F+S323T、A174*+N195F+V206L、A174*+N195F+Y295F、A174*+N54S+Q169E、A174*+N54S+Q169E、A174*+N54S+Q172K、A174*+N54S+Q299Y、A174*+N54S+Q345R、A174*+N54S+Q365S、A174*+N54S+R320K、A174*+N54S+R458K、A174*+N54S+S323T、A174*+N54S+V206L、A174*+N54S+Y295F、A174*+Q169E+Q169E、A174*+Q169E+Q172K、A174*+Q169E+Q299Y、A174*+Q169E+Q345R、A174*+Q169E+Q365S、A174*+Q169E+R320K、A174*+Q169E+R458K、A174*+Q169E+S323T、A174*+Q169E+V206L、A174*+Q169E+Y295F、A174*+Q169E+Q172K、A174*+Q169E+Q299Y、A174*+Q169E+Q345R、A174*+Q169E+Q365S、A174*+Q169E+R320K、A174*+Q169E+R458K、A174*+Q169E+S323T、A174*+Q169E+V206L、A174*+Q169E+Y295F、A174*+Q172K+Q299Y、A174*+Q172K+Q345R、A174*+Q172K+Q365S、A174*+Q172K+R320K、A174*+Q172K+R458K、A174*+Q172K+S323T、A174*+Q172K+V206L、A174*+Q172K+Y295F、A174*+Q299Y+Q345R、A174*+Q299Y+Q365S、A174*+Q299Y+R320K、A174*+Q299Y+R458K、A174*+Q299Y+S323T、A174*+Q299Y+V206L、A174*+Q299Y+Y295F、A174*+Q345R+Q365S、A174*+Q345R+R320K、A174*+Q345R+R458K、A174*+Q345R+S323T、A174*+Q345R+V206L、A174*+Q345R+Y295F、A174*+Q365S+R320K、A174*+Q365S+R458K、A174*+Q365S+S323T、A174*+Q365S+V206L、A174*+Q365S+Y295F、A174*+R320K+R458K、A174*+R320K+S323T、A174*+R320K+V206L、A174*+R320K+Y295F、<h2 style=";text-align:left;direction:ltr">A174*+R458K+S323T, A174*+R458K+V206L, A174*+R458K+Y295F, A174*+S323T+V206L, A174*+S323T+Y295F, A174*+V206L+Y295F, A339S+G109A+G14 9A, A339S+G109A+G182T, A339S+G109A+H1*, A339S+G109A+I9M, A339S+G109A+K391A, A339S+G109A+M202L, A339S+G109A+N16Y, A339S+G109A+N195F, A339S+G109A+N54S, A339S+G109A+Q169E, A339S+G109A+Q169E, A339S+G109A+Q172K, A339S+G109A+Q299Y, A339S+G109A+Q345R, A339S+G109A+Q365S A339S+G109A+R320K, A339S+G109A+R458K, A339S+G109A+S323T, A339S+G109A+V206L, A339S+G109A+Y295F, A339S+G149A+G182T, A339S+G149A+H1* A339S+G149A+I9M, A339S+G149A+K391A, A339S+G149A+M202L, A339S+G149A+N16Y, A339S+G149A+N195F, A339S+G149A+N54S, A339S+G149A+Q169E A339S+G149A+Q169E, A339S+G149A+Q172K, A339S+G149A+Q299Y, A339S+G149A+Q345R, A339S+G149A+Q365S, A339S+G149A+R320K, A339S+G149A+R458 K, A339S+G149A+S323T, A339S+G149A+V206L, A339S+G149A+Y295F, A339S+G182T+H1*, A339S+G182T+I9M, A339S+G182T+K391A, A339S+G182T+M202L, A339S+G182T+N16Y, A339S+G182T+N195F, A339S+G182T+N54S, A339S+G182T+Q169E, A339S+G182T+Q169E, A339S+G182T+Q172K, A339S+G182T+Q299Y,<h2 style=";text-align:left;direction:ltr">A339S+G182T+Q345R, A339S+G182T+Q365S, A339S+G182T+R320K, A339S+G182T+R458K, A339S+G182T+S323T, A339S+G182T+V206L, A339S+G182T+Y295F, A339S+H1*+I9M, A339S+H1*+K391A,<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">A339S+H1*+M202L, A339S+H1*+N16Y, A339S+H1*+N195F, A339S+H1*+N54S, A339S+H1*+Q169E, A339S+H1*+Q169E, A339S+H1*+Q172K, A339S+H1*+Q299 Y, A339S+H1*+Q345R, A339S+H1*+Q365S, A339S+H1*+R320K, A339S+H1*+R458K, A339S+H1*+S323T, A339S+H1*+V206L, A339S+H1*+Y295F, A339S+I9M+ K391A, A339S+I9M+M202L, A339S+I9M+N16Y, A339S+I9M+N195F, A339S+I9M+N54S, A339S+I9M+Q169E, A339S+I9M+Q169E, A339S+I9M+Q172K, A339S+I9 M+Q299Y, A339S+I9M+Q345R, A339S+I9M+Q365S, A339S+I9M+R320K, A339S+I9M+R458K, A339S+I9M+S323T, A339S+I9M+V206L, A339S+I9M+Y295F, A339 S+K391A+M202L, A339S+K391A+N16Y, A339S+K391A+N195F, A339S+K391A+N54S, A339S+K391A+Q169E, A339S+K391A+Q169E, A339S+K391A+Q172K, A339 S+K391A+Q299Y, A339S+K391A+Q345R, A339S+K391A+Q365S, A339S+K391A+R320K, A339S+K391A+R458K, A339S+K391A+S323T, A339S+K391A+V206L, A3 39S+K391A+Y295F, A339S+M202L+N16Y, A339S+M202L+N195F, A339S+M202L+N54S, A339S+M202L+Q169E, A339S+M202L+Q169E, A339S+M202L+Q172K, A3 39S+M202L+Q299Y、A339S+M202L+Q345R、A339S+M202L+Q365S、A339S+M202L+R320K、A339S+M202L+R458K、A339S+M202L+S323T、A339S+M202L+V206L、<h2 style=";text-align:left;direction:ltr">A339S+M202L+Y295F, A339S+N16Y+N195F, A339S+N16Y+N54S, A339S+N16Y+Q169E, A339S+N16Y+Q169E, A339S+N16Y+Q172K, A339S+N16Y+Q299Y, A339S+ N16Y+Q345R, A339S+N16Y+Q365S, A339S+N16Y+R320K, A339S+N16Y+R458K, A339S+N16Y+S323T, A339S+N16Y+V206L, A339S+N16Y+Y295F, A339S+N195F+ N54S, A339S+N195F+Q169E, A339S+N195F+Q169E, A339S+N195F+Q172K, A339S+N195F+Q299Y, A339S+N195F+Q345R, A339S+N195F+Q365S, A339S+N195F+ R320K, A339S+N195F+R458K, A339S+N195F+S323T, A339S+N195F+V206L, A339S+N195F+Y295F, A339S+N54S+Q169E, A339S+N54S+Q169E, A339S+N54S+Q1 72K, A339S+N54S+Q299Y, A339S+N54S+Q345R, A339S+N54S+Q365S, A339S+N54S+R320K, A339S+N54S+R458K, A339S+N54S+S323T, A339S+N54S+V206L, A3 39S+N54S+Y295F, A339S+Q169E+Q169E, A339S+Q169E+Q172K, A339S+Q169E+Q299Y, A339S+Q169E+Q345R, A339S+Q169E+Q365S, A339S+Q169E+R320K, A3 39S+Q169E+R458K、A339S+Q169E+S323T、A339S+Q169E+V206L、A339S+Q169 E+Y295F、A339S+Q169E+Q172K、A339S+Q169E+Q299Y、A339S+Q169E+Q345R、A 339S+Q169E+Q365S, A339S+Q169E+R320K, A339S+Q169E+R458K, A339S+Q169E+S323T, A339S+Q169E+V206L, A339S+Q169E+Y295F, A339S+Q172K+Q299Y,<h2 style=";text-align:left;direction:ltr">A339S+Q172K+Q345R, A339S+Q172K+Q365S, A339S+Q172K+R320K, A339S+Q172K+R458K, A339S+Q172K+S323T, A339S+Q172K+V206L, A339S+Q172K+Y295 F、A339S+Q299Y+Q345R、A339S+Q299Y+Q365S、A339S+Q299Y+R320K、A339S+ Q299Y+R458K、A339S+Q299Y+S323T、A339S+Q299Y+V206L、A339S+Q299Y+Y29 5F, A339S+Q345R+Q365S, A339S+Q345R+R320K, A339S+Q345R+R458K, A339S+Q345R+S323T, A339S+Q345R+V206L, A339S+Q345R+Y295F, A339S+Q365S+R3 20K, A339S+Q365S+R458K, A339S+Q365S+S323T, A339S+Q365S+V206L, A339S+Q365S+Y295F, A339S+R320K+R458K, A339S+R320K+S323T, A339S+R320K+V 206L, A339S+R320K+Y295F, A339S+R458K+S323T, A339S+R458K+V206L, A339S+R458K+Y295F, A339S+S323T+V206L, A339S+S323T+Y295F, A339S+V206L +Y295F、G109A+G149A+G182T、G109A+G149A+H1*、G109A+G149A+I9M、G109A+G149A+K391A、G109A+G149A+M202L、G109A+G149A+N16Y、G109A+G149A+N19 5F, G109A+G149A+N54S, G109A+G149A+Q169E, G109A+G149A+Q169E, G109A+G149A+Q172K, G109A+G149A+Q299Y, G109A+G149A+Q345R, G109A+G149A+Q36 5S、G109A+G149A+R320K、G109A+G149A+R458K、G109A+G149A+S323T、G109A+G149A+V206L、G109A+G149A+Y295F、G109A+G182T+H1*、G109A+G182T+I9M、<h2 style=";text-align:left;direction:ltr">G109A+G182T+K391A, G109A+G182T+M202L, G109A+G182T+N16Y, G109A+G182T+N195F, G109A+G182T+N54S, G109A+G182T+Q169E, G109A+G182T+Q169E G109A+G182T+Q172K, G109A+G182T+Q299Y, G109A+G182T+Q345R, G109A+G182T+Q365S, G109A+G182T+R320K, G109A+G182T+R458K, G109A+G182T+S3 23T, G109A+G182T+V206L, G109A+G182T+Y295F, G109A+H1*+I9M, G109A+H1*+K391A, G109A+H1*+M202L, G109A+H1*+N16Y, G109A+H1*+N195F, G109A+ H1*+N54S、G109A+H1*+Q169E、G109A+H1*+Q169E、G109A+H1*+Q172K、G109A +H1*+Q299Y、G109A+H1*+Q345R、G109A+H1*+Q365S、G109A+H1*+R320K、G10 9A+H1*+R458K、G109A+H1*+S323T、G109A+H1*+V206L、G109A+H1*+Y295F、G109A+I9M+K391A、G109A+I9M+M202L、G109A+I9M+N16Y、G109A+I9M+N195F G109A+I9M+N54S, G109A+I9M+Q169E, G109A+I9M+Q169E, G109A+I9M+Q172K, G109A+I9M+Q299Y, G109A+I9M+Q345R, G109A+I9M+Q365S, G109A+I9M+R 320K, G109A+I9M+R458K, G109A+I9M+S323T, G109A+I9M+V206L, G109A+I9M+Y295F, G109A+K391A+M202L, G109A+K391A+N16Y, G109A+K391A+N195F, G 109A+K391A+N54S、G109A+K391A+Q169E、G109A+K391A+Q169E、G109A+K391A+Q172K、G109A+K391A+Q299Y、G109A+K391A+Q345R、G109A+K391A+Q365S、<h2 style=";text-align:left;direction:ltr">G109A+K391A+R320K, G109A+K391A+R458K, G109A+K391A+S323T, G109A+K391A+V206L, G109A+K391A+Y295F, G109A+M202L+N16Y, G109A+M202L+N195F G109A+M202L+N54S, G109A+M202L+Q169E, G109A+M202L+Q169E, G109A+M202L+Q172K, G109A+M202L+Q299Y, G109A+M202L+Q345R, G109A+M202L+Q365S 、G109A+M202L+R320K、G109A+M202L+R458K、G109A+M202L+S323T、G109A+M 202L+V206L、G109A+M202L+Y295F、G109A+N16Y+N195F、G109A+N16Y+N54S、G 109A+N16Y+Q169E、G109A+N16Y+Q169E、G109A+N16Y+Q172K、G109A+N16Y+Q 299Y、G109A+N16Y+Q345R、G109A+N16Y+Q365S、G109A+N16Y+R320K、G109A+N 16Y+R458K, G109A+N16Y+S323T, G109A+N16Y+V206L, G109A+N16Y+Y295F, G109A+N195F+N54S, G109A+N195F+Q169E, G109A+N195F+Q169E, G109A+N195 F+Q172K、G109A+N195F+Q299Y、G109A+N195F+Q345R、G109A+N195F+Q365S、 G109A+N195F+R320K、G109A+N195F+R458K、G109A+N195F+S323T、G109A+N19 5F+V206L、G109A+N195F+Y295F、G109A+N54S+Q169E、G109A+N54S+Q169E、G109A+N54S+Q172K、G109A+N54S+Q299Y、G109A+N54S+Q345R、G109A+N54S+Q3 65S, G109A+N54S+R320K, G109A+N54S+R458K, G109A+N54S+S323T, G109A+N54S+V206L, G109A+N54S+Y295F, G109A+Q169E+Q169E, G109A+Q169E+Q172K,<h2 style=";text-align:left;direction:ltr">G109A+Q169E+Q299Y、G109A+Q169E+Q345R、G109A+Q169E+Q365S、G109A+Q169E+R320K、G109A+Q169E+R458K、G109A+Q169E+S323T、G109A+Q169E+V206L、G109A+Q169E+Y295F、G10、<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">9A+Q169E+Q172K、G109A+Q169E+Q299Y、G109A+Q169E+Q345R、G109A+Q169E+Q365S、G109A+Q169E+R320K、G109A+Q169E+R458K、G109A+Q169E+S323T、G 109A+Q169E+V206L、G109A+Q169E+Y295F、G109A+Q172K+Q299Y、G109A+Q172K+Q345R、G109A+Q172K+Q365S、G109A+Q172K+R320K、G109A+Q172K+R458K、 G109A+Q172K+S323T, G109A+Q172K+V206L, G109A+Q172K+Y295F, G109A+Q299Y+Q345R, G109A+Q299Y+Q365S, G109A+Q299Y+R320K, G109A+Q299Y+R458K G109A+Q299Y+S323T, G109A+Q299Y+V206L, G109A+Q299Y+Y295F, G109A+Q345R+Q365S, G109A+Q345R+R320K, G109A+Q345R+R458K, G109A+Q345R+S323 T、G109A+Q345R+V206L、G109A+Q345R+Y295F、G109A+Q365S+R320K、G109A+ Q365S+R458K、G109A+Q365S+S323T、G109A+Q365S+V206L、G109A+Q365S+Y29 5F、G109A+R320K+R458K、G109A+R320K+S323T、G109A+R320K+V206L、G109A+R320K+Y295F、G109A+R458K+S323T、G109A+R458K+V206L、G109A+R458K+Y2 95F, G109A+S323T+V206L, G109A+S323T+Y295F, G109A+V206L+Y295F, G149A+G182T+H1*, G149A+G182T+I9M, G149A+G182T+K391A, G149A+G182T+M202L G149A+G182T+N16Y, G149A+G182T+N195F, G149A+G182T+N54S, G149A+G182T+Q169E, G149A+G182T+Q169E, G149A+G182T+Q172K, G149A+G182T+Q299Y<h2 style=";text-align:left;direction:ltr">G149A+G182T+Q345R、G149A+G182T+Q365S、G149A+G182T+R320K、G149A+G182T+R458K、G149A+G182T+S323T、G149A+G182T+V206L、G149A+G182T+Y29 5F, G149A+H1*+I9M, G149A+H1*+K391A, G149A+H1*+M202L, G149A+H1*+N16Y, G149A+H1*+N195F, G149A+H1*+N54S, G149A+H1*+Q169E, G149A+H1*+Q1 69E、G149A+H1*+Q172K、G149A+H1*+Q299Y、G149A+H1*+Q345R、G149A+H1* +Q365S、G149A+H1*+R320K、G149A+H1*+R458K、G149A+H1*+S323T、G149A+H 1*+V206L、G149A+H1*+Y295F、G149A+I9M+K391A、G149A+I9M+M202L、G149A+I9M+N16Y、G149A+I9M+N195F、G149A+I9M+N54S、G149A+I9M+Q169E、G149A +I9M+Q169E、G149A+I9M+Q172K、G149A+I9M+Q299Y、G149A+I9M+Q345R、G149A+I9M+Q365S、G149A+I9M+R320K、G149A+I9M+R458K、G149A+I9M+S323T、 G149A+I9M+V206L, G149A+I9M+Y295F, G149A+K391A+M202L, G149A+K391A+N16Y, G149A+K391A+N195F, G149A+K391A+N54S, G149A+K391A+Q169E, G14 9A+K391A+Q169E、G149A+K391A+Q172K、G149A+K391A+Q299Y、G149A+K391A+Q345R、G149A+K391A+Q365S、G149A+K391A+R320K、G149A+K391A+R458K、 G149A+K391A+S323T、G149A+K391A+V206L、G149A+K391A+Y295F、G149A+M202L+N16Y、G149A+M202L+N195F、G149A+M202L+N54S、G149A+M202L+Q169E、<h2 style=";text-align:left;direction:ltr">G149A+M202L+Q169E, G149A+M202L+Q172K, G149A+M202L+Q299Y, G149A+M202L+Q345R, G149A+M202L+Q365S, G149A+M202L+R320K, G149A+M202L+R458K G149A+M202L+S323T, G149A+M202L+V206L, G149A+M202L+Y295F, G149A+N16Y+N195F, G149A+N16Y+N54S, G149A+N16Y+Q169E, G149A+N16Y+Q169E, G14 9A+N16Y+Q172K、G149A+N16Y+Q299Y、G149A+N16Y+Q345R、G149A+N16Y+Q365S、G149A+N16Y+R320K、G149A+N16Y+R458K、G149A+N16Y+S323T、G149A+N16 Y+V206L、G149A+N16Y+Y295F、G149A+N195F+N54S、G149A+N195F+Q169E、G149A+N195F+Q169E、G149A+N195F+Q172K、G149A+N195F+Q299Y、G149A+N195F +Q345R, G149A+N195F+Q365S, G149A+N195F+R320K, G149A+N195F+R458K, G149A+N195F+S323T, G149A+N195F+V206L, G149A+N195F+Y295F, G149A+N54S +Q169E, G149A+N54S+Q169E, G149A+N54S+Q172K, G149A+N54S+Q299Y, G149A+N54S+Q345R, G149A+N54S+Q365S, G149A+N54S+R320K, G149A+N54S+R458K 、G149A+N54S+S323T、G149A+N54S+V206L、G149A+N54S+Y295F、G149A+Q169 E+Q169E、G149A+Q169E+Q172K、G149A+Q169E+Q299Y、G149A+Q169E+Q345R、G 149A+Q169E+Q365S、G149A+Q169E+R320K、G149A+Q169E+R458K、G149A+Q169E+S323T、G149A+Q169E+V206L、G149A+Q169E+Y295F、G149A+Q169E+Q172K、<h2 style=";text-align:left;direction:ltr">G149A+Q169E+Q299Y、G149A+Q169E+Q345R、G149A+Q169E+Q365S、G149A+Q169E+R320K、G149A+Q169E+R458K、G149A+Q169E+S323T、G149A+Q169E+V206 L, G149A+Q169E+Y295F, G149A+Q172K+Q299Y, G149A+Q172K+Q345R, G149A+Q172K+Q365S, G149A+Q172K+R320K, G149A+Q172K+R458K, G149A+Q172K+S32 3T、G149A+Q172K+V206L、G149A+Q172K+Y295F、G149A+Q299Y+Q345R、G149A +Q299Y+Q365S、G149A+Q299Y+R320K、G149A+Q299Y+R458K、G149A+Q299Y+S 323T, G149A+Q299Y+V206L, G149A+Q299Y+Y295F, G149A+Q345R+Q365S, G149A+Q345R+R320K, G149A+Q345R+R458K, G149A+Q345R+S323T, G149A+Q345R+ V206L, G149A+Q345R+Y295F, G149A+Q365S+R320K, G149A+Q365S+R458K, G149A+Q365S+S323T, G149A+Q365S+V206L, G149A+Q365S+Y295F, G149A+R320 K+R458K、G149A+R320K+S323T、G149A+R320K+V206L、G149A+R320K+Y295F、 G149A+R458K+S323T、G149A+R458K+V206L、G149A+R458K+Y295F、G149A+S32 3T+V206L、G149A+S323T+Y295F、G149A+V206L+Y295F、G182T+H1*+I9M、G18 2T+H1*+K391A、G182T+H1*+M202L、G182T+H1*+N16Y、G182T+H1*+N195F、G1 82T+H1*+N54S、G182T+H1*+Q169E、G182T+H1*+Q169E、G182T+H1*+Q172K、G 182T+H1*+Q299Y、G182T+H1*+Q345R、G182T+H1*+Q365S、G182T+H1*+R320K、<h2 style=";text-align:left;direction:ltr">G182T+H1*+R458K、G182T+H1*+S323T、G182T+H1*+V206L、G182T+H1*+Y295F、G182T+I9M+K391A、G182T+I9M+M202L、G182T+I9M+N16Y、G182T+I9M+N1 95F, G182T+I9M+N54S, G182T+I9M+Q169E, G182T+I9M+Q169E, G182T+I9M+Q172K, G182T+I9M+Q299Y, G182T+I9M+Q345R, G182T+I9M+Q365S, G182T+I9M +R320K, G182T+I9M+R458K, G182T+I9M+S323T, G182T+I9M+V206L, G182T+I9M+Y295F, G182T+K391A+M202L, G182T+K391A+N16Y, G182T+K391A+N195F G182T+K391A+N54S, G182T+K391A+Q169E, G182T+K391A+Q169E, G182T+K391A+Q172K, G182T+K391A+Q299Y, G182T+K391A+Q345R, G182T+K391A+Q365 S、G182T+K391A+R320K、G182T+K391A+R458K、G182T+K391A+S323T、G182T +K391A+V206L、G182T+K391A+Y295F、G182T+M202L+N16Y、G182T+M202L+N1 95F、G182T+M202L+N54S、G182T+M202L+Q169E、G182T+M202L+Q169E、G182T +M202L+Q172K、G182T+M202L+Q299Y、G182T+M202L+Q345R、G182T+M202L+Q 365S、G182T+M202L+R320K、G182T+M202L+R458K、G182T+M202L+S323T、G1 82T+M202L+V206L、G182T+M202L+Y295F、G182T+N16Y+N195F、G182T+N16Y+ N54S、G182T+N16Y+Q169E、G182T+N16Y+Q169E、G182T+N16Y+Q172K、G182T+ N16Y+Q299Y、G182T+N16Y+Q345R、G182T+N16Y+Q365S、G182T+N16Y+R320K、G182T+N16Y+R458K, G182T+N16Y+S323T, G182T+N16Y+V206L, G182T+N16Y+Y295F, G182T+N195F+N54S, G182T+N195F+Q169E, G182T+N195F+Q169E, G182T+N195F+Q172K, G182T+N195F+Q, 299Y、G182T+N195F+Q345R、G182T+N195F+Q365S、G182T+N195F+R320K、G182T+N195F+R458K、G182T+N195F+S323T、G182T+N195F+V206L、G182T+N195F+Y295F、G182T+N54S+Q169E、G182T+N54S+Q169E、G182T+N54S+Q172K、G182T+N54S+Q299Y、G182T+N54S+Q345R、G182T+N54S+Q365S、G182T+N54S+R320K、G182T+N54S+R458K、G182T+N54S+S323T、G182T+N54S+V206L、G182T+N54S+Y295F、G182T+Q169E+Q169E、G182T+Q169E+Q172K、G182T+Q169E+Q299Y、G182T+Q169E+Q345R、G182T+Q169E+Q365S、G182T+Q169E+R320K、G182T+Q169E+R458K、G182T+Q169E+S323T、G182T+Q169E+V206L、G182T+Q169E+Y295F、G182T+Q169E+Q172K、G182T+Q169E+Q299Y、G182T+Q169E+Q345R、G182T+Q169E+Q365S、G182T+Q169E+R320K、G182T+Q169E+R458K、G182T+Q169E+S323T、G182T+Q169E+V206L、G182T+Q169E+Y295F、G182T+Q172K+Q299Y、G182T+Q172K+Q345R、G182T+Q172K+Q365S、G182T+Q172K+R320K、G182T+Q172K+R458K、G182T+Q172K+S323T、G182T+Q172K+V206L、G182T+Q172K+Y295F、G182T+Q299Y+Q345R、G182T+Q299Y+Q365S、G182T+Q299Y+R320K、G182T+Q299Y+R458K、G182T+Q299Y+S323T、G182T+Q299Y+V206L、G182T+Q299Y+Y295F、G182T+Q345R+Q365S、G182T+Q345R+R320K、G182T+Q345R+R458K、<h2 style=";text-align:left;direction:ltr">G182T+Q345R+S323T、G182T+Q345R+V206L、G182T+Q345R+Y295F、G182T+Q 365S+R320K、G182T+Q365S+R458K、G182T+Q365S+S323T、G182T+Q365S+V20 6L、G182T+Q365S+Y295F、G182T+R320K+R458K、G182T+R320K+S323T、G182T +R320K+V206L、G182T+R320K+Y295F、G182T+R458K+S323T、G182T+R458K+V 206L, G182T+R458K+Y295F, G182T+S323T+V206L, G182T+S323T+Y295F, G182T+V206L+Y295F, H1*+I9M+K391A, H1*+I9M+M202L, H1*+I9M+N16Y, H1*+I9 M+N195F、H1*+I9M+N54S、H1*+I9M+Q169E、H1*+I9M+Q169E、H1*+I9M+Q172K 、H1*+I9M+Q299Y、H1*+I9M+Q345R、H1*+I9M+Q365S、H1*+I9M+R320K、H1*+I 9M+R458K、H1*+I9M+S323T、H1*+I9M+V206L、H1*+I9M+Y295F、H1*+K391A+ M202L、H1*+K391A+N16Y、H1*+K391A+N195F、H1*+K391A+N54S、H1*+K391A+ Q169E、H1*+K391A+Q169E、H1*+K391A+Q172K、H1*+K391A+Q299Y、H1*+K391 A+Q345R、H1*+K391A+Q365S、H1*+K391A+R320K、H1*+K391A+R458K、H1*+K3 91A+S323T、H1*+K391A+V206L、H1*+K391A+Y295F、H1*+M202L+N16Y、H1*+M 202L+N195F、H1*+M202L+N54S、H1*+M202L+Q169E、H1*+M202L+Q169E、H1*+ M202L+Q172K、H1*+M202L+Q299Y、H1*+M202L+Q345R、H1*+M202L+Q365S、H1 *+M202L+R320K、H1*+M202L+R458K、H1*+M202L+S323T、H1*+M202L+V206L、H1*+M202L+Y295F、H1*+N16Y+N195F、H1*+N16Y+N54S、H1*+N16Y+Q169E、H1*+N16Y+Q169E、H1*+N16Y+Q172K、H1*+N16Y+Q299Y、H1*+N16Y+Q345R、H1*+N16Y+Q365S、H1*+N16Y+R320K、H1*+N16Y+R458K、H1*+N16Y+S323T、H1*+N16Y+V206L、H1*+N16Y+Y295F、H1*+N195F+N54S、H1*+N195F+Q169E、H1*+N195F+Q169E、H1*+N195F+Q172K、H1*+N195F+Q299Y、H1*+N195F+Q345R、H1*+N195F+Q365S、H1*+N195F+R320K、H1*+N195F+R458K、H1*+N195F+S323T、H1*+N195F+V206L、H1*+N195F+Y295F、H1*+N54S+Q169E、H1*+N54S+Q169E、H1*+N54S+Q172K、H1*+N54S+Q299Y、H1*+N54S+Q345R、H1*+N54S+Q365S、H1*+N54S+R320K、H1*+N54S+R458K、H1*+N54S+S323T、H1*+N54S+V206L、H1*+N54S+Y295F、H1*+Q169E+Q169E、H1*+Q169E+Q172K、H1*+Q169E+Q299Y、H1*+Q169E+Q345R、H1*+Q169E+Q365S、H1*+Q169E+R320K、H1*+Q169E+R458K、H1*+Q169E+S323T、H1*+Q169E+V206L、H1*+Q169E+Y295F、H1*+Q169E+Q172K、H1*+Q169E+Q299Y、H1*+Q169E+Q345R、H1*+Q169E+Q365S、H1*+Q169E+R320K、H1*+Q169E+R458K、H1*+Q169E+S323T、H1*+Q169E+V206L、H1*+Q169E+Y295F、H1*+Q172K+Q299Y、H1*+Q172K+Q345R、H1*+Q172K+Q365S、H1*+Q172K+R320K、H1*+Q172K+R458K、H1*+Q172K+S323T、H1*+Q172K+V206L、H1*+Q172K+Y295F、<h2 style=";text-align:left;direction:ltr">H1*+Q299Y+Q345R、H1*+Q299Y+Q365S、H1*+Q299Y+R320K、H1*+Q299Y+R458 K、H1*+Q299Y+S323T、H1*+Q299Y+V206L、H1*+Q299Y+Y295F、H1*+Q345R+Q3 65S、H1*+Q345R+R320K、H1*+Q345R+R458K、H1*+Q345R+S323T、H1*+Q345R+ V206L、H1*+Q345R+Y295F、H1*+Q365S+R320K、H1*+Q365S+R458K、H1*+Q365S +S323T、H1*+Q365S+V206L、H1*+Q365S+Y295F、H1*+R320K+R458K、H1*+R32 0K+S323T、H1*+R320K+V206L、H1*+R320K+Y295F、H1*+R458K+S323T、H1*+R 458K+V206L, H1*+R458K+Y295F, H1*+S323T+V206L, H1*+S323T+Y295F, H1*+V206L+Y295F, I9M+K391A+M202L, I9M+K391A+N16Y, I9M+K391A+N195F, I9M +K391A+N54S、I9M+K391A+Q169E、I9M+K391A+Q169E、I9M+K391A+Q172K、I9M+K391A+Q299Y、I9M+K391A+Q345R、I9M+K391A+Q365S、I9M+K391A+R320K、 I9M+K391A+R458K, I9M+K391A+S323T, I9M+K391A+V206L, I9M+K391A+Y295F, I9M+M202L+N16Y, I9M+M202L+N195F, I9M+M202L+N54S, I9M+M202L+Q169E I9M+M202L+Q169E, I9M+M202L+Q172K, I9M+M202L+Q299Y, I9M+M202L+Q345R, I9M+M202L+Q365S, I9M+M202L+R320K, I9M+M202L+R458K, I9M+M202L+S3 23T, I9M+M202L+V206L, I9M+M202L+Y295F, I9M+N16Y+N195F, I9M+N16Y+N54S, I9M+N16Y+Q169E, I9M+N16Y+Q169E, I9M+N16Y+Q172K, I9M+N16Y+Q299Y,<h2 style=";text-align:left;direction:ltr">I9M+N16Y+Q345R, I9M+N16Y+Q365S, I9M+N16Y+R320K, I9M+N16Y+R458K, I9M+N16Y+S323T, I9M+N16Y+V206L, I9M+N16Y+Y295F, I9M+N195F+N54S, I9M +N195F+Q169E, I9M+N195F+Q169E, I9M+N195F+Q172K, I9M+N195F+Q299Y, I9M+N195F+Q345R, I9M+N195F+Q365S, I9M+N195F+R320K, I9M+N195F+R458K I9M+N195F+S323T, I9M+N195F+V206L, I9M+N195F+Y295F, I9M+N54S+Q169E, I9M+N54S+Q169E, I9M+N54S+Q172K, I9M+N54S+Q299Y, I9M+N54S+Q345R I9M+N54S+Q365S, I9M+N54S+R320K, I9M+N54S+R458K, I9M+N54S+S323T, I9M+N54S+V206L, I9M+N54S+Y295F, I9M+Q169E+Q169E, I9M+Q169E+Q172K, I 9M+Q169E+Q299Y、I9M+Q169E+Q345R、I9M+Q169E+Q365S、I9M+Q169E+R320 K、I9M+Q169E+R458K、I9M+Q169E+S323T、I9M+Q169E+V206L、I9M+Q169E+Y2 95F, I9M+Q169E+Q172K, I9M+Q169E+Q299Y, I9M+Q169E+Q345R, I9M+Q169E+Q365S, I9M+Q169E+R320K, I9M+Q169E+R458K, I9M+Q169E+S323T, I9M+Q169 E+V206L、I9M+Q169E+Y295F、I9M+Q172K+Q299Y、I9M+Q172K+Q345R、I9M+Q172K+Q365S、I9M+Q172K+R320K、I9M+Q172K+R458K、I9M+Q172K+S323T、I9M+ Q172K+V206L, I9M+Q172K+Y295F, I9M+Q299Y+Q345R, I9M+Q299Y+Q365S, I9M+Q299Y+R320K, I9M+Q299Y+R458K, I9M+Q299Y+S323T, I9M+Q299Y+V206L,<h2 style=";text-align:left;direction:ltr">I9M+Q299Y+Y295F、I9M+Q345R+Q365S、I9M+Q345R+R320K、I9M+Q345R+R458K、I9M+Q345R+S323T、I9M+Q345R+V206L、I9M+Q345R+Y295F、I9M+Q365S+R320K、I9M+Q365S+R458K、I9M+Q365S+S323T、I9M、<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">+Q365S+V206L、I9M+Q365S+Y295F、I9M+R320K+R458K、I9M+R320K+S323T、I9M+R320K+V206L、I9M+R320K+Y295F、I9M+R458K+S323T、I9M+R458K+V206L I9M+R458K+Y295F, I9M+S323T+V206L, I9M+S323T+Y295F, I9M+V206L+Y295F, K391A+M202L+N16Y, K391A+M202L+N195F, K391A+M202L+N54S, K391A+M 202L+Q169E, K391A+M202L+Q169E, K391A+M202L+Q172K, K391A+M202L+Q299Y, K391A+M202L+Q345R, K391A+M202L+Q365S, K391A+M202L+R320K, K391A +M202L+R458K、K391A+M202L+S323T、K391A+M202L+V206L、K391A+M202L+Y295F、K391A+N16Y+N195F、K391A+N16Y+N54S、K391A+N16Y+Q169E、K391A+N 16Y+Q169E、K391A+N16Y+Q172K、K391A+N16Y+Q299Y、K391A+N16Y+Q345R、K 391A+N16Y+Q365S、K391A+N16Y+R320K、K391A+N16Y+R458K、K391A+N16Y+S 323T, K391A+N16Y+V206L, K391A+N16Y+Y295F, K391A+N195F+N54S, K391A+N195F+Q169E, K391A+N195F+Q169E, K391A+N195F+Q172K, K391A+N195F+Q2 99Y, K391A+N195F+Q345R, K391A+N195F+Q365S, K391A+N195F+R320K, K391A+N195F+R458K, K391A+N195F+S323T, K391A+N195F+V206L, K391A+N195F+ Y295F、K391A+N54S+Q169E、K391A+N54S+Q169E、K391A+N54S+Q172K、K391A+N54S+Q299Y、K391A+N54S+Q345R、K391A+N54S+Q365S、K391A+N54S+R320K、<h2 style=";text-align:left;direction:ltr">K391A+N54S+R458K、K391A+N54S+S323T、K391A+N54S+V206L、K391A+N54S +Y295F、K391A+Q169E+Q169E、K391A+Q169E+Q172K、K391A+Q169E+Q299Y、K 391A+Q169E+Q345R, K391A+Q169E+Q365S, K391A+Q169E+R320K, K391A+Q169E+R458K, K391A+Q169E+S323T, K391A+Q169E+V206L, K391A+Q169E+Y295 F、K391A+Q169E+Q172K、K391A+Q169E+Q299Y、K391A+Q169E+Q345R、K391A +Q169E+Q365S、K391A+Q169E+R320K、K391A+Q169E+R458K、K391A+Q169E+S 323T, K391A+Q169E+V206L, K391A+Q169E+Y295F, K391A+Q172K+Q299Y, K391A+Q172K+Q345R, K391A+Q172K+Q365S, K391A+Q172K+R320K, K391A+Q172K +R458K, K391A+Q172K+S323T, K391A+Q172K+V206L, K391A+Q172K+Y295F, K391A+Q299Y+Q345R, K391A+Q299Y+Q365S, K391A+Q299Y+R320K, K391A+Q2 99Y+R458K, K391A+Q299Y+S323T, K391A+Q299Y+V206L, K391A+Q299Y+Y295F, K391A+Q345R+Q365S, K391A+Q345R+R320K, K391A+Q345R+R458K, K391A +Q345R+S323T、K391A+Q345R+V206L、K391A+Q345R+Y295F、K391A+Q365S+ R320K、K391A+Q365S+R458K、K391A+Q365S+S323T、K391A+Q365S+V206L、K3 91A+Q365S+Y295F、K391A+R320K+R458K、K391A+R320K+S323T、K391A+R320K+V206L、K391A+R320K+Y295F、K391A+R458K+S323T、K391A+R458K+V206L、K391A+R458K+Y295F、K391A+S323T+V206L、K391A+S323T+Y295F、K391A+V206L+Y295F、M202L+N16Y+N195F、M202L+N16Y+N54S、M202L+N16Y+Q169E、M202L+N16Y+Q169E、M202L+N16Y+Q172K、M202L+N16Y+Q299Y、M202L+N16Y+Q345RM202L+N16Y+Q365S、M202L+N16Y+R320K、M202L+N16Y+R458K、M202L+N16Y+S323T、M202L+N16Y+V206L、M202L+N16Y+Y295F、M202L+N195F+N54S、M202L+N195F+Q169E、M202L+N195F+Q169E、M202L+N195F+Q172K、M202L+N195F+Q299Y、M202L+N195F+Q345R、M202L+N195F+Q365S、M202L+N195F+R320K、M202L+N195F+R458K、M202L+N195F+S323T、M202L+N195F+V206L、M202L+N195F+Y295F、M202L+N54S+Q169E、M202L+N54S+Q169E、M202L+N54S+Q172K、M202L+N54S+Q299Y、M202L+N54S+Q345R、M202L+N54S+Q365S、M202L+N54S+R320K、M202L+N54S+R458K、M202L+N54S+S323T、M202L+N54S+V206L、M202L+N54S+Y295F、M202L+Q169E+Q169E、M202L+Q169E+Q172K、M202L+Q169E+Q299Y、M202L+Q169E+Q345R、M202L+Q169E+Q365S、M202L+Q169E+R320K、M202L+Q169E+R458K、M202L+Q169E+S323T、M202L+Q169E+V206L、M202L+Q169E+Y295F、M202L+Q169E+Q172K、M202L+Q169E+Q299Y、M202L+Q169E+Q345R、M202L+Q169E+Q365S、M202L+Q169E+R320K、M202L+Q169E+R458K、M202L+Q169E+S323T、M202L+Q169E+V206L、M202L+Q169E+Y295F、M202L+Q172K+Q299Y、M202L+Q172K+Q345R、M202L+Q172K+Q365S、M202L+Q172K+R320K、M202L+Q172K+R458K、M202L+Q172K+S323T、M202L+Q172K+V206L、M202L+Q172K+Y295F、M202L+Q299Y+Q345R、M202L+Q299Y+Q365S、M202L+Q299Y+R320K、M202L+Q299Y+R458K、M202L+Q299Y+S323T、M202L+Q299Y+V206L、M202L+Q299Y+Y295F、M202L+Q345R+Q365S、M202L+Q345R+R320K、M202L+Q345R+R458K、M202L+Q345R+S323T、M202L+Q345R+V206L、M202L+Q345R+Y295F、M202L+Q365S+R320K、M202L+Q365S+R458K、M202L+Q365S+S323T、M202L+Q365S+V206L、M202L+Q365S+Y295F、M202L+R320K+R458K、M202L+R320K+S323T、M202L+R320K+V206L、M202L+R320K+Y295F、M202L+R458K+S323T、M202L+R458K+V206L、M202L+R458K+Y295F、M202L+S323T+V206L、M202L+S323T+Y295F、M202L+V206L+Y295F、N16Y+N195F+N54S、N16Y+N195F+Q169E、N16Y+N195F+Q169E、N16Y+N195F+Q172K、N16Y+N195F+Q299Y、N16Y+N195F+Q345R、N16Y+N195F+Q365S、N16Y+N195F+R320K、N16Y+N195F+R458K、N16Y+N195F+S323T、N16Y+N195F+V206L、N16Y+N195F+Y295F、N16Y+N54S+Q169E、N16Y+N54S+Q169E、N16Y+N54S+Q172K、N16Y+N54S+Q299Y、N16Y+N54S+Q345R、N16Y+N54S+Q365S、N16Y+N54S+R320K、N16Y+N54S+R458K、N16Y+N54S+S323T、N16Y+N54S+V206L、N16Y+N54S+Y295F、N16Y+Q169E+Q169E、N16Y+Q169E+Q172K、N16Y+Q169E+Q299Y、N16Y+Q169E+Q345R、N16Y+Q169E+Q365S、N16Y+Q169E+R320K、N16Y+Q169E+R458K、N16Y+Q169E+S323T、N16Y+Q169E+V206L、N16Y+Q169E+Y295F、N16Y+Q169E+Q172K、N16Y+Q169E+Q299Y、N16Y+Q169E+Q345R、N16Y+Q169E+Q365S、N16Y+Q169E+R320K、N16Y+Q169E+R458K、N16Y+Q169E+S323T、N16Y+Q169E+V206L、N16Y+Q169E+Y295F、N16Y+Q172K+Q299Y、N16Y+Q172K+Q345R、N16Y+Q172K+Q365S、N16Y+Q172K+R320K、N16Y+Q172K+R458K、N16Y+Q172K+S323T、N16Y+Q172K+V206L、N16Y+Q172K+Y295F、N16Y+Q299Y+Q345R、N16Y+Q299Y+Q365S、N16Y+Q299Y+R320K、N16Y+Q299Y+R458K、N16Y+Q299Y+S323T、N16Y+Q299Y+V206L、N16Y+Q299Y+Y295F、N16Y+Q345R+Q365S、N16Y+Q345R+R320K、N16Y+Q345R+R458K、N16Y+Q345R+S323T、N16Y+Q345R+V206L、N16Y+Q345R+Y295F、N16Y+Q365S+R320K、N16Y+Q365S+R458K、N16Y+Q365S+S323T、N16Y+Q365S+V206L、N16Y+Q365S+Y295F、N16Y+R320K+R458K、N16Y+R320K+S323T、N16Y+R320K+V206L、N16Y+R320K+Y295F、N16Y+R458K+S323T、N16Y+R458K+V206L、N16Y+R458K+Y295F、N16Y+S323T+V206L、N16Y+S323T+Y295F、N16Y+V206L+Y295F、<h2 style=";text-align:left;direction:ltr">N195F+N54S+Q169E, N195F+N54S+Q169E, N195F+N54S+Q172K, N195F+N54S+Q299Y, N195F+N54S+Q345R, N195F+N54S+Q365S, N195F+N54S+R320K, N195F+N54S+R458K, N195F+N54<h2 style=";text-align:left;direction:ltr"> S+S323T、N195F+N54S+V206L、N195F+N54S+Y295F、N195F+Q169E+Q169E、N195F+Q169E+Q172K、N195F+Q169E+Q299Y、N195F+Q169E+Q345R、N195F+Q169E+Q365S、N195F+Q169E+R320K、N195F+Q169E+R458K、N195F+Q169E+S323T、N195F+Q169E+V206L、N195F+Q169E+Y295F、N195F+Q169E+Q172K、N195F+Q169E+Q299Y、N195F+Q169E+Q345R、N195F+Q169E+Q365S、N195F+Q169E+R320K、N195F+Q169E+R458K、N195F+Q169E+S323T、N195F+Q169E+V206L、N195F+Q169E+Y295F、N195F+Q172K+Q299Y、N195F+Q172K+Q345R、N195F+Q172K+Q365S、N195F+Q172K+R320K、N195F+Q172K+R458K、N195F+Q172K+S323T、N195F+Q172K+V206L、N195F+Q172K+Y295F、N195F+Q299Y+Q345R、N195F+Q299Y+Q365S、N195F+Q299Y+R320K、N195F+Q299Y+R458K、N195F+Q299Y+S323T、N195F+Q299Y+V206L、N195F+Q299Y+Y295F、N195F+Q345R+Q365S、N195F+Q345R+R320K、N195F+Q345R+R458K、N195F+Q345R+S323T、N195F+Q345R+V206L、N195F+Q345R+Y295F、N195F+Q365S+R320K、N195F+Q365S+R458K、N195F+Q365S+S323T、N195F+Q365S+V206LN195F+Q365S+Y295F、N195F+R320K+R458K、N195F+R320K+S323T、N195F+R320K+V206L、N195F+R320K+Y295F、N195F+R458K+S323T、N195F+R458K+V206L、N195F+R458K+Y295F、N195F+S323T+V206L、<h2 style=";text-align:left;direction:ltr">N195F+S323T+Y295F、N195F+V206L+Y295F、N54S+Q169E+Q169E、N54S+Q16 9E+Q172K、N54S+Q169E+Q299Y、N54S+Q169E+Q345R、N54S+Q169E+Q365S、N5 4S+Q169E+R320K、N54S+Q169E+R458K、N54S+Q169E+S323T、N54S+Q169E+V2 06L、N54S+Q169E+Y295F、N54S+Q169E+Q172K、N54S+Q169E+Q299Y、N54S+Q1 69E+Q345R、N54S+Q169E+Q365S、N54S+Q169E+R320K、N54S+Q169E+R458K、 N54S+Q169E+S323T、N54S+Q169E+V206L、N54S+Q169E+Y295F、N54S+Q172K+ Q299Y, N54S+Q172K+Q345R, N54S+Q172K+Q365S, N54S+Q172K+R320K, N54S+Q172K+R458K, N54S+Q172K+S323T, N54S+Q172K+V206L, N54S+Q172K+Y295F 、N54S+Q299Y+Q345R、N54S+Q299Y+Q365S、N54S+Q299Y+R320K、N54S+Q299 Y+R458K、N54S+Q299Y+S323T、N54S+Q299Y+V206L、N54S+Q299Y+Y295F、N54 S+Q345R+Q365S、N54S+Q345R+R320K、N54S+Q345R+R458K、N54S+Q345R+S32 3T、N54S+Q345R+V206L、N54S+Q345R+Y295F、N54S+Q365S+R320K、N54S+Q36 5S+R458K、N54S+Q365S+S323T、N54S+Q365S+V206L、N54S+Q365S+Y295F、N5 4S+R320K+R458K、N54S+R320K+S323T、N54S+R320K+V206L、N54S+R320K+Y2 95F, N54S+R458K+S323T, N54S+R458K+V206L, N54S+R458K+Y295F, N54S+S323T+V206L, N54S+S323T+Y295F, N54S+V206L+Y295F, Q169E+Q169E+Q172K,Q169E+Q169E+Q299Y、Q169E+Q169E+Q345R、Q169E+Q169E+Q365S、Q169E+Q169E+R320K、Q169E+Q169E+R458K、Q169E+Q169E+S323T、Q169E+Q169E+V206L、Q169E+Q169E+Y295F、Q169E+Q172K+Q299Y、Q169E+Q172K+Q345R、Q169E+Q172K+Q365S、Q169E+Q172K+R320K、Q169E+Q172K+R458K、Q169E+Q172K+S323T、Q169E+Q172K+V206L、Q169E+Q172K+Y295F、Q169E+Q299Y+Q345R、Q169E+Q299Y+Q365S、Q169E+Q299Y+R320K、Q169E+Q299Y+R458K、Q169E+Q299Y+S323T、Q169E+Q299Y+V206L、Q169E+Q299Y+Y295F、Q169E+Q345R+Q365S、Q169E+Q345R+R320K、Q169E+Q345R+R458K、Q169E+Q345R+S323T、Q169E+Q345R+V206L、Q169E+Q345R+Y295F、Q169E+Q365S+R320K、Q169E+Q365S+R458K、Q169E+Q365S+S323T、Q169E+Q365S+V206L、Q169E+Q365S+Y295F、Q169E+R320K+R458K、Q169E+R320K+S323T、Q169E+R320K+V206L、Q169E+R320K+Y295F、Q169E+R458K+S323T、Q169E+R458K+V206L、Q169E+R458K+Y295F、Q169E+S323T+V206L、Q169E+S323T+Y295F、Q169E+V206L+Y295F、Q169E+Q172K+Q299Y、Q169E+Q172K+Q345R、Q169E+Q172K+Q365S、Q169E+Q172K+R320K、Q169E+Q172K+R458K、Q169E+Q172K+S323T、Q169E+Q172K+V206L、Q169E+Q172K+Y295F、Q169E+Q299Y+Q345R、Q169E+Q299Y+Q365S、Q169E+Q299Y+R320K、Q169E+Q299Y+R458K、Q169E+Q299Y+S323T、Q169E+Q299Y+V206L、Q169E+Q299Y+Y295F、Q169E+Q345R+Q365S、Q169E+Q345R+R320K、Q169E+Q345R+R458K、Q169E+Q345R+S323T、Q169E+Q345R+V206L、Q169E+Q345R+Y295F、Q169E+Q365S+R320K、Q169E+Q365S+R458K、Q169E+Q365S+S323T、Q169E+Q365S+V206L、Q169E+Q365S+Y295F、Q169E+R320K+R458K、Q169E+R320K+S323T、Q169E+R320K+V206L、Q169E+R320K+Y295F、Q169E+R458K+S323T、Q169E+R458K+V206L、Q169E+R458K+Y295F、Q169E+S323T+V206L、Q169E+S323T+Y295F、Q169E+V206L+Y295F、Q172K+Q299Y+Q345R、Q172K+Q299Y+Q365S、Q172K+Q299Y+R320K、Q172K+Q299Y+R458K、Q172K+Q299Y+S323T、Q172K+Q299Y+V206L、Q172K+Q299Y+Y295F、Q172K+Q345R+Q365S、Q172K+Q345R+R320K、Q172K+Q345R+R458K、Q172K+Q345R+S323T、Q172K+Q345R+V206L、Q172K+Q345R+Y295F、Q172K+Q365S+R320K、Q172K+Q365S+R458K、Q172K+Q365S+S323T、Q172K+Q365S+V206L、Q172K+Q365S+Y295F、Q172K+R320K+R458K、Q172K+R320K+S323T、Q172K+R320K+V206L、Q172K+R320K+Y295F、Q172K+R458K+S323T、Q172K+R458K+V206L、Q172K+R458K+Y295F、Q172K+S323T+V206L、Q172K+S323T+Y295F、Q172K+V206L+Y295F、Q299Y+Q345R+Q365S、Q299Y+Q345R+R320K、Q299Y+Q345R+R458K, Q299Y+Q345R+S323T, Q299Y+Q345R+V206L, Q299Y+Q3 45R+Y295F, Q299Y+Q365S+R320K, Q299Y+Q365S+R458K, Q299Y+Q365S+S323 T, Q299Y+Q365S+V206L, Q299Y+Q365S+Y295F, Q299Y+R320K+R458K, Q299Y+ R320K+S323T, Q299Y+R320K+V206L, Q299Y+R320K+Y295F, Q299Y+R458K+S3 23T, Q299Y+R458K+V206L, Q299Y+R458K+Y295F, Q299Y+S323T+V206L, Q299 Y+S323T+Y295F, Q299Y+V206L+Y295F, Q345R+Q365S+R320K, Q345R+Q365S+ R458K, Q345R+Q365S+S323T, Q345R+Q365S+V206L, Q345R+Q365S+Y295F, Q3 45R+R320K+R458K, Q345R+R320K+S323T, Q345R+R320K+V206L, Q345R+R320 K+Y295F, Q345R+R458K+S323T, Q345R+R458K+V206L, Q345R+R458K+Y295F, Q345R+S323T+V206L, Q345R+S323T+Y295F, Q345R+V206L+Y295F, Q365S+R3 20K+R458K, Q365S+R320K+S323T, Q365S+R320K+V206L, Q365S+R320K+Y295 F, Q365S+R458K+S323T, Q365S+R458K+V206L, Q365S+R458K+Y295F, Q365S+ S323T+V206L, Q365S+S323T+Y295F, Q365S+V206L+Y295F, R320K+R458K+S323T, R320K+R458K+V206L, R320K+R458K+Y295F, R320K+S323T+V206L, R320K+S323T+Y295F, R320K+V206L+Y295F, R458K+S323T+V206L, R458K+S323T+Y295F, R458K+V206L+Y295F, S323T+V206L+Y295F,It has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, but less than 100%, sequence identity to the polypeptides of SEQ ID NOs: 1 to 17.

[0280] In one aspect, the variant has the following modifications at positions corresponding to the following positions, using SEQ ID NO: 1 for numbering: <h2 style=";text-align:left;direction:ltr">A174*+A339S+G109A+G149A、A174*+A339S+G109A+G182T、A174*+A339S+G109A+H1*、A174*+A339S+G109A+I9M、A174*+A339S+G109A+K391A、A174*+A3 39S+G109A+M202L、A174*+A339S+G109A+N16Y、A174*+A339S+G109A+N195F、A174*+A339S+G109A+N54S、A174*+A339S+G109A+Q169E、A174*+A339S+G1 09A+Q169E、A174*+A339S+G109A+Q172K、A174*+A339S+G109A+Q299Y、A174*+A339S+G109A+Q345R、A174*+A339S+G109A+Q365S、A174*+A339S+G109A+ R320K, A174*+A339S+G109A+R458K, A174*+A339S+G109A+S323T, A174*+A339S+G109A+V206L, A174*+A339S+G109A+Y295F, A174*+A339S+G149A+G182 T、A174*+A339S+G149A+H1*、A174*+A339S+G149A+I9M、A174*+A339S+G149 A+K391A、A174*+A339S+G149A+M202L、A174*+A339S+G149A+N16Y、A174*+A 339S+G149A+N195F、A174*+A339S+G149A+N54S、A174*+A339S+G149A+Q169E、A174*+A339S+G149A+Q169E、A174*+A339S+G149A+Q172K、A174*+A339S+ G149A+Q299Y、A174*+A339S+G149A+Q345R、A174*+A339S+G149A+Q365S、A174*+A339S+G149A+R320K、A174*+A339S+G149A+R458K、A174*+A339S+G149 A+S323T、A174*+A339S+G149A+V206L、A174*+A339S+G149A+Y295F、A174*+A339S+G182T+H1*、A174*+A339S+G182T+I9M、A174*+A339S+G182T+K391A、<h2 style=";text-align:left;direction:ltr">A174*+A339S+G182T+M202L、A174*+A339S+G182T+N16Y、A174*+A339S+G182T+N195F、A174*+A339S+G182T+N54S、A174*+A339S+G182T+Q169E、A174* +A339S+G182T+Q169E、A174*+A339S+G182T+Q172K、A174*+A339S+G182T+Q299Y、A174*+A339S+G182T+Q345R、A174*+A339S+G182T+Q365S、A174*+A33 9S+G182T+R320K、A174*+A339S+G182T+R458K、A174*+A339S+G182T+S323T 、A174*+A339S+G182T+V206L、A174*+A339S+G182T+Y295F、A174*+A339S+H 1*+I9M、A174*+A339S+H1*+K391A、A174*+A339S+H1*+M202L、A174*+A339S+H1*+N16Y、A174*+A339S+H1*+N195F、A174*+A339S+H1*+N54S、A174*+A33 9S+H1*+Q169E、A174*+A339S+H1*+Q169E、A174*+A339S+H1*+Q172K、A174*+A339S+H1*+Q299Y、A174*+A339S+H1*+Q345R、A174*+A339S+H1*+Q365S、 A174*+A339S+H1*+R320K, A174*+A339S+H1*+R458K, A174*+A339S+H1*+S323T, A174*+A339S+H1*+V206L, A174*+A339S+H1*+Y295F, A174*+A339S+I9 M+K391A、A174*+A339S+I9M+M202L、A174*+A339S+I9M+N16Y、A174*+A339S+I9M+N195F、A174*+A339S+I9M+N54S、A174*+A339S+I9M+Q169E、A174*+A3 39S+I9M+Q169E、A174*+A339S+I9M+Q172K、A174*+A339S+I9M+Q299Y、A174*+A339S+I9M+Q345R、A174*+A339S+I9M+Q365S、A174*+A339S+I9M+R320K、<h2 style=";text-align:left;direction:ltr">A174*+A339S+I9M+R458K、A174*+A339S+I9M+S323T、A174*+A339S+I9M+V206L、A174*+A339S+I9M+Y295F、A174*+A339S+K391A+M202L、A174*+A339S +K391A+N16Y、A174*+A339S+K391A+N195F、A174*+A339S+K391A+N54S、A174*+A339S+K391A+Q169E、A174*+A339S+K391A+Q169E、A174*+A339S+K391 A+Q172K、A174*+A339S+K391A+Q299Y、A174*+A339S+K391A+Q345R、A174*+A339S+K391A+Q365S、A174*+A339S+K391A+R320K、A174*+A339S+K391A+R 458K, A174*+A339S+K391A+S323T, A174*+A339S+K391A+V206L, A174*+A339S+K391A+Y295F, A174*+A339S+M202L+N16Y, A174*+A339S+M202L+N195F A174*+A339S+M202L+N54S、A174*+A339S+M202L+Q169E、A174*+A339S+M202L+Q169E、A174*+A339S+M202L+Q172K、A174*+A339S+M202L+Q299Y、A174 *+A339S+M202L+Q345R、A174*+A339S+M202L+Q365S、A174*+A339S+M202L+R320K、A174*+A339S+M202L+R458K、A174*+A339S+M202L+S323T、A174*+A 339S+M202L+V206L、A174*+A339S+M202L+Y295F、A174*+A339S+N16Y+N195F、A174*+A339S+N16Y+N54S、A174*+A339S+N16Y+Q169E、A174*+A339S+N1 6Y+Q169E、A174*+A339S+N16Y+Q172K、A174*+A339S+N16Y+Q299Y、A174*+A339S+N16Y+Q345R、A174*+A339S+N16Y+Q365S、A174*+A339S+N16Y+R320K、<h2 style=";text-align:left;direction:ltr">A174*+A339S+N16Y+R458K、A174*+A339S+N16Y+S323T、A174*+A339S+N16Y+V206L、A174*+A339S+N16Y+Y295F、A174*+A339S+N195F+N54S、A174*+A33 9S+N195F+Q169E、A174*+A339S+N195F+Q169E、A174*+A339S+N195F+Q172K、A174*+A339S+N195F+Q299Y、A174*+A339S+N195F+Q345R、A174*+A339S+N 195F+Q365S、A174*+A339S+N195F+R320K、A174*+A339S+N195F+R458K、A174*+A339S+N195F+S323T、A174*+A339S+N195F+V206L、A174*+A339S+N195F +Y295F、A174*+A339S+N54S+Q169E、A174*+A339S+N54S+Q169E、A174*+A339S+N54S+Q172K、A174*+A339S+N54S+Q299Y、A174*+A339S+N54S+Q345R、A1 74*+A339S+N54S+Q365S、A174*+A339S+N54S+R320K、A174*+A339S+N54S+R458K、A174*+A339S+N54S+S323T、A174*+A339S+N54S+V206L、A174*+A339S +N54S+Y295F、A174*+A339S+Q169E+Q169E、A174*+A339S+Q169E+Q172K、A174*+A339S+Q169E+Q299Y、A174*+A339S+Q169E+Q345R、A174*+A339S+Q169 E+Q365S、A174*+A339S+Q169E+R320K、A174*+A339S+Q169E+R458K、A174*+A339S+Q169E+S323T、A174*+A339S+Q169E+V206L、A174*+A339S+Q169E+Y2 95F, A174*+A339S+Q169E+Q172K, A174*+A339S+Q169E+Q299Y, A174*+A339S+Q169E+Q345R, A174*+A339S+Q169E+Q365S, A174*+A339S+Q169E+R320K,<h2 style=";text-align:left;direction:ltr">A174*+A339S+Q169E+R458K, A174*+A339S+Q169E+S323T, A174*+A339S+Q169E+V206L, A174*+A339S+Q169E+Y295F, A174*+A339S+Q172K+Q299Y, A17 4*+A339S+Q172K+Q345R、A174*+A339S+Q172K+Q365S、A174*+A339S+Q172K+R320K、A174*+A339S+Q172K+R458K、A174*+A339S+Q172K+S323T、A174*+ A339S+Q172K+V206L、A174*+A339S+Q172K+Y295F、A174*+A339S+Q299Y+Q345R、A174*+A339S+Q299Y+Q365S、A174*+A339S+Q299Y+R320K、A174*+A33 9S+Q299Y+R458K、A174*+A339S+Q299Y+S323T、A174*+A339S+Q299Y+V206L、A174*+A339S+Q299Y+Y295F、A174*+A339S+Q345R+Q365S、A174*+A339S+ Q345R+R320K、A174*+A339S+Q345R+R458K、A174*+A339S+Q345R+S323T、A174*+A339S+Q345R+V206L、A174*+A339S+Q345R+Y295F、A174*+A339S+Q36 5S+R320K、A174*+A339S+Q365S+R458K、A174*+A339S+Q365S+S323T、A174*+A339S+Q365S+V206L、A174*+A339S+Q365S+Y295F、A174*+A339S+R320K+ R458K, A174*+A339S+R320K+S323T, A174*+A339S+R320K+V206L, A174*+A339S+R320K+Y295F, A174*+A339S+R458K+S323T, A174*+A339S+R458K+V20 6L、A174*+A339S+R458K+Y295F、A174*+A339S+S323T+V206L、A174*+A339 S+S323T+Y295F、A174*+A339S+V206L+Y295F、A174*+G109A+G149A+G182T、<h2 style=";text-align:left;direction:ltr">A174*+G109A+G149A+H1*、A174*+G109A+G149A+I9M、A174*+G109A+G149A+K391A、A174*+G109A+G149A+M202L、A174*+G109A+G149A+N16Y、A174*+G109A+G149A+N195F、A174*+G109A+G149A+N54S、A174*+G109A+G14、<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">9A+Q169E、A174*+G109A+G149A+Q169E、A174*+G109A+G149A+Q172K、A174*+G109A+G149A+Q299Y、A174*+G109A+G149A+Q345R、A174*+G109A+G149A+Q3 65S, A174*+G109A+G149A+R320K, A174*+G109A+G149A+R458K, A174*+G109A+G149A+S323T, A174*+G109A+G149A+V206L, A174*+G109A+G149A+Y295F, A 174*+G109A+G182T+H1*、A174*+G109A+G182T+I9M、A174*+G109A+G182T+K391A、A174*+G109A+G182T+M202L、A174*+G109A+G182T+N16Y、A174*+G109A +G182T+N195F、A174*+G109A+G182T+N54S、A174*+G109A+G182T+Q169E、A174*+G109A+G182T+Q169E、A174*+G109A+G182T+Q172K、A174*+G109A+G182T +Q299Y、A174*+G109A+G182T+Q345R、A174*+G109A+G182T+Q365S、A174*+G109A+G182T+R320K、A174*+G109A+G182T+R458K、A174*+G109A+G182T+S323 T、A174*+G109A+G182T+V206L、A174*+G109A+G182T+Y295F、A174*+G109A+ H1*+I9M、A174*+G109A+H1*+K391A、A174*+G109A+H1*+M202L、A174*+G109A +H1*+N16Y、A174*+G109A+H1*+N195F、A174*+G109A+H1*+N54S、A174*+G10 9A+H1*+Q169E、A174*+G109A+H1*+Q169E、A174*+G109A+H1*+Q172K、A174*+ G109A+H1*+Q299Y、A174*+G109A+H1*+Q345R、A174*+G109A+H1*+Q365S、A174*+G109A+H1*+R320K、A174*+G109A+H1*+R458K、A174*+G109A+H1*+S323T、<h2 style=";text-align:left;direction:ltr">A174*+G109A+H1*+V206L、A174*+G109A+H1*+Y295F、A174*+G109A+I9M+K391A、A174*+G109A+I9M+M202L、A174*+G109A+I9M+N16Y、A174*+G109A+I9 M+N195F、A174*+G109A+I9M+N54S、A174*+G109A+I9M+Q169E、A174*+G109A +I9M+Q169E、A174*+G109A+I9M+Q172K、A174*+G109A+I9M+Q299Y、A174*+G 109A+I9M+Q345R, A174*+G109A+I9M+Q365S, A174*+G109A+I9M+R320K, A174*+G109A+I9M+R458K, A174*+G109A+I9M+S323T, A174*+G109A+I9M+V206L A174*+G109A+I9M+Y295F, A174*+G109A+K391A+M202L, A174*+G109A+K391A+N16Y, A174*+G109A+K391A+N195F, A174*+G109A+K391A+N54S, A174*+G 109A+K391A+Q169E、A174*+G109A+K391A+Q169E、A174*+G109A+K391A+Q172K、A174*+G109A+K391A+Q299Y、A174*+G109A+K391A+Q345R、A174*+G109 A+K391A+Q365S、A174*+G109A+K391A+R320K、A174*+G109A+K391A+R458K、 A174*+G109A+K391A+S323T、A174*+G109A+K391A+V206L、A174*+G109A+K3 91A+Y295F、A174*+G109A+M202L+N16Y、A174*+G109A+M202L+N195F、A174*+G109A+M202L+N54S、A174*+G109A+M202L+Q169E、A174*+G109A+M202L+Q1 69E、A174*+G109A+M202L+Q172K、A174*+G109A+M202L+Q299Y、A174*+G109A+M202L+Q345R、A174*+G109A+M202L+Q365S、A174*+G109A+M202L+R320K、<h2 style=";text-align:left;direction:ltr">A174*+G109A+M202L+R458K, A174*+G109A+M202L+S323T, A174*+G109A+M202L+V206L, A174*+G109A+M202L+Y295F, A174*+G109A+N16Y+N195F, A17 4*+G109A+N16Y+N54S、A174*+G109A+N16Y+Q169E、A174*+G109A+N16Y+Q1 69E、A174*+G109A+N16Y+Q172K、A174*+G109A+N16Y+Q299Y、A174*+G109A+ N16Y+Q345R、A174*+G109A+N16Y+Q365S、A174*+G109A+N16Y+R320K、A174 *+G109A+N16Y+R458K、A174*+G109A+N16Y+S323T、A174*+G109A+N16Y+V20 6L、A174*+G109A+N16Y+Y295F、A174*+G109A+N195F+N54S、A174*+G109A+ N195F+Q169E、A174*+G109A+N195F+Q169E、A174*+G109A+N195F+Q172K、A1 74*+G109A+N195F+Q299Y、A174*+G109A+N195F+Q345R、A174*+G109A+N195F+Q365S、A174*+G109A+N195F+R320K、A174*+G109A+N195F+R458K、A174 *+G109A+N195F+S323T、A174*+G109A+N195F+V206L、A174*+G109A+N195F+Y295F、A174*+G109A+N54S+Q169E、A174*+G109A+N54S+Q169E、A174*+G10 9A+N54S+Q172K、A174*+G109A+N54S+Q299Y、A174*+G109A+N54S+Q345R、A174*+G109A+N54S+Q365S、A174*+G109A+N54S+R320K、A174*+G109A+N54S+ R458K, A174*+G109A+N54S+S323T, A174*+G109A+N54S+V206L, A174*+G109A+N54S+Y295F, A174*+G109A+Q169E+Q169E, A174*+G109A+Q169E+Q172K,<h2 style=";text-align:left;direction:ltr">A174*+G109A+Q169E+Q299Y、A174*+G109A+Q169E+Q345R、A174*+G109A+Q 169E+Q365S、A174*+G109A+Q169E+R320K、A174*+G109A+Q169E+R458K、A17 4*+G109A+Q169E+S323T、A174*+G109A+Q169E+V206L、A174*+G109A+Q169E+Y295F、A174*+G109A+Q169E+Q172K、A174*+G109A+Q169E+Q299Y、A174*+ G109A+Q169E+Q345R、A174*+G109A+Q169E+Q365S、A174*+G109A+Q169E+R 320K、A174*+G109A+Q169E+R458K、A174*+G109A+Q169E+S323T、A174*+G10 9A+Q169E+V206L、A174*+G109A+Q169E+Y295F、A174*+G109A+Q172K+Q299Y、A174*+G109A+Q172K+Q345R、A174*+G109A+Q172K+Q365S、A174*+G109A+ Q172K+R320K, A174*+G109A+Q172K+R458K, A174*+G109A+Q172K+S323T, A174*+G109A+Q172K+V206L, A174*+G109A+Q172K+Y295F, A174*+G109A+Q29 9Y+Q345R、A174*+G109A+Q299Y+Q365S、A174*+G109A+Q299Y+R320K、A174*+G109A+Q299Y+R458K、A174*+G109A+Q299Y+S323T、A174*+G109A+Q299Y+ V206L, A174*+G109A+Q299Y+Y295F, A174*+G109A+Q345R+Q365S, A174*+G109A+Q345R+R320K, A174*+G109A+Q345R+R458K, A174*+G109A+Q345R+S32 3T、A174*+G109A+Q345R+V206L、A174*+G109A+Q345R+Y295F、A174*+G109 A+Q365S+R320K、A174*+G109A+Q365S+R458K、A174*+G109A+Q365S+S323T、<h2 style=";text-align:left;direction:ltr">A174*+G109A+Q365S+V206L、A174*+G109A+Q365S+Y295F、A174*+G109A+R320K+R458K、A174*+G109A+R320K+S323T、A174*+G109A+R320K+V206L、A174 *+G109A+R320K+Y295F、A174*+G109A+R458K+S323T、A174*+G109A+R458K+V206L、A174*+G109A+R458K+Y295F、A174*+G109A+S323T+V206L、A174*+G10 9A+S323T+Y295F、A174*+G109A+V206L+Y295F、A174*+G149A+G182T+H1*、A174*+G149A+G182T+I9M、A174*+G149A+G182T+K391A、A174*+G149A+G182T +M202L、A174*+G149A+G182T+N16Y、A174*+G149A+G182T+N195F、A174*+G149A+G182T+N54S、A174*+G149A+G182T+Q169E、A174*+G149A+G182T+Q169E、 A174*+G149A+G182T+Q172K, A174*+G149A+G182T+Q299Y, A174*+G149A+G182T+Q345R, A174*+G149A+G182T+Q365S, A174*+G149A+G182T+R320K, A174 *+G149A+G182T+R458K、A174*+G149A+G182T+S323T、A174*+G149A+G182T+ V206L、A174*+G149A+G182T+Y295F、A174*+G149A+H1*+I9M、A174*+G149A+H 1*+K391A、A174*+G149A+H1*+M202L、A174*+G149A+H1*+N16Y、A174*+G149 A+H1*+N195F、A174*+G149A+H1*+N54S、A174*+G149A+H1*+Q169E、A174*+G 149A+H1*+Q169E、A174*+G149A+H1*+Q172K、A174*+G149A+H1*+Q299Y、A174*+G149A+H1*+Q345R、A174*+G149A+H1*+Q365S、A174*+G149A+H1*+R320K、<h2 style=";text-align:left;direction:ltr">A174*+G149A+H1*+R458K、A174*+G149A+H1*+S323T、A174*+G149A+H1*+V206L、A174*+G149A+H1*+Y295F、A174*+G149A+I9M+K391A、A174*+G149A+I9M+M202L、A174*+G149A+I9M+N16Y、A174*+G149A+I9M、<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">+N195F、A174*+G149A+I9M+N54S、A174*+G149A+I9M+Q169E、A174*+G149A+I9M+Q169E、A174*+G149A+I9M+Q172K、A174*+G149A+I9M+Q299Y、A174*+G 149A+I9M+Q345R、A174*+G149A+I9M+Q365S、A174*+G149A+I9M+R320K、A174*+G149A+I9M+R458K、A174*+G149A+I9M+S323T、A174*+G149A+I9M+V206 L、A174*+G149A+I9M+Y295F、A174*+G149A+K391A+M202L、A174*+G149A+K391A+N16Y、A174*+G149A+K391A+N195F、A174*+G149A+K391A+N54S、A174* +G149A+K391A+Q169E、A174*+G149A+K391A+Q169E、A174*+G149A+K391A+Q172K、A174*+G149A+K391A+Q299Y、A174*+G149A+K391A+Q345R、A174*+G1 49A+K391A+Q365S、A174*+G149A+K391A+R320K、A174*+G149A+K391A+R458K、A174*+G149A+K391A+S323T、A174*+G149A+K391A+V206L、A174*+G149A +K391A+Y295F、A174*+G149A+M202L+N16Y、A174*+G149A+M202L+N195F、A174*+G149A+M202L+N54S、A174*+G149A+M202L+Q169E、A174*+G149A+M202 L+Q169E、A174*+G149A+M202L+Q172K、A174*+G149A+M202L+Q299Y、A174*+G149A+M202L+Q345R、A174*+G149A+M202L+Q365S、A174*+G149A+M202L+R 320K, A174*+G149A+M202L+R458K, A174*+G149A+M202L+S323T, A174*+G149A+M202L+V206L, A174*+G149A+M202L+Y295F, A174*+G149A+N16Y+N195F,<h2 style=";text-align:left;direction:ltr">A174*+G149A+N16Y+N54S、A174*+G149A+N16Y+Q169E、A174*+G149A+N16Y +Q169E、A174*+G149A+N16Y+Q172K、A174*+G149A+N16Y+Q299Y、A174*+G1 49A+N16Y+Q345R、A174*+G149A+N16Y+Q365S、A174*+G149A+N16Y+R320K、A174*+G149A+N16Y+R458K、A174*+G149A+N16Y+S323T、A174*+G149A+N16Y +V206L、A174*+G149A+N16Y+Y295F、A174*+G149A+N195F+N54S、A174*+G149A+N195F+Q169E、A174*+G149A+N195F+Q169E、A174*+G149A+N195F+Q172 K、A174*+G149A+N195F+Q299Y、A174*+G149A+N195F+Q345R、A174*+G149A +N195F+Q365S、A174*+G149A+N195F+R320K、A174*+G149A+N195F+R458K、A 174*+G149A+N195F+S323T、A174*+G149A+N195F+V206L、A174*+G149A+N195F+Y295F、A174*+G149A+N54S+Q169E、A174*+G149A+N54S+Q169E、A174*+ G149A+N54S+Q172K、A174*+G149A+N54S+Q299Y、A174*+G149A+N54S+Q345R、A174*+G149A+N54S+Q365S、A174*+G149A+N54S+R320K、A174*+G149A+N5 4S+R458K、A174*+G149A+N54S+S323T、A174*+G149A+N54S+V206L、A174*+ G149A+N54S+Y295F、A174*+G149A+Q169E+Q169E、A174*+G149A+Q169E+Q17 2K, A174*+G149A+Q169E+Q299Y, A174*+G149A+Q169E+Q345R, A174*+G149A+Q169E+Q365S, A174*+G149A+Q169E+R320K, A174*+G149A+Q169E+R458K,<h2 style=";text-align:left;direction:ltr">A174*+G149A+Q169E+S323T, A174*+G149A+Q169E+V206L, A174*+G149A+Q169E+Y295F, A174*+G149A+Q169E+Q172K, A174*+G149A+Q169E+Q299Y, A17 4*+G149A+Q169E+Q345R、A174*+G149A+Q169E+Q365S、A174*+G149A+Q169E+R320K、A174*+G149A+Q169E+R458K、A174*+G149A+Q169E+S323T、A174*+ G149A+Q169E+V206L、A174*+G149A+Q169E+Y295F、A174*+G149A+Q172K+Q299Y、A174*+G149A+Q172K+Q345R、A174*+G149A+Q172K+Q365S、A174*+G14 9A+Q172K+R320K、A174*+G149A+Q172K+R458K、A174*+G149A+Q172K+S323T、A174*+G149A+Q172K+V206L、A174*+G149A+Q172K+Y295F、A174*+G149A+ Q299Y+Q345R、A174*+G149A+Q299Y+Q365S、A174*+G149A+Q299Y+R320K、A174*+G149A+Q299Y+R458K、A174*+G149A+Q299Y+S323T、A174*+G149A+Q29 9Y+V206L、A174*+G149A+Q299Y+Y295F、A174*+G149A+Q345R+Q365S、A174*+G149A+Q345R+R320K、A174*+G149A+Q345R+R458K、A174*+G149A+Q345R+ S323T, A174*+G149A+Q345R+V206L, A174*+G149A+Q345R+Y295F, A174*+G149A+Q365S+R320K, A174*+G149A+Q365S+R458K, A174*+G149A+Q365S+S32 3T、A174*+G149A+Q365S+V206L、A174*+G149A+Q365S+Y295F、A174*+G149 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style=";text-align:left;direction:ltr">A174*+G182T+Q299Y+S323T、A174*+G182T+Q299Y+V206L、A174*+G182T+Q 299Y+Y295F、A174*+G182T+Q345R+Q365S、A174*+G182T+Q345R+R320K、A1 74*+G182T+Q345R+R458K、A174*+G182T+Q345R+S323T、A174*+G182T+Q345R+V206L、A174*+G182T+Q345R+Y295F、A174*+G182T+Q365S+R320K、A174* +G182T+Q365S+R458K、A174*+G182T+Q365S+S323T、A174*+G182T+Q365S+ V206L、A174*+G182T+Q365S+Y295F、A174*+G182T+R320K+R458K、A174*+G 182T+R320K+S323T、A174*+G182T+R320K+V206L、A174*+G182T+R320K+Y2 95F、A174*+G182T+R458K+S323T、A174*+G182T+R458K+V206L、A174*+G182 T+R458K+Y295F、A174*+G182T+S323T+V206L、A174*+G182T+S323T+Y295F、A174*+G182T+V206L+Y295F、A174*+H1*+I9M+K391A、A174*+H1*+I9M+M2 02L、A174*+H1*+I9M+N16Y、A174*+H1*+I9M+N195F、A174*+H1*+I9M+N54S 、A174*+H1*+I9M+Q169E、A174*+H1*+I9M+Q169E、A174*+H1*+I9M+Q172K、A 174*+H1*+I9M+Q299Y、A174*+H1*+I9M+Q345R、A174*+H1*+I9M+Q365S、A174*+H1*+I9M+R320K、A174*+H1*+I9M+R458K、A174*+H1*+I9M+S323T、A17 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style=";text-align:left;direction:ltr">A174*+H1*+Q299Y+S323T、A174*+H1*+Q299Y+V206L、A174*+H1*+Q299Y+Y 295F、A174*+H1*+Q345R+Q365S、A174*+H1*+Q345R+R320K、A174*+H1*+Q34 5R+R458K、A174*+H1*+Q345R+S323T、A174*+H1*+Q345R+V206L、A174*+H1 *+Q345R+Y295F、A174*+H1*+Q365S+R320K、A174*+H1*+Q365S+R458K、A174 *+H1*+Q365S+S323T、A174*+H1*+Q365S+V206L、A174*+H1*+Q365S+Y295F 、A174*+H1*+R320K+R458K、A174*+H1*+R320K+S323T、A174*+H1*+R320K+V 206L、A174*+H1*+R320K+Y295F、A174*+H1*+R458K+S323T、A174*+H1*+R45 8K+V206L、A174*+H1*+R458K+Y295F、A174*+H1*+S323T+V206L、A174*+H1* +S323T+Y295F、A174*+H1*+V206L+Y295F、A174*+I9M+K391A+M202L、A174*+I9M+K391A+N16Y、A174*+I9M+K391A+N195F、A174*+I9M+K391A+N54S、A1 74*+I9M+K391A+Q169E、A174*+I9M+K391A+Q169E、A174*+I9M+K391A+Q172K、A174*+I9M+K391A+Q299Y、A174*+I9M+K391A+Q345R、A174*+I9M+K391A +Q365S、A174*+I9M+K391A+R320K、A174*+I9M+K391A+R458K、A174*+I9M+K391A+S323T、A174*+I9M+K391A+V206L、A174*+I9M+K391A+Y295F、A174*+ 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style=";text-align:left;direction:ltr">A174*+R458K+V206L+Y295F, A174*+S323T+V206L+Y295F, A339S+G109A+G149A+G182T, A339S+G109A+G149A+H1*, A339S+G109A+G149A+I9M, A339S+G109A+G149A+K391A, A339S+G109A+G149A+M202L, A339S+G109A+G149A+N16Y, A339S+G1,<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">09A+G149A+N195F、A339S+G109A+G149A+N54S、A339S+G109A+G149A+Q169E、A339S+G109A+G149A+Q169E、A339S+G109A+G149A+Q172K、A339S+G109A+ G149A+Q299Y, A339S+G109A+G149A+Q345R, A339S+G109A+G149A+Q365S, A339S+G109A+G149A+R320K, A339S+G109A+G149A+R458K, A339S+G109A+G149 A+S323T, A339S+G109A+G149A+V206L, A339S+G109A+G149A+Y295F, A339S+G109A+G182T+H1*, A339S+G109A+G182T+I9M, A339S+G109A+G182T+K391A A339S+G109A+G182T+M202L, A339S+G109A+G182T+N16Y, A339S+G109A+G182T+N195F, A339S+G109A+G182T+N54S, A339S+G109A+G182T+Q169E, A339S +G109A+G182T+Q169E、A339S+G109A+G182T+Q172K、A339S+G109A+G182T+Q299Y、A339S+G109A+G182T+Q345R、A339S+G109A+G182T+Q365S、A339S+G1 09A+G182T+R320K, A339S+G109A+G182T+R458K, A339S+G109A+G182T+S323T, A339S+G109A+G182T+V206L, A339S+G109A+G182T+Y295F, A339S+G109A+ H1*+I9M, A339S+G109A+H1*+K391A, A339S+G109A+H1*+M202L, A339S+G109A+H1*+N16Y, A339S+G109A+H1*+N195F, A339S+G109A+H1*+N54S, A339S+G1 09A+H1*+Q169E、A339S+G109A+H1*+Q169E、A339S+G109A+H1*+Q172K、A339S+G109A+H1*+Q299Y、A339S+G109A+H1*+Q345R、A339S+G109A+H1*+Q365S、<h2 style=";text-align:left;direction:ltr">A339S+G109A+H1*+R320K, A339S+G109A+H1*+R458K, A339S+G109A+H1*+S323T, A339S+G109A+H1*+V206L, A339S+G109A+H1*+Y295F, A339S+G109A+I 9M+K391A, A339S+G109A+I9M+M202L, A339S+G109A+I9M+N16Y, A339S+G109A+I9M+N195F, A339S+G109A+I9M+N54S, A339S+G109A+I9M+Q169E, A339S+ G109A+I9M+Q169E, A339S+G109A+I9M+Q172K, A339S+G109A+I9M+Q299Y, A339S+G109A+I9M+Q345R, A339S+G109A+I9M+Q365S, A339S+G109A+I9M+R32 0K, A339S+G109A+I9M+R458K, A339S+G109A+I9M+S323T, A339S+G109A+I9M+V206L, A339S+G109A+I9M+Y295F, A339S+G109A+K391A+M202L, A339S+G1 09A+K391A+N16Y、A339S+G109A+K391A+N195F、A339S+G109A+K391A+N54S、A339S+G109A+K391A+Q169E、A339S+G109A+K391A+Q169E、A339S+G109A+K 391A+Q172K, A339S+G109A+K391A+Q299Y, A339S+G109A+K391A+Q345R, A339S+G109A+K391A+Q365S, A339S+G109A+K391A+R320K, A339S+G109A+K391 A+R458K, A339S+G109A+K391A+S323T, A339S+G109A+K391A+V206L, A339S+G109A+K391A+Y295F, A339S+G109A+M202L+N16Y, A339S+G109A+M202L+N1 95F, A339S+G109A+M202L+N54S, A339S+G109A+M202L+Q169E, A339S+G109A+M202L+Q169E, A339S+G109A+M202L+Q172K, A339S+G109A+M202L+Q299Y,<h2 style=";text-align:left;direction:ltr">A339S+G109A+M202L+Q345R, A339S+G109A+M202L+Q365S, A339S+G109A+M202L+R320K, A339S+G109A+M202L+R458K, A339S+G109A+M202L+S323T, A3 39S+G109A+M202L+V206L, A339S+G109A+M202L+Y295F, A339S+G109A+N16Y+N195F, A339S+G109A+N16Y+N54S, A339S+G109A+N16Y+Q169E, A339S+G10 9A+N16Y+Q169E、A339S+G109A+N16Y+Q172K、A339S+G109A+N16Y+Q299Y、A339S+G109A+N16Y+Q345R、A339S+G109A+N16Y+Q365S、A339S+G109A+N16Y+ R320K, A339S+G109A+N16Y+R458K, A339S+G109A+N16Y+S323T, A339S+G109A+N16Y+V206L, A339S+G109A+N16Y+Y295F, A339S+G109A+N195F+N54S, A3 39S+G109A+N195F+Q169E, A339S+G109A+N195F+Q169E, A339S+G109A+N195F+Q172K, A339S+G109A+N195F+Q299Y, A339S+G109A+N195F+Q345R, A339S +G109A+N195F+Q365S, A339S+G109A+N195F+R320K, A339S+G109A+N195F+R458K, A339S+G109A+N195F+S323T, A339S+G109A+N195F+V206L, A339S+G1 09A+N195F+Y295F、A339S+G109A+N54S+Q169E、A339S+G109A+N54S+Q169E、A339S+G109A+N54S+Q172K、A339S+G109A+N54S+Q299Y、A339S+G109A+N54 S+Q345R, A339S+G109A+N54S+Q365S, A339S+G109A+N54S+R320K, A339S+G109A+N54S+R458K, A339S+G109A+N54S+S323T, A339S+G109A+N54S+V206L,<h2 style=";text-align:left;direction:ltr">A339S+G109A+N54S+Y295F, A339S+G109A+Q169E+Q169E, A339S+G109A+Q169E+Q172K, A339S+G109A+Q169E+Q299Y, A339S+G109A+Q169E+Q345R, A33 9S+G109A+Q169E+Q365S、A339S+G109A+Q169E+R320K、A339S+G109A+Q169E+R458K、A339S+G109A+Q169E+S323T、A339S+G109A+Q169E+V206L、A339S+ G109A+Q169E+Y295F, A339S+G109A+Q169E+Q172K, A339S+G109A+Q169E+Q299Y, A339S+G109A+Q169E+Q345R, A339S+G109A+Q169E+Q365S, A339S+G10 9A+Q169E+R320K, A339S+G109A+Q169E+R458K, A339S+G109A+Q169E+S323T, A339S+G109A+Q169E+V206L, A339S+G109A+Q169E+Y295F, A339S+G109A+ Q172K+Q299Y, A339S+G109A+Q172K+Q345R, A339S+G109A+Q172K+Q365S, A339S+G109A+Q172K+R320K, A339S+G109A+Q172K+R458K, A339S+G109A+Q17 2K+S323T, A339S+G109A+Q172K+V206L, A339S+G109A+Q172K+Y295F, A339S+G109A+Q299Y+Q345R, A339S+G109A+Q299Y+Q365S, A339S+G109A+Q299Y+ R320K, A339S+G109A+Q299Y+R458K, A339S+G109A+Q299Y+S323T, A339S+G109A+Q299Y+V206L, A339S+G109A+Q299Y+Y295F, A339S+G109A+Q345R+Q36 5S, A339S+G109A+Q345R+R320K, A339S+G109A+Q345R+R458K, A339S+G109A+Q345R+S323T, A339S+G109A+Q345R+V206L, A339S+G109A+Q345R+Y295F,<h2 style=";text-align:left;direction:ltr">A339S+G109A+Q365S+R320K, A339S+G109A+Q365S+R458K, A339S+G109A+Q365S+S323T, A339S+G109A+Q365S+V206L, A339S+G109A+Q365S+Y295F, A3 39S+G109A+R320K+R458K, A339S+G109A+R320K+S323T, A339S+G109A+R320K+V206L, A339S+G109A+R320K+Y295F, A339S+G109A+R458K+S323T, A339S +G109A+R458K+V206L、A339S+G109A+R458K+Y295F、A339S+G109A+S323T+V206L、A339S+G109A+S323T+Y295F、A339S+G109A+V206L+Y295F、A339S+G 149A+G182T+H1*, A339S+G149A+G182T+I9M, A339S+G149A+G182T+K391A, A339S+G149A+G182T+M202L, A339S+G149A+G182T+N16Y, A339S+G149A+G18 2T+N195F, A339S+G149A+G182T+N54S, A339S+G149A+G182T+Q169E, A339S+G149A+G182T+Q169E, A339S+G149A+G182T+Q172K, A339S+G149A+G182T+ Q299Y, A339S+G149A+G182T+Q345R, A339S+G149A+G182T+Q365S, A339S+G149A+G182T+R320K, A339S+G149A+G182T+R458K, A339S+G149A+G182T+S32 3T、A339S+G149A+G182T+V206L、A339S+G149A+G182T+Y295F、A339S+G149 A+H1*+I9M、A339S+G149A+H1*+K391A、A339S+G149A+H1*+M202L、A339S+G 149A+H1*+N16Y、A339S+G149A+H1*+N195F、A339S+G149A+H1*+N54S、A339S+G149A+H1*+Q169E、A339S+G149A+H1*+Q169E、A339S+G149A+H1*+Q172K、<h2 style=";text-align:left;direction:ltr">A339S+G149A+H1*+Q299Y、A339S+G149A+H1*+Q345R、A339S+G149A+H1*+Q365S、A339S+G149A+H1*+R320K、A339S+G149A+H1*+R458K、A339S+G149A+H1*+S323T、A339S+G149A+H1*+V206L、A339S+G149A+H1*+Y295F、A339S+G149A+I9M+K391A、A339、<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">S+G149A+I9M+M202L, A339S+G149A+I9M+N16Y, A339S+G149A+I9M+N195F, A339S+G149A+I9M+N54S, A339S+G149A+I9M+Q169E, A339S+G149A+I9M+Q169 E、A339S+G149A+I9M+Q172K、A339S+G149A+I9M+Q299Y、A339S+G149A+I9M+Q345R、A339S+G149A+I9M+Q365S、A339S+G149A+I9M+R320K、A339S+G149A+ I9M+R458K, A339S+G149A+I9M+S323T, A339S+G149A+I9M+V206L, A339S+G149A+I9M+Y295F, A339S+G149A+K391A+M202L, A339S+G149A+K391A+N16Y, A 339S+G149A+K391A+N195F、A339S+G149A+K391A+N54S、A339S+G149A+K391A+Q169E、A339S+G149A+K391A+Q169E、A339S+G149A+K391A+Q172K、A339S+ G149A+K391A+Q299Y, A339S+G149A+K391A+Q345R, A339S+G149A+K391A+Q365S, A339S+G149A+K391A+R320K, A339S+G149A+K391A+R458K, A339S+G149 A+K391A+S323T, A339S+G149A+K391A+V206L, A339S+G149A+K391A+Y295F, A339S+G149A+M202L+N16Y, A339S+G149A+M202L+N195F, A339S+G149A+M20 2L+N54S, A339S+G149A+M202L+Q169E, A339S+G149A+M202L+Q169E, A339S+G149A+M202L+Q172K, A339S+G149A+M202L+Q299Y, A339S+G149A+M202L+Q3 45R, A339S+G149A+M202L+Q365S, A339S+G149A+M202L+R320K, A339S+G149A+M202L+R458K, A339S+G149A+M202L+S323T, A339S+G149A+M202L+V206L,<h2 style=";text-align:left;direction:ltr">A339S+G149A+M202L+Y295F, A339S+G149A+N16Y+N195F, A339S+G149A+N16Y+N54S, A339S+G149A+N16Y+Q169E, A339S+G149A+N16Y+Q169E, A339S+G 149A+N16Y+Q172K, A339S+G149A+N16Y+Q299Y, A339S+G149A+N16Y+Q345R, A339S+G149A+N16Y+Q365S, A339S+G149A+N16Y+R320K, A339S+G149A+N16 Y+R458K, A339S+G149A+N16Y+S323T, A339S+G149A+N16Y+V206L, A339S+G149A+N16Y+Y295F, A339S+G149A+N195F+N54S, A339S+G149A+N195F+Q169E A339S+G149A+N195F+Q169E, A339S+G149A+N195F+Q172K, A339S+G149A+N195F+Q299Y, A339S+G149A+N195F+Q345R, A339S+G149A+N195F+Q365S, A3 39S+G149A+N195F+R320K, A339S+G149A+N195F+R458K, A339S+G149A+N195F+S323T, A339S+G149A+N195F+V206L, A339S+G149A+N195F+Y295F, A339 S+G149A+N54S+Q169E、A339S+G149A+N54S+Q169E、A339S+G149A+N54S+Q172K、A339S+G149A+N54S+Q299Y、A339S+G149A+N54S+Q345R、A339S+G149A+ N54S+Q365S, A339S+G149A+N54S+R320K, A339S+G149A+N54S+R458K, A339S+G149A+N54S+S323T, A339S+G149A+N54S+V206L, A339S+G149A+N54S+Y29 5F, A339S+G149A+Q169E+Q169E, A339S+G149A+Q169E+Q172K, A339S+G149A+Q169E+Q299Y, A339S+G149A+Q169E+Q345R, A339S+G149A+Q169E+Q365S,<h2 style=";text-align:left;direction:ltr">A339S+G149A+Q169E+R320K, A339S+G149A+Q169E+R458K, A339S+G149A+Q169E+S323T, A339S+G149A+Q169E+V206L, A339S+G149A+Q169E+Y295F, A33 9S+G149A+Q169E+Q172K、A339S+G149A+Q169E+Q299Y、A339S+G149A+Q169E+Q345R、A339S+G149A+Q169E+Q365S、A339S+G149A+Q169E+R320K、A339S+ G149A+Q169E+R458K, A339S+G149A+Q169E+S323T, A339S+G149A+Q169E+V206L, A339S+G149A+Q169E+Y295F, A339S+G149A+Q172K+Q299Y, A339S+G14 9A+Q172K+Q345R、A339S+G149A+Q172K+Q365S、A339S+G149A+Q172K+R320K、A339S+G149A+Q172K+R458K、A339S+G149A+Q172K+S323T、A339S+G149A+ Q172K+V206L, A339S+G149A+Q172K+Y295F, A339S+G149A+Q299Y+Q345R, A339S+G149A+Q299Y+Q365S, A339S+G149A+Q299Y+R320K, A339S+G149A+Q29 9Y+R458K, A339S+G149A+Q299Y+S323T, A339S+G149A+Q299Y+V206L, A339S+G149A+Q299Y+Y295F, A339S+G149A+Q345R+Q365S, A339S+G149A+Q345R+ R320K, A339S+G149A+Q345R+R458K, A339S+G149A+Q345R+S323T, A339S+G149A+Q345R+V206L, A339S+G149A+Q345R+Y295F, A339S+G149A+Q365S+R32 0K, A339S+G149A+Q365S+R458K, A339S+G149A+Q365S+S323T, A339S+G149A+Q365S+V206L, A339S+G149A+Q365S+Y295F, A339S+G149A+R320K+R458K,<h2 style=";text-align:left;direction:ltr">A339S+G149A+R320K+S323T, A339S+G149A+R320K+V206L, A339S+G149A+R320K+Y295F, A339S+G149A+R458K+S323T, A339S+G149A+R458K+V206L, A3 39S+G149A+R458K+Y295F、A339S+G149A+S323T+V206L、A339S+G149A+S323T+Y295F、A339S+G149A+V206L+Y295F、A339S+G182T+H1*+I9M、A339S+G18 2T+H1*+K391A、A339S+G182T+H1*+M202L、A339S+G182T+H1*+N16Y、A339S+G182T+H1*+N195F、A339S+G182T+H1*+N54S、A339S+G182T+H1*+Q169E、A3 39S+G182T+H1*+Q169E、A339S+G182T+H1*+Q172K、A339S+G182T+H1*+Q299Y、A339S+G182T+H1*+Q345R、A339S+G182T+H1*+Q365S、A339S+G182T+H1* +R320K、A339S+G182T+H1*+R458K、A339S+G182T+H1*+S323T、A339S+G182T+H1*+V206L、A339S+G182T+H1*+Y295F、A339S+G182T+I9M+K391A、A339S+ G182T+I9M+M202L, A339S+G182T+I9M+N16Y, A339S+G182T+I9M+N195F, A339S+G182T+I9M+N54S, A339S+G182T+I9M+Q169E, A339S+G182T+I9M+Q169E A339S+G182T+I9M+Q172K, A339S+G182T+I9M+Q299Y, A339S+G182T+I9M+Q345R, A339S+G182T+I9M+Q365S, A339S+G182T+I9M+R320K, A339S+G182T+ I9M+R458K, A339S+G182T+I9M+S323T, A339S+G182T+I9M+V206L, A339S+G182T+I9M+Y295F, A339S+G182T+K391A+M202L, A339S+G182T+K391A+N16Y,<h2 style=";text-align:left;direction:ltr">A339S+G182T+K391A+N195F, A339S+G182T+K391A+N54S, A339S+G182T+K391A+Q169E, A339S+G182T+K391A+Q169E, A339S+G182T+K391A+Q172K, A339 S+G182T+K391A+Q299Y、A339S+G182T+K391A+Q345R、A339S+G182T+K391A+ Q365S、A339S+G182T+K391A+R320K、A339S+G182T+K391A+R458K、A339S+G1 82T+K391A+S323T, A339S+G182T+K391A+V206L, A339S+G182T+K391A+Y295F, A339S+G182T+M202L+N16Y, A339S+G182T+M202L+N195F, A339S+G182T+M 202L+N54S, A339S+G182T+M202L+Q169E, A339S+G182T+M202L+Q169E, A339S+G182T+M202L+Q172K, A339S+G182T+M202L+Q299Y, A339S+G182T+M202L+ Q345R, A339S+G182T+M202L+Q365S, A339S+G182T+M202L+R320K, A339S+G182T+M202L+R458K, A339S+G182T+M202L+S323T, A339S+G182T+M202L+V20 6L、A339S+G182T+M202L+Y295F、A339S+G182T+N16Y+N195F、A339S+G182T+ N16Y+N54S、A339S+G182T+N16Y+Q169E、A339S+G182T+N16Y+Q169E、A339S+ G182T+N16Y+Q172K, A339S+G182T+N16Y+Q299Y, A339S+G182T+N16Y+Q345R, A339S+G182T+N16Y+Q365S, A339S+G182T+N16Y+R320K, A339S+G182T+N16 Y+R458K, A339S+G182T+N16Y+S323T, A339S+G182T+N16Y+V206L, A339S+G182T+N16Y+Y295F, A339S+G182T+N195F+N54S, A339S+G182T+N195F+Q169E,<h2 style=";text-align:left;direction:ltr">A339S+G182T+N195F+Q169E, A339S+G182T+N195F+Q172K, A339S+G182T+N195F+Q299Y, A339S+G182T+N195F+Q345R, A339S+G182T+N195F+Q365S, A339S+G182T+N195F+R320K, A339S+G182T+N195F+R458K, A339S+G182T+N195F+S323,<h2 style=";text-align:left;direction:ltr"> T、A339S+G182T+N195F+V206L、A339S+G182T+N195F+Y295F、A339S+G182T+N54S+Q169E、A339S+G182T+N54S+Q169E、A339S+G182T+N54S+Q172K、A339S+G182T+N54S+Q299Y、A339S+G182T+N54S+Q345R、A339S+G182T+N54S+Q365S、A339S+G182T+N54S+R320K、A339S+G182T+N54S+R458K、A339S+G182T+N54S+S323T、A339S+G182T+N54S+V206L、A339S+G182T+N54S+Y295F、A339S+G182T+Q169E+Q169E、A339S+G182T+Q169E+Q172K、A339S+G182T+Q169E+Q299Y、A339S+G182T+Q169E+Q345R、A339S+G182T+Q169E+Q365S、A339S+G182T+Q169E+R320K、A339S+G182T+Q169E+R458K、A339S+G182T+Q169E+S323T、A339S+G182T+Q169E+V206L、A339S+G182T+Q169E+Y295F、A339S+G182T+Q169E+Q172K、A339S+G182T+Q169E+Q299Y、A339S+G182T+Q169E+Q345R、A339S+G182T+Q169E+Q365S、A339S+G182T+Q169E+R320K、A339S+G182T+Q169E+R458K、A339S+G182T+Q169E+S323T、A339S+G182T+Q169E+V206L、A339S+G182T+Q169E+Y295F、A339S+G182T+Q172K+Q299Y、A339S+G182T+Q172K+Q345R、A339S+G182T+Q172K+Q365S、A339S+G182T+Q172K+R320K、A339S+G182T+Q172K+R458K、A339S+G182T+Q172K+S323T、A339S+G182T+Q172K+V206L、A339S+G182T+Q172K+Y295F、A339S+G182T+Q299Y+Q345R、A339S+G182T+Q299Y+Q365S、<h2 style=";text-align:left;direction:ltr">A339S+G182T+Q299Y+R320K, A339S+G182T+Q299Y+R458K, A339S+G182T+Q299Y+S323T, A339S+G182T+Q299Y+V206L, A339S+G182T+Q299Y+Y295F, A33 9S+G182T+Q345R+Q365S、A339S+G182T+Q345R+R320K、A339S+G182T+Q345R+R458K、A339S+G182T+Q345R+S323T、A339S+G182T+Q345R+V206L、A339S+ G182T+Q345R+Y295F, A339S+G182T+Q365S+R320K, A339S+G182T+Q365S+R458K, A339S+G182T+Q365S+S323T, A339S+G182T+Q365S+V206L, A339S+G18 2T+Q365S+Y295F、A339S+G182T+R320K+R458K、A339S+G182T+R320K+S323T、A339S+G182T+R320K+V206L、A339S+G182T+R320K+Y295F、A339S+G182T+ R458K+S323T, A339S+G182T+R458K+V206L, A339S+G182T+R458K+Y295F, A339S+G182T+S323T+V206L, A339S+G182T+S323T+Y295F, A339S+G182T+V20 6L+Y295F、A339S+H1*+I9M+K391A、A339S+H1*+I9M+M202L、A339S+H1*+I9 M+N16Y、A339S+H1*+I9M+N195F、A339S+H1*+I9M+N54S、A339S+H1*+I9M+Q1 69E, A339S+H1*+I9M+Q169E, A339S+H1*+I9M+Q172K, A339S+H1*+I9M+Q299Y, A339S+H1*+I9M+Q345R, A339S+H1*+I9M+Q365S, A339S+H1*+I9M+R320K A339S+H1*+I9M+R458K, A339S+H1*+I9M+S323T, A339S+H1*+I9M+V206L, A339S+H1*+I9M+Y295F, A339S+H1*+K391A+M202L, A339S+H1*+K391A+N16Y<h2 style=";text-align:left;direction:ltr">A339S+H1*+K391A+N195F、A339S+H1*+K391A+N54S、A339S+H1*+K391A+Q169E、A339S+H1*+K391A+Q169E、A339S+H1*+K391A+Q172K、A339S+H1*+K391A +Q299Y、A339S+H1*+K391A+Q345R、A339S+H1*+K391A+Q365S、A339S+H1*+K391A+R320K、A339S+H1*+K391A+R458K、A339S+H1*+K391A+S323T、A339S+H 1*+K391A+V206L、A339S+H1*+K391A+Y295F、A339S+H1*+M202L+N16Y、A339S+H1*+M202L+N195F、A339S+H1*+M202L+N54S、A339S+H1*+M202L+Q169E、A 339S+H1*+M202L+Q169E、A339S+H1*+M202L+Q172K、A339S+H1*+M202L+Q299Y、A339S+H1*+M202L+Q345R、A339S+H1*+M202L+Q365S、A339S+H1*+M202L+ R320K, A339S+H1*+M202L+R458K, A339S+H1*+M202L+S323T, A339S+H1*+M202L+V206L, A339S+H1*+M202L+Y295F, A339S+H1*+N16Y+N195F, A339S+H1* +N16Y+N54S、A339S+H1*+N16Y+Q169E、A339S+H1*+N16Y+Q169E、A339S+H1*+N16Y+Q172K、A339S+H1*+N16Y+Q299Y、A339S+H1*+N16Y+Q345R、A339S+H1 *+N16Y+Q365S、A339S+H1*+N16Y+R320K、A339S+H1*+N16Y+R458K、A339S+H1*+N16Y+S323T、A339S+H1*+N16Y+V206L、A339S+H1*+N16Y+Y295F、A339S+ H1*+N195F+N54S、A339S+H1*+N195F+Q169E、A339S+H1*+N195F+Q169E、A339S+H1*+N195F+Q172K、A339S+H1*+N195F+Q299Y、A339S+H1*+N195F+Q345R、<h2 style=";text-align:left;direction:ltr">A339S+H1*+N195F+Q365S、A339S+H1*+N195F+R320K、A339S+H1*+N195F+R458K、A339S+H1*+N195F+S323T、A339S+H1*+N195F+V206L、A339S+H1*+N195F +Y295F、A339S+H1*+N54S+Q169E、A339S+H1*+N54S+Q169E、A339S+H1*+N54S+Q172K、A339S+H1*+N54S+Q299Y、A339S+H1*+N54S+Q345R、A339S+H1*+N54 S+Q365S、A339S+H1*+N54S+R320K、A339S+H1*+N54S+R458K、A339S+H1*+N5 4S+S323T、A339S+H1*+N54S+V206L、A339S+H1*+N54S+Y295F、A339S+H1*+Q1 69E+Q169E, A339S+H1*+Q169E+Q172K, A339S+H1*+Q169E+Q299Y, A339S+H1*+Q169E+Q345R, A339S+H1*+Q169E+Q365S, A339S+H1*+Q169E+R320K, A339S +H1*+Q169E+R458K、A339S+H1*+Q169E+S323T、A339S+H1*+Q169E+V206L、A339S+H1*+Q169E+Y295F、A339S+H1*+Q169E+Q172K、A339S+H1*+Q169E+Q299 Y、A339S+H1*+Q169E+Q345R、A339S+H1*+Q169E+Q365S、A339S+H1*+Q169E+R320K、A339S+H1*+Q169E+R458K、A339S+H1*+Q169E+S323T、A339S+H1*+Q16 9E+V206L、A339S+H1*+Q169E+Y295F、A339S+H1*+Q172K+Q299Y、A339S+H1* +Q172K+Q345R、A339S+H1*+Q172K+Q365S、A339S+H1*+Q172K+R320K、A339S+ H1*+Q172K+R458K, A339S+H1*+Q172K+S323T, A339S+H1*+Q172K+V206L, A339S+H1*+Q172K+Y295F, A339S+H1*+Q299Y+Q345R, A339S+H1*+Q299Y+Q365S,<h2 style=";text-align:left;direction:ltr">A339S+H1*+Q299Y+R320K, A339S+H1*+Q299Y+R458K, A339S+H1*+Q299Y+S323T, A339S+H1*+Q299Y+V206L, A339S+H1*+Q299Y+Y295F, A339S+H1*+Q34 5R+Q365S, A339S+H1*+Q345R+R320K, A339S+H1*+Q345R+R458K, A339S+H1*+Q345R+S323T, A339S+H1*+Q345R+V206L, A339S+H1*+Q345R+Y295F, A339 S+H1*+Q365S+R320K、A339S+H1*+Q365S+R458K、A339S+H1*+Q365S+S323T 、A339S+H1*+Q365S+V206L、A339S+H1*+Q365S+Y295F、A339S+H1*+R320K+R 458K, A339S+H1*+R320K+S323T, A339S+H1*+R320K+V206L, A339S+H1*+R320K+Y295F, A339S+H1*+R458K+S323T, A339S+H1*+R458K+V206L, A339S+H1* +R458K+Y295F、A339S+H1*+S323T+V206L、A339S+H1*+S323T+Y295F、A339S+H1*+V206L+Y295F、A339S+I9M+K391A+M202L、A339S+I9M+K391A+N16Y、A 339S+I9M+K391A+N195F, A339S+I9M+K391A+N54S, A339S+I9M+K391A+Q169E, A339S+I9M+K391A+Q169E, A339S+I9M+K391A+Q172K, A339S+I9M+K391A +Q299Y、A339S+I9M+K391A+Q345R、A339S+I9M+K391A+Q365S、A339S+I9M+K391A+R320K、A339S+I9M+K391A+R458K、A339S+I9M+K391A+S323T、A339S+ I9M+K391A+V206L, A339S+I9M+K391A+Y295F, A339S+I9M+M202L+N16Y, A339S+I9M+M202L+N195F, A339S+I9M+M202L+N54S, A339S+I9M+M202L+Q169E,<h2 style=";text-align:left;direction:ltr">A339S+I9M+M202L+Q169E, A339S+I9M+M202L+Q172K, A339S+I9M+M202L+Q299Y, A339S+I9M+M202L+Q345R, A339S+I9M+M202L+Q365S, A339S+I9M+M202L+R320K, A339S+I9M+M202L+R458K, A3,<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">39S+I9M+M202L+S323T, A339S+I9M+M202L+V206L, A339S+I9M+M202L+Y295F, A339S+I9M+N16Y+N195F, A339S+I9M+N16Y+N54S, A339S+I9M+N16Y+Q16 9E、A339S+I9M+N16Y+Q169E、A339S+I9M+N16Y+Q172K、A339S+I9M+N16Y+Q 299Y、A339S+I9M+N16Y+Q345R、A339S+I9M+N16Y+Q365S、A339S+I9M+N16Y+ R320K, A339S+I9M+N16Y+R458K, A339S+I9M+N16Y+S323T, A339S+I9M+N16Y+V206L, A339S+I9M+N16Y+Y295F, A339S+I9M+N195F+N54S, A339S+I9M+N1 95F+Q169E, A339S+I9M+N195F+Q169E, A339S+I9M+N195F+Q172K, A339S+I9M+N195F+Q299Y, A339S+I9M+N195F+Q345R, A339S+I9M+N195F+Q365S, A33 9S+I9M+N195F+R320K, A339S+I9M+N195F+R458K, A339S+I9M+N195F+S323T, A339S+I9M+N195F+V206L, A339S+I9M+N195F+Y295F, A339S+I9M+N54S+Q 169E, A339S+I9M+N54S+Q169E, A339S+I9M+N54S+Q172K, A339S+I9M+N54S+Q299Y, A339S+I9M+N54S+Q345R, A339S+I9M+N54S+Q365S, A339S+I9M+N54 S+R320K, A339S+I9M+N54S+R458K, A339S+I9M+N54S+S323T, A339S+I9M+N54S+V206L, A339S+I9M+N54S+Y295F, A339S+I9M+Q169E+Q169E, A339S+I9M +Q169E+Q172K, A339S+I9M+Q169E+Q299Y, A339S+I9M+Q169E+Q345R, A339S+I9M+Q169E+Q365S, A339S+I9M+Q169E+R320K, A339S+I9M+Q169E+R458K,<h2 style=";text-align:left;direction:ltr">A339S+I9M+Q169E+S323T, A339S+I9M+Q169E+V206L, A339S+I9M+Q169E+Y295F, A339S+I9M+Q169E+Q172K, A339S+I9M+Q169E+Q299Y, A339S+I9M+Q16 9E+Q345R、A339S+I9M+Q169E+Q365S、A339S+I9M+Q169E+R320K、A339S+I9M +Q169E+R458K、A339S+I9M+Q169E+S323T、A339S+I9M+Q169E+V206L、A339S +I9M+Q169E+Y295F, A339S+I9M+Q172K+Q299Y, A339S+I9M+Q172K+Q345R, A339S+I9M+Q172K+Q365S, A339S+I9M+Q172K+R320K, A339S+I9M+Q172K+R45 8K, A339S+I9M+Q172K+S323T, A339S+I9M+Q172K+V206L, A339S+I9M+Q172K+Y295F, A339S+I9M+Q299Y+Q345R, A339S+I9M+Q299Y+Q365S, A339S+I9M+Q 299Y+R320K, A339S+I9M+Q299Y+R458K, A339S+I9M+Q299Y+S323T, A339S+I9M+Q299Y+V206L, A339S+I9M+Q299Y+Y295F, A339S+I9M+Q345R+Q365S, A3 39S+I9M+Q345R+R320K, A339S+I9M+Q345R+R458K, A339S+I9M+Q345R+S323T, A339S+I9M+Q345R+V206L, A339S+I9M+Q345R+Y295F, A339S+I9M+Q365S+ R320K, A339S+I9M+Q365S+R458K, A339S+I9M+Q365S+S323T, A339S+I9M+Q365S+V206L, A339S+I9M+Q365S+Y295F, A339S+I9M+R320K+R458K, A339S+I9 M+R320K+S323T, A339S+I9M+R320K+V206L, A339S+I9M+R320K+Y295F, A339S+I9M+R458K+S323T, A339S+I9M+R458K+V206L, A339S+I9M+R458K+Y295F,<h2 style=";text-align:left;direction:ltr">A339S+I9M+S323T+V206L, A339S+I9M+S323T+Y295F, A339S+I9M+V206L+Y295F, A339S+K391A+M202L+N16Y, A339S+K391A+M202L+N195F, A339S+K391 A+M202L+N54S, A339S+K391A+M202L+Q169E, A339S+K391A+M202L+Q169E, A339S+K391A+M202L+Q172K, A339S+K391A+M202L+Q299Y, A339S+K391A+M2 02L+Q345R, A339S+K391A+M202L+Q365S, A339S+K391A+M202L+R320K, A339S+K391A+M202L+R458K, A339S+K391A+M202L+S323T, A339S+K391A+M202L +V206L、A339S+K391A+M202L+Y295F、A339S+K391A+N16Y+N195F、A339S+K391A+N16Y+N54S、A339S+K391A+N16Y+Q169E、A339S+K391A+N16Y+Q169E、A 339S+K391A+N16Y+Q172K, A339S+K391A+N16Y+Q299Y, A339S+K391A+N16Y+Q345R, A339S+K391A+N16Y+Q365S, A339S+K391A+N16Y+R320K, A339S+K39 1A+N16Y+R458K, A339S+K391A+N16Y+S323T, A339S+K391A+N16Y+V206L, A339S+K391A+N16Y+Y295F, A339S+K391A+N195F+N54S, A339S+K391A+N195F +Q169E、A339S+K391A+N195F+Q169E、A339S+K391A+N195F+Q172K、A339S+K391A+N195F+Q299Y、A339S+K391A+N195F+Q345R、A339S+K391A+N195F+Q3 65S, A339S+K391A+N195F+R320K, A339S+K391A+N195F+R458K, A339S+K391A+N195F+S323T, A339S+K391A+N195F+V206L, A339S+K391A+N195F+Y295F,<h2 style=";text-align:left;direction:ltr">A339S+K391A+N54S+Q169E, A339S+K391A+N54S+Q169E, A339S+K391A+N54S+Q172K, A339S+K391A+N54S+Q299Y, A339S+K391A+N54S+Q345R, A339S+K39 1A+N54S+Q365S、A339S+K391A+N54S+R320K、A339S+K391A+N54S+R458K、A339S+K391A+N54S+S323T、A339S+K391A+N54S+V206L、A339S+K391A+N54S+Y2 95F, A339S+K391A+Q169E+Q169E, A339S+K391A+Q169E+Q172K, A339S+K391A+Q169E+Q299Y, A339S+K391A+Q169E+Q345R, A339S+K391A+Q169E+Q365S, A339S+K391A+Q169E+R320K, A339S+K391A+Q169E+R458K, A339S+K391A+Q169E+S323T, A339S+K391A+Q169E+V206L, A339S+K391A+Q169E+Y295F, A339S +K391A+Q169E+Q172K, A339S+K391A+Q169E+Q299Y, A339S+K391A+Q169E+Q345R, A339S+K391A+Q169E+Q365S, A339S+K391A+Q169E+R320K, A339S+K39 1A+Q169E+R458K, A339S+K391A+Q169E+S323T, A339S+K391A+Q169E+V206L, A339S+K391A+Q169E+Y295F, A339S+K391A+Q172K+Q299Y, A339S+K391A+Q1 72K+Q345R, A339S+K391A+Q172K+Q365S, A339S+K391A+Q172K+R320K, A339S+K391A+Q172K+R458K, A339S+K391A+Q172K+S323T, A339S+K391A+Q172K+V 206L, A339S+K391A+Q172K+Y295F, A339S+K391A+Q299Y+Q345R, A339S+K391A+Q299Y+Q365S, A339S+K391A+Q299Y+R320K, A339S+K391A+Q299Y+R458K,<h2 style=";text-align:left;direction:ltr">A339S+K391A+Q299Y+S323T, A339S+K391A+Q299Y+V206L, A339S+K391A+Q299Y+Y295F, A339S+K391A+Q345R+Q365S, A339S+K391A+Q345R+R320K, A339 S+K391A+Q345R+R458K, A339S+K391A+Q345R+S323T, A339S+K391A+Q345R+V206L, A339S+K391A+Q345R+Y295F, A339S+K391A+Q365S+R320K, A339S+K3 91A+Q365S+R458K, A339S+K391A+Q365S+S323T, A339S+K391A+Q365S+V206L, A339S+K391A+Q365S+Y295F, A339S+K391A+R320K+R458K, A339S+K391A+ R320K+S323T, A339S+K391A+R320K+V206L, A339S+K391A+R320K+Y295F, A339S+K391A+R458K+S323T, A339S+K391A+R458K+V206L, A339S+K391A+R458 K+Y295F, A339S+K391A+S323T+V206L, A339S+K391A+S323T+Y295F, A339S+K391A+V206L+Y295F, A339S+M202L+N16Y+N195F, A339S+M202L+N16Y+N54S A339S+M202L+N16Y+Q169E, A339S+M202L+N16Y+Q169E, A339S+M202L+N16Y+Q172K, A339S+M202L+N16Y+Q299Y, A339S+M202L+N16Y+Q345R, A339S+M2 02L+N16Y+Q365S、A339S+M202L+N16Y+R320K、A339S+M202L+N16Y+R458K、A339S+M202L+N16Y+S323T、A339S+M202L+N16Y+V206L、A339S+M202L+N16Y+ Y295F, A339S+M202L+N195F+N54S, A339S+M202L+N195F+Q169E, A339S+M202L+N195F+Q169E, A339S+M202L+N195F+Q172K, A339S+M202L+N195F+Q299Y,<h2 style=";text-align:left;direction:ltr">A339S+M202L+N195F+Q345R, A339S+M202L+N195F+Q365S, A339S+M202L+N195F+R320K, A339S+M202L+N195F+R458K, A339S+M202L+N195F+S323T, A339S+M202L+N195F+V206L, A339S+M202L+N195F+Y295F, A339<h2 style=";text-align:left;direction:ltr"> 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style=";text-align:left;direction:ltr">A339S+M202L+Q299Y+S323T, A339S+M202L+Q299Y+V206L, A339S+M202L+Q299Y+Y295F, A339S+M202L+Q345R+Q365S, A339S+M202L+Q345R+R320K, A3 39S+M202L+Q345R+R458K, A339S+M202L+Q345R+S323T, A339S+M202L+Q345R+V206L, A339S+M202L+Q345R+Y295F, A339S+M202L+Q365S+R320K, A339S +M202L+Q365S+R458K, A339S+M202L+Q365S+S323T, A339S+M202L+Q365S+V206L, A339S+M202L+Q365S+Y295F, A339S+M202L+R320K+R458K, A339S+M2 02L+R320K+S323T, A339S+M202L+R320K+V206L, A339S+M202L+R320K+Y295F, A339S+M202L+R458K+S323T, A339S+M202L+R458K+V206L, A339S+M202L +R458K+Y295F、A339S+M202L+S323T+V206L、A339S+M202L+S323T+Y295F、A339S+M202L+V206L+Y295F、A339S+N16Y+N195F+N54S、A339S+N16Y+N195F +Q169E、A339S+N16Y+N195F+Q169E、A339S+N16Y+N195F+Q172K、A339S+N1 6Y+N195F+Q299Y、A339S+N16Y+N195F+Q345R、A339S+N16Y+N195F+Q365S、A 339S+N16Y+N195F+R320K, A339S+N16Y+N195F+R458K, A339S+N16Y+N195F+S323T, A339S+N16Y+N195F+V206L, A339S+N16Y+N195F+Y295F, A339S+N16 Y+N54S+Q169E、A339S+N16Y+N54S+Q169E、A339S+N16Y+N54S+Q172K、A339S+N16Y+N54S+Q299Y、A339S+N16Y+N54S+Q345R、A339S+N16Y+N54S+Q365S、<h2 style=";text-align:left;direction:ltr">A339S+N16Y+N54S+R320K, A339S+N16Y+N54S+R458K, A339S+N16Y+N54S+S323T, A339S+N16Y+N54S+V206L, A339S+N16Y+N54S+Y295F, A339S+N16Y+Q1 69E+Q169E, A339S+N16Y+Q169E+Q172K, A339S+N16Y+Q169E+Q299Y, A339S+N16Y+Q169E+Q345R, A339S+N16Y+Q169E+Q365S, A339S+N16Y+Q169E+R320 K、A339S+N16Y+Q169E+R458K、A339S+N16Y+Q169E+S323T、A339S+N16Y+Q1 69E+V206L、A339S+N16Y+Q169E+Y295F、A339S+N16Y+Q169E+Q172K、A339S+ N16Y+Q169E+Q299Y, A339S+N16Y+Q169E+Q345R, A339S+N16Y+Q169E+Q365S, A339S+N16Y+Q169E+R320K, A339S+N16Y+Q169E+R458K, A339S+N16Y+Q16 9E+S323T、A339S+N16Y+Q169E+V206L、A339S+N16Y+Q169E+Y295F、A339S+ N16Y+Q172K+Q299Y、A339S+N16Y+Q172K+Q345R、A339S+N16Y+Q172K+Q365S A339S+N16Y+Q172K+R320K, A339S+N16Y+Q172K+R458K, A339S+N16Y+Q172K+S323T, A339S+N16Y+Q172K+V206L, A339S+N16Y+Q172K+Y295F, A339S+N 16Y+Q299Y+Q345R, A339S+N16Y+Q299Y+Q365S, A339S+N16Y+Q299Y+R320K, A339S+N16Y+Q299Y+R458K, A339S+N16Y+Q299Y+S323T, A339S+N16Y+Q299 Y+V206L、A339S+N16Y+Q299Y+Y295F、A339S+N16Y+Q345R+Q365S、A339S+N16Y+Q345R+R320K、A339S+N16Y+Q345R+R458K、A339S+N16Y+Q345R+S323T、<h2 style=";text-align:left;direction:ltr">A339S+N16Y+Q345R+V206L, A339S+N16Y+Q345R+Y295F, A339S+N16Y+Q365S+R320K, A339S+N16Y+Q365S+R458K, A339S+N16Y+Q365S+S323T, A339S+N 16Y+Q365S+V206L, A339S+N16Y+Q365S+Y295F, A339S+N16Y+R320K+R458K, A339S+N16Y+R320K+S323T, A339S+N16Y+R320K+V206L, A339S+N16Y+R320 K+Y295F、A339S+N16Y+R458K+S323T、A339S+N16Y+R458K+V206L、A339S+N 16Y+R458K+Y295F、A339S+N16Y+S323T+V206L、A339S+N16Y+S323T+Y295F A339S+N16Y+V206L+Y295F, A339S+N195F+N54S+Q169E, A339S+N195F+N54S+Q169E, A339S+N195F+N54S+Q172K, A339S+N195F+N54S+Q299Y, A339S+N 195F+N54S+Q345R, A339S+N195F+N54S+Q365S, A339S+N195F+N54S+R320K, A339S+N195F+N54S+R458K, A339S+N195F+N54S+S323T, A339S+N195F+N5 4S+V206L、A339S+N195F+N54S+Y295F、A339S+N195F+Q169E+Q169E、A339S +N195F+Q169E+Q172K、A339S+N195F+Q169E+Q299Y、A339S+N195F+Q169E+Q 345R, A339S+N195F+Q169E+Q365S, A339S+N195F+Q169E+R320K, A339S+N195F+Q169E+R458K, A339S+N195F+Q169E+S323T, A339S+N195F+Q169E+V20 6L、A339S+N195F+Q169E+Y295F、A339S+N195F+Q169E+Q172K、A339S+N195 F+Q169E+Q299Y、A339S+N195F+Q169E+Q345R、A339S+N195F+Q169E+Q365S、<h2 style=";text-align:left;direction:ltr">A339S+N195F+Q169E+R320K, A339S+N195F+Q169E+R458K, A339S+N195F+Q169E+S323T, A339S+N195F+Q169E+V206L, A339S+N195F+Q169E+Y295F, A33 9S+N195F+Q172K+Q299Y、A339S+N195F+Q172K+Q345R、A339S+N195F+Q172K+Q365S、A339S+N195F+Q172K+R320K、A339S+N195F+Q172K+R458K、A339S+ N195F+Q172K+S323T, A339S+N195F+Q172K+V206L, A339S+N195F+Q172K+Y295F, A339S+N195F+Q299Y+Q345R, A339S+N195F+Q299Y+Q365S, A339S+N19 5F+Q299Y+R320K, A339S+N195F+Q299Y+R458K, A339S+N195F+Q299Y+S323T, A339S+N195F+Q299Y+V206L, A339S+N195F+Q299Y+Y295F, A339S+N195F+ Q345R+Q365S, A339S+N195F+Q345R+R320K, A339S+N195F+Q345R+R458K, A339S+N195F+Q345R+S323T, A339S+N195F+Q345R+V206L, A339S+N195F+Q34 5R+Y295F、A339S+N195F+Q365S+R320K、A339S+N195F+Q365S+R458K、A339S+N195F+Q365S+S323T、A339S+N195F+Q365S+V206L、A339S+N195F+Q365S+ Y295F, A339S+N195F+R320K+R458K, A339S+N195F+R320K+S323T, A339S+N195F+R320K+V206L, A339S+N195F+R320K+Y295F, A339S+N195F+R458K+S32 3T、A339S+N195F+R458K+V206L、A339S+N195F+R458K+Y295F、A339S+N195 F+S323T+V206L、A339S+N195F+S323T+Y295F、A339S+N195F+V206L+Y295F、<h2 style=";text-align:left;direction:ltr">A339S+N54S+Q169E+Q169E, A339S+N54S+Q169E+Q172K, A339S+N54S+Q169E+Q299Y, A339S+N54S+Q169E+Q345R, A339S+N54S+Q169E+Q365S, A339S+N54S+Q169E+R320K, A339S+N54S+Q169E+R458K, A339S+N54S+Q169E+S323T, A339S+N54S+Q1,<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">69E+V206L, A339S+N54S+Q169E+Y295F, A339S+N54S+Q169E+Q172K, A339S+N54S+Q169E+Q299Y, A339S+N54S+Q169E+Q345R, A339S+N54S+Q169E+Q365S A339S+N54S+Q169E+R320K, A339S+N54S+Q169E+R458K, A339S+N54S+Q169E+S323T, A339S+N54S+Q169E+V206L, A339S+N54S+Q169E+Y295F, A339S+N54 S+Q172K+Q299Y, A339S+N54S+Q172K+Q345R, A339S+N54S+Q172K+Q365S, A339S+N54S+Q172K+R320K, A339S+N54S+Q172K+R458K, A339S+N54S+Q172K+S3 23T, A339S+N54S+Q172K+V206L, A339S+N54S+Q172K+Y295F, A339S+N54S+Q299Y+Q345R, A339S+N54S+Q299Y+Q365S, A339S+N54S+Q299Y+R320K, A339S+ N54S+Q299Y+R458K, A339S+N54S+Q299Y+S323T, A339S+N54S+Q299Y+V206L, A339S+N54S+Q299Y+Y295F, A339S+N54S+Q345R+Q365S, A339S+N54S+Q345R +R320K, A339S+N54S+Q345R+R458K, A339S+N54S+Q345R+S323T, A339S+N54S+Q345R+V206L, A339S+N54S+Q345R+Y295F, A339S+N54S+Q365S+R320K, A33 9S+N54S+Q365S+R458K、A339S+N54S+Q365S+S323T、A339S+N54S+Q365S+V206L、A339S+N54S+Q365S+Y295F、A339S+N54S+R320K+R458K、A339S+N54S+R3 20K+S323T, A339S+N54S+R320K+V206L, A339S+N54S+R320K+Y295F, A339S+N54S+R458K+S323T, A339S+N54S+R458K+V206L, A339S+N54S+R458K+Y295F,<h2 style=";text-align:left;direction:ltr">A339S+N54S+S323T+V206L, A339S+N54S+S323T+Y295F, A339S+N54S+V206L+Y295F, A339S+Q169E+Q169E+Q172K, A339S+Q169E+Q169E+Q299Y, A339S +Q169E+Q169E+Q345R, A339S+Q169E+Q169E+Q365S, A339S+Q169E+Q169E+R320K, A339S+Q169E+Q169E+R458K, A339S+Q169E+Q169E+S323T, A339S+Q1 69E+Q169E+V206L, A339S+Q169E+Q169E+Y295F, A339S+Q169E+Q172K+Q299Y, A339S+Q169E+Q172K+Q345R, A339S+Q169E+Q172K+Q365S, A339S+Q169 E+Q172K+R320K, A339S+Q169E+Q172K+R458K, A339S+Q169E+Q172K+S323T, A339S+Q169E+Q172K+V206L, A339S+Q169E+Q172K+Y295F, A339S+Q169E+Q 299Y+Q345R, A339S+Q169E+Q299Y+Q365S, A339S+Q169E+Q299Y+R320K, A339S+Q169E+Q299Y+R458K, A339S+Q169E+Q299Y+S323T, A339S+Q169E+Q29 9Y+V206L、A339S+Q169E+Q299Y+Y295F、A339S+Q169E+Q345R+Q365S、A339S+Q169E+Q345R+R320K、A339S+Q169E+Q345R+R458K、A339S+Q169E+Q345R+ S323T, A339S+Q169E+Q345R+V206L, A339S+Q169E+Q345R+Y295F, A339S+Q169E+Q365S+R320K, A339S+Q169E+Q365S+R458K, A339S+Q169E+Q365S+S32 3T、A339S+Q169E+Q365S+V206L、A339S+Q169E+Q365S+Y295F、A339S+Q169 E+R320K+R458K、A339S+Q169E+R320K+S323T、A339S+Q169E+R320K+V206L、<h2 style=";text-align:left;direction:ltr">A339S+Q169E+R320K+Y295F, A339S+Q169E+R458K+S323T, A339S+Q169E+R458K+V206L, A339S+Q169E+R458K+Y295F, A339S+Q169E+S323T+V206L, A33 9S+Q169E+S323T+Y295F、A339S+Q169E+V206L+Y295F、A339S+Q169E+Q172K+Q299Y、A339S+Q169E+Q172K+Q345R、A339S+Q169E+Q172K+Q365S、A339S+ Q169E+Q172K+R320K, A339S+Q169E+Q172K+R458K, A339S+Q169E+Q172K+S323T, A339S+Q169E+Q172K+V206L, A339S+Q169E+Q172K+Y295F, A339S+Q16 9E+Q299Y+Q345R、A339S+Q169E+Q299Y+Q365S、A339S+Q169E+Q299Y+R320 K、A339S+Q169E+Q299Y+R458K、A339S+Q169E+Q299Y+S323T、A339S+Q169E+ Q299Y+V206L, A339S+Q169E+Q299Y+Y295F, A339S+Q169E+Q345R+Q365S, A339S+Q169E+Q345R+R320K, A339S+Q169E+Q345R+R458K, A339S+Q169E+Q34 5R+S323T, A339S+Q169E+Q345R+V206L, A339S+Q169E+Q345R+Y295F, A339S+Q169E+Q365S+R320K, A339S+Q169E+Q365S+R458K, A339S+Q169E+Q365S+ S323T, A339S+Q169E+Q365S+V206L, A339S+Q169E+Q365S+Y295F, A339S+Q169E+R320K+R458K, A339S+Q169E+R320K+S323T, A339S+Q169E+R320K+V20 6L、A339S+Q169E+R320K+Y295F、A339S+Q169E+R458K+S323T、A339S+Q169 E+R458K+V206L、A339S+Q169E+R458K+Y295F、A339S+Q169E+S323T+V206L、<h2 style=";text-align:left;direction:ltr">A339S+Q169E+S323T+Y295F, A339S+Q169E+V206L+Y295F, A339S+Q172K+Q299Y+Q345R, A339S+Q172K+Q299Y+Q365S, A339S+Q172K+Q299Y+R320K, A33 9S+Q172K+Q299Y+R458K、A339S+Q172K+Q299Y+S323T、A339S+Q172K+Q299Y+V206L、A339S+Q172K+Q299Y+Y295F、A339S+Q172K+Q345R+Q365S、A339S+ Q172K+Q345R+R320K, A339S+Q172K+Q345R+R458K, A339S+Q172K+Q345R+S323T, A339S+Q172K+Q345R+V206L, A339S+Q172K+Q345R+Y295F, A339S+Q17 2K+Q365S+R320K, A339S+Q172K+Q365S+R458K, A339S+Q172K+Q365S+S323T, A339S+Q172K+Q365S+V206L, A339S+Q172K+Q365S+Y295F, A339S+Q172K+ R320K+R458K, A339S+Q172K+R320K+S323T, A339S+Q172K+R320K+V206L, A339S+Q172K+R320K+Y295F, A339S+Q172K+R458K+S323T, A339S+Q172K+R45 8K+V206L, A339S+Q172K+R458K+Y295F, A339S+Q172K+S323T+V206L, A339S+Q172K+S323T+Y295F, A339S+Q172K+V206L+Y295F, A339S+Q299Y+Q345R+ Q365S, A339S+Q299Y+Q345R+R320K, A339S+Q299Y+Q345R+R458K, A339S+Q299Y+Q345R+S323T, A339S+Q299Y+Q345R+V206L, A339S+Q299Y+Q345R+Y29 5F、A339S+Q299Y+Q365S+R320K、A339S+Q299Y+Q365S+R458K、A339S+Q299Y+Q365S+S323T、A339S+Q299Y+Q365S+V206L、A339S+Q299Y+Q365S+Y295F、<h2 style=";text-align:left;direction:ltr">A339S+Q299Y+R320K+R458K, A339S+Q299Y+R320K+S323T, A339S+Q299Y+R320K+V206L, A339S+Q299Y+R320K+Y295F, A339S+Q299Y+R458K+S323T, A33 9S+Q299Y+R458K+V206L、A339S+Q299Y+R458K+Y295F、A339S+Q299Y+S323T+V206L、A339S+Q299Y+S323T+Y295F、A339S+Q299Y+V206L+Y295F、A339S+ Q345R+Q365S+R320K, A339S+Q345R+Q365S+R458K, A339S+Q345R+Q365S+S323T, A339S+Q345R+Q365S+V206L, A339S+Q345R+Q365S+Y295F, A339S+Q34 5R+R320K+R458K、A339S+Q345R+R320K+S323T、A339S+Q345R+R320K+V206L、A339S+Q345R+R320K+Y295F、A339S+Q345R+R458K+S323T、A339S+Q345R+ R458K+V206L, A339S+Q345R+R458K+Y295F, A339S+Q345R+S323T+V206L, A339S+Q345R+S323T+Y295F, A339S+Q345R+V206L+Y295F, A339S+Q365S+R32 0K+R458K、A339S+Q365S+R320K+S323T、A339S+Q365S+R320K+V206L、A339S+Q365S+R320K+Y295F、A339S+Q365S+R458K+S323T、A339S+Q365S+R458K+ V206L, A339S+Q365S+R458K+Y295F, A339S+Q365S+S323T+V206L, A339S+Q365S+S323T+Y295F, A339S+Q365S+V206L+Y295F, A339S+R320K+R458K+S32 3T、A339S+R320K+R458K+V206L、A339S+R320K+R458K+Y295F、A339S+R320 K+S323T+V206L、A339S+R320K+S323T+Y295F、A339S+R320K+V206L+Y295F、<h2 style=";text-align:left;direction:ltr">A339S+R458K+S323T+V206L, A339S+R458K+S323T+Y295F, A339S+R458K+V206L+Y295F, A339S+S323T+V206L+Y295F, G109A+G149A+G182T+H1*, G109A+G149A+G182T+I9M, G109A+G149A+G182T+K391A, G109A+G149A+G182T+M202L, G,<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">109A+G149A+G182T+N16Y、G109A+G149A+G182T+N195F、G109A+G149A+G182T+N54S、G109A+G149A+G182T+Q169E、G109A+G149A+G182T+Q169E、G109A+ G149A+G182T+Q172K、G109A+G149A+G182T+Q299Y、G109A+G149A+G182T+Q345R、G109A+G149A+G182T+Q365S、G109A+G149A+G182T+R320K、G109A+G14 9A+G182T+R458K、G109A+G149A+G182T+S323T、G109A+G149A+G182T+V206L、G109A+G149A+G182T+Y295F、G109A+G149A+H1*+I9M、G109A+G149A+H1*+ K391A, G109A+G149A+H1*+M202L, G109A+G149A+H1*+N16Y, G109A+G149A+H1*+N195F, G109A+G149A+H1*+N54S, G109A+G149A+H1*+Q169E, G109A+G149 A+H1*+Q169E、G109A+G149A+H1*+Q172K、G109A+G149A+H1*+Q299Y、G109A +G149A+H1*+Q345R、G109A+G149A+H1*+Q365S、G109A+G149A+H1*+R320K、G 109A+G149A+H1*+R458K、G109A+G149A+H1*+S323T、G109A+G149A+H1*+V206L、G109A+G149A+H1*+Y295F、G109A+G149A+I9M+K391A、G109A+G149A+I9M +M202L、G109A+G149A+I9M+N16Y、G109A+G149A+I9M+N195F、G109A+G149A+I9M+N54S、G109A+G149A+I9M+Q169E、G109A+G149A+I9M+Q169E、G109A+G1 49A+I9M+Q172K、G109A+G149A+I9M+Q299Y、G109A+G149A+I9M+Q345R、G109A+G149A+I9M+Q365S、G109A+G149A+I9M+R320K、G109A+G149A+I9M+R458K、<h2 style=";text-align:left;direction:ltr">G109A+G149A+I9M+S323T、G109A+G149A+I9M+V206L、G109A+G149A+I9M+Y295F、G109A+G149A+K391A+M202L、G109A+G149A+K391A+N16Y、G109A+G149 A+K391A+N195F、G109A+G149A+K391A+N54S、G109A+G149A+K391A+Q169E、 G109A+G149A+K391A+Q169E、G109A+G149A+K391A+Q172K、G109A+G149A+K3 91A+Q299Y、G109A+G149A+K391A+Q345R、G109A+G149A+K391A+Q365S、G109A+G149A+K391A+R320K、G109A+G149A+K391A+R458K、G109A+G149A+K391A +S323T, G109A+G149A+K391A+V206L, G109A+G149A+K391A+Y295F, G109A+G149A+M202L+N16Y, G109A+G149A+M202L+N195F, G109A+G149A+M202L+N54S G109A+G149A+M202L+Q169E, G109A+G149A+M202L+Q169E, G109A+G149A+M202L+Q172K, G109A+G149A+M202L+Q299Y, G109A+G149A+M202L+Q345R, G1 09A+G149A+M202L+Q365S、G109A+G149A+M202L+R320K、G109A+G149A+M202L+R458K、G109A+G149A+M202L+S323T、G109A+G149A+M202L+V206L、G109A+ G149A+M202L+Y295F、G109A+G149A+N16Y+N195F、G109A+G149A+N16Y+N54S、G109A+G149A+N16Y+Q169E、G109A+G149A+N16Y+Q169E、G109A+G149A+N1 6Y+Q172K、G109A+G149A+N16Y+Q299Y、G109A+G149A+N16Y+Q345R、G109A+G149A+N16Y+Q365S、G109A+G149A+N16Y+R320K、G109A+G149A+N16Y+R458K、<h2 style=";text-align:left;direction:ltr">G109A+G149A+N16Y+S323T、G109A+G149A+N16Y+V206L、G109A+G149A+N16Y+Y295F、G109A+G149A+N195F+N54S、G109A+G149A+N195F+Q169E、G109A+G1 49A+N195F+Q169E、G109A+G149A+N195F+Q172K、G109A+G149A+N195F+Q299Y、G109A+G149A+N195F+Q345R、G109A+G149A+N195F+Q365S、G109A+G149A+ N195F+R320K, G109A+G149A+N195F+R458K, G109A+G149A+N195F+S323T, G109A+G149A+N195F+V206L, G109A+G149A+N195F+Y295F, G109A+G149A+N54S 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style=";text-align:left;direction:ltr">G109A+G182T+N54S+V206L、G109A+G182T+N54S+Y295F、G109A+G182T+Q169E+Q169E、G109A+G182T+Q169E+Q172K、G109A+G182T+Q169E+Q299Y、G109 A+G182T+Q169E+Q345R、G109A+G182T+Q169E+Q365S、G109A+G182T+Q169E +R320K、G109A+G182T+Q169E+R458K、G109A+G182T+Q169E+S323T、G109A+G 182T+Q169E+V206L、G109A+G182T+Q169E+Y295F、G109A+G182T+Q169E+Q172K、G109A+G182T+Q169E+Q299Y、G109A+G182T+Q169E+Q345R、G109A+G182 T+Q169E+Q365S、G109A+G182T+Q169E+R320K、G109A+G182T+Q169E+R458K 、G109A+G182T+Q169E+S323T、G109A+G182T+Q169E+V206L、G109A+G182T+Q 169E+Y295F、G109A+G182T+Q172K+Q299Y、G109A+G182T+Q172K+Q345R、G109A+G182T+Q172K+Q365S、G109A+G182T+Q172K+R320K、G109A+G182T+Q17 2K+R458K、G109A+G182T+Q172K+S323T、G109A+G182T+Q172K+V206L、G109A+G182T+Q172K+Y295F、G109A+G182T+Q299Y+Q345R、G109A+G182T+Q299Y+ Q365S、G109A+G182T+Q299Y+R320K、G109A+G182T+Q299Y+R458K、G109A+G182T+Q299Y+S323T、G109A+G182T+Q299Y+V206L、G109A+G182T+Q299Y+Y29 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+N16Y、G109A+H1*+K391A+N195F、G109A+H1*+K391A+N54S、G109A+H1*+K391A+Q169E、G109A+H1*+K391A+Q169E、G109A+H1*+K391A+Q172K、G109A+H1 *+K391A+Q299Y、G109A+H1*+K391A+Q345R、G109A+H1*+K391A+Q365S、G109A+H1*+K391A+R320K、G109A+H1*+K391A+R458K、G109A+H1*+K391A+S323T、<h2 style=";text-align:left;direction:ltr">G109A+H1*+K391A+V206L、G109A+H1*+K391A+Y295F、G109A+H1*+M202L+N16Y、G109A+H1*+M202L+N195F、G109A+H1*+M202L+N54S、G109A+H1*+M202L +Q169E、G109A+H1*+M202L+Q169E、G109A+H1*+M202L+Q172K、G109A+H1*+M 202L+Q299Y、G109A+H1*+M202L+Q345R、G109A+H1*+M202L+Q365S、G109A+H 1*+M202L+R320K、G109A+H1*+M202L+R458K、G109A+H1*+M202L+S323T、G109A+H1*+M202L+V206L、G109A+H1*+M202L+Y295F、G109A+H1*+N16Y+N195F、 G109A+H1*+N16Y+N54S、G109A+H1*+N16Y+Q169E、G109A+H1*+N16Y+Q169E、 G109A+H1*+N16Y+Q172K、G109A+H1*+N16Y+Q299Y、G109A+H1*+N16Y+Q345R 、G109A+H1*+N16Y+Q365S、G109A+H1*+N16Y+R320K、G109A+H1*+N16Y+R45 8K、G109A+H1*+N16Y+S323T、G109A+H1*+N16Y+V206L、G109A+H1*+N16Y+Y2 95F、G109A+H1*+N195F+N54S、G109A+H1*+N195F+Q169E、G109A+H1*+N195F 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+H1*+Q172K+R320K、G109A+H1*+Q172K+R458K、G109A+H1*+Q172K+S323T、G109A+H1*+Q172K+V206L、G109A+H1*+Q172K+Y295F、G109A+H1*+Q299Y+Q3 45R、G109A+H1*+Q299Y+Q365S、G109A+H1*+Q299Y+R320K、G109A+H1*+Q29 9Y+R458K、G109A+H1*+Q299Y+S323T、G109A+H1*+Q299Y+V206L、G109A+H1* +Q299Y+Y295F、G109A+H1*+Q345R+Q365S、G109A+H1*+Q345R+R320K、G109A+H1*+Q345R+R458K、G109A+H1*+Q345R+S323T、G109A+H1*+Q345R+V206L、G109A+H1*+Q345R+Y295F、G109A+H1*+Q365S+R320K、G109A+H1*+Q365S+R458K、G109A+H1*+Q365S+S323T、G109A+H1*+Q365S+V206L、G109A+H1*+Q365S+Y295F、G109A+H1*+R320K+R458K、G109A+H1*+R320K+S323T、G109A+H1*+R320K+V、 <h2 style=";text-align:left;direction:ltr">206L、G109A+H1*+R320K+Y295F、G109A+H1*+R458K+S323T、G109A+H1*+R4 58K+V206L、G109A+H1*+R458K+Y295F、G109A+H1*+S323T+V206L、G109A+H 1*+S323T+Y295F、G109A+H1*+V206L+Y295F、G109A+I9M+K391A+M202L、G109A+I9M+K391A+N16Y、G109A+I9M+K391A+N195F、G109A+I9M+K391A+N54S、 G109A+I9M+K391A+Q169E、G109A+I9M+K391A+Q169E、G109A+I9M+K391A+Q 172K、G109A+I9M+K391A+Q299Y、G109A+I9M+K391A+Q345R、G109A+I9M+K3 91A+Q365S、G109A+I9M+K391A+R320K、G109A+I9M+K391A+R458K、G109A+I9M+K391A+S323T、G109A+I9M+K391A+V206L、G109A+I9M+K391A+Y295F、G10 9A+I9M+M202L+N16Y、G109A+I9M+M202L+N195F、G109A+I9M+M202L+N54S、G109A+I9M+M202L+Q169E、G109A+I9M+M202L+Q169E、G109A+I9M+M202L+Q 172K, G109A+I9M+M202L+Q299Y, G109A+I9M+M202L+Q345R, G109A+I9M+M202L+Q365S, G109A+I9M+M202L+R320K, G109A+I9M+M202L+R458K, G109A+I9 M+M202L+S323T、G109A+I9M+M202L+V206L、G109A+I9M+M202L+Y295F、G10 9A+I9M+N16Y+N195F、G109A+I9M+N16Y+N54S、G109A+I9M+N16Y+Q169E、G10 9A+I9M+N16Y+Q169E、G109A+I9M+N16Y+Q172K、G109A+I9M+N16Y+Q299Y、G109A+I9M+N16Y+Q345R、G109A+I9M+N16Y+Q365S、G109A+I9M+N16Y+R320K、<h2 style=";text-align:left;direction:ltr">G109A+I9M+N16Y+R458K、G109A+I9M+N16Y+S323T、G109A+I9M+N16Y+V206L、G109A+I9M+N16Y+Y295F、G109A+I9M+N195F+N54S、G109A+I9M+N195F+Q16 9E、G109A+I9M+N195F+Q169E、G109A+I9M+N195F+Q172K、G109A+I9M+N195F +Q299Y、G109A+I9M+N195F+Q345R、G109A+I9M+N195F+Q365S、G109A+I9M+N1 95F+R320K, G109A+I9M+N195F+R458K, G109A+I9M+N195F+S323T, G109A+I9M+N195F+V206L, G109A+I9M+N195F+Y295F, G109A+I9M+N54S+Q169E, G109A +I9M+N54S+Q169E、G109A+I9M+N54S+Q172K、G109A+I9M+N54S+Q299Y、G109A+I9M+N54S+Q345R、G109A+I9M+N54S+Q365S、G109A+I9M+N54S+R320K、G109 A+I9M+N54S+R458K、G109A+I9M+N54S+S323T、G109A+I9M+N54S+V206L、G109A+I9M+N54S+Y295F、G109A+I9M+Q169E+Q169E、G109A+I9M+Q169E+Q172K、 G109A+I9M+Q169E+Q299Y、G109A+I9M+Q169E+Q345R、G109A+I9M+Q169E+Q365S、G109A+I9M+Q169E+R320K、G109A+I9M+Q169E+R458K、G109A+I9M+Q169E +S323T, G109A+I9M+Q169E+V206L, G109A+I9M+Q169E+Y295F, G109A+I9M+Q169E+Q172K, G109A+I9M+Q169E+Q299Y, G109A+I9M+Q169E+Q345R, G109A+I 9M+Q169E+Q365S、G109A+I9M+Q169E+R320K、G109A+I9M+Q169E+R458K、G10 9A+I9M+Q169E+S323T、G109A+I9M+Q169E+V206L、G109A+I9M+Q169E+Y295F、<h2 style=";text-align:left;direction:ltr">G109A+I9M+Q172K+Q299Y、G109A+I9M+Q172K+Q345R、G109A+I9M+Q172K+Q365S、G109A+I9M+Q172K+R320K、G109A+I9M+Q172K+R458K、G109A+I9M+Q1 72K+S323T, G109A+I9M+Q172K+V206L, G109A+I9M+Q172K+Y295F, G109A+I9M+Q299Y+Q345R, G109A+I9M+Q299Y+Q365S, G109A+I9M+Q299Y+R320K, G10 9A+I9M+Q299Y+R458K、G109A+I9M+Q299Y+S323T、G109A+I9M+Q299Y+V206L、G109A+I9M+Q299Y+Y295F、G109A+I9M+Q345R+Q365S、G109A+I9M+Q345R+ R320K, G109A+I9M+Q345R+R458K, G109A+I9M+Q345R+S323T, G109A+I9M+Q345R+V206L, G109A+I9M+Q345R+Y295F, G109A+I9M+Q365S+R320K, G109A+I 9M+Q365S+R458K、G109A+I9M+Q365S+S323T、G109A+I9M+Q365S+V206L、G1 09A+I9M+Q365S+Y295F、G109A+I9M+R320K+R458K、G109A+I9M+R320K+S32 3T、G109A+I9M+R320K+V206L、G109A+I9M+R320K+Y295F、G109A+I9M+R458 K+S323T、G109A+I9M+R458K+V206L、G109A+I9M+R458K+Y295F、G109A+I9M+ S323T+V206L、G109A+I9M+S323T+Y295F、G109A+I9M+V206L+Y295F、G109A+K391A+M202L+N16Y、G109A+K391A+M202L+N195F、G109A+K391A+M202L+N5 4S、G109A+K391A+M202L+Q169E、G109A+K391A+M202L+Q169E、G109A+K391 A+M202L+Q172K、G109A+K391A+M202L+Q299Y、G109A+K391A+M202L+Q345R、<h2 style=";text-align:left;direction:ltr">G109A+K391A+M202L+Q365S、G109A+K391A+M202L+R320K、G109A+K391A+M202L+R458K、G109A+K391A+M202L+S323T、G109A+K391A+M202L+V206L、G1 09A+K391A+M202L+Y295F、G109A+K391A+N16Y+N195F、G109A+K391A+N16Y+N54S、G109A+K391A+N16Y+Q169E、G109A+K391A+N16Y+Q169E、G109A+K391 A+N16Y+Q172K、G109A+K391A+N16Y+Q299Y、G109A+K391A+N16Y+Q345R、G1 09A+K391A+N16Y+Q365S、G109A+K391A+N16Y+R320K、G109A+K391A+N16Y+R 458K, G109A+K391A+N16Y+S323T, G109A+K391A+N16Y+V206L, G109A+K391A+N16Y+Y295F, G109A+K391A+N195F+N54S, G109A+K391A+N195F+Q169E, G1 09A+K391A+N195F+Q169E、G109A+K391A+N195F+Q172K、G109A+K391A+N195F+Q299Y、G109A+K391A+N195F+Q345R、G109A+K391A+N195F+Q365S、G109 A+K391A+N195F+R320K、G109A+K391A+N195F+R458K、G109A+K391A+N195F+S323T、G109A+K391A+N195F+V206L、G109A+K391A+N195F+Y295F、G109A+K 391A+N54S+Q169E, G109A+K391A+N54S+Q169E, G109A+K391A+N54S+Q172K, G109A+K391A+N54S+Q299Y, G109A+K391A+N54S+Q345R, G109A+K391A+N54 S+Q365S、G109A+K391A+N54S+R320K、G109A+K391A+N54S+R458K、G109A+K 391A+N54S+S323T、G109A+K391A+N54S+V206L、G109A+K391A+N54S+Y295F、<h2 style=";text-align:left;direction:ltr">G109A+K391A+Q169E+Q169E、G109A+K391A+Q169E+Q172K、G109A+K391A+Q169E+Q299Y、G109A+K391A+Q169E+Q345R、G109A+K391A+Q169E+Q365S、G10 9A+K391A+Q169E+R320K、G109A+K391A+Q169E+R458K、G109A+K391A+Q169E+S323T、G109A+K391A+Q169E+V206L、G109A+K391A+Q169E+Y295F、G109A+ K391A+Q169E+Q172K, G109A+K391A+Q169E+Q299Y, G109A+K391A+Q169E+Q345R, G109A+K391A+Q169E+Q365S, G109A+K391A+Q169E+R320K, G109A+K39 1A+Q169E+R458K、G109A+K391A+Q169E+S323T、G109A+K391A+Q169E+V206L、G109A+K391A+Q169E+Y295F、G109A+K391A+Q172K+Q299Y、G109A+K391A+ Q172K+Q345R、G109A+K391A+Q172K+Q365S、G109A+K391A+Q172K+R320K、G109A+K391A+Q172K+R458K、G109A+K391A+Q172K+S323T、G109A+K391A+Q17 2K+V206L、G109A+K391A+Q172K+Y295F、G109A+K391A+Q299Y+Q345R、G109A+K391A+Q299Y+Q365S、G109A+K391A+Q299Y+R320K、G109A+K391A+Q299Y+ R458K, G109A+K391A+Q299Y+S323T, G109A+K391A+Q299Y+V206L, G109A+K391A+Q299Y+Y295F, G109A+K391A+Q345R+Q365S, G109A+K391A+Q345R+R32 0K、G109A+K391A+Q345R+R458K、G109A+K391A+Q345R+S323T、G109A+K391A+Q345R+V206L、G109A+K391A+Q345R+Y295F、G109A+K391A+Q365S+R320K、<h2 style=";text-align:left;direction:ltr">G109A+K391A+Q365S+R458K、G109A+K391A+Q365S+S323T、G109A+K391A+Q365S+V206L、G109A+K391A+Q365S+Y295F、G109A+K391A+R320K+R458K、G109A+K391A+R320K+S323T、G109A+K391A+R320K+V206L、G109A+K391A+R320K+Y295F、G109、<h2 style=";text-align:left;direction:ltr"> A+K391A+R458K+S323T、G109A+K391A+R458K+V206L、G109A+K391A+R458K+Y295F、G109A+K391A+S323T+V206L、G109A+K391A+S323T+Y295F、G109A+K391A+V206L+Y295F、G109A+M202L+N16Y+N195F、G109A+M202L+N16Y+N54S、G109A+M202L+N16Y+Q169E、G109A+M202L+N16Y+Q169E、G109A+M202L+N16Y+Q172K、G109A+M202L+N16Y+Q299Y、G109A+M202L+N16Y+Q345R、G109A+M202L+N16Y+Q365S、G109A+M202L+N16Y+R320K、G109A+M202L+N16Y+R458K、G109A+M202L+N16Y+S323T、G109A+M202L+N16Y+V206L、G109A+M202L+N16Y+Y295F、G109A+M202L+N195F+N54S、G109A+M202L+N195F+Q169E、G109A+M202L+N195F+Q169E、G109A+M202L+N195F+Q172K、G109A+M202L+N195F+Q299Y、G109A+M202L+N195F+Q345R、G109A+M202L+N195F+Q365S、G109A+M202L+N195F+R320K、G109A+M202L+N195F+R458K、G109A+M202L+N195F+S323T、G109A+M202L+N195F+V206L、G109A+M202L+N195F+Y295F、G109A+M202L+N54S+Q169E、G109A+M202L+N54S+Q169E、G109A+M202L+N54S+Q172K、G109A+M202L+N54S+Q299Y、G109A+M202L+N54S+Q345R、G109A+M202L+N54S+Q365S、G109A+M202L+N54S+R320K、G109A+M202L+N54S+R458K、G109A+M202L+N54S+S323T、G109A+M202L+N54S+V206L、G109A+M202L+N54S+Y295F、<h2 style=";text-align:left;direction:ltr">G109A+M202L+Q169E+Q169E、G109A+M202L+Q169E+Q172K、G109A+M202L+Q 169E+Q299Y、G109A+M202L+Q169E+Q345R、G109A+M202L+Q169E+Q365S、G10 9A+M202L+Q169E+R320K、G109A+M202L+Q169E+R458K、G109A+M202L+Q169E+S323T、G109A+M202L+Q169E+V206L、G109A+M202L+Q169E+Y295F、G109A+ M202L+Q169E+Q172K, G109A+M202L+Q169E+Q299Y, G109A+M202L+Q169E+Q345R, G109A+M202L+Q169E+Q365S, G109A+M202L+Q169E+R320K, G109A+M20 2L+Q169E+R458K、G109A+M202L+Q169E+S323T、G109A+M202L+Q169E+V206L、G109A+M202L+Q169E+Y295F、G109A+M202L+Q172K+Q299Y、G109A+M202L+ Q172K+Q345R, G109A+M202L+Q172K+Q365S, G109A+M202L+Q172K+R320K, G109A+M202L+Q172K+R458K, G109A+M202L+Q172K+S323T, G109A+M202L+Q17 2K+V206L、G109A+M202L+Q172K+Y295F、G109A+M202L+Q299Y+Q345R、G109A+M202L+Q299Y+Q365S、G109A+M202L+Q299Y+R320K、G109A+M202L+Q299Y+ R458K, G109A+M202L+Q299Y+S323T, G109A+M202L+Q299Y+V206L, G109A+M202L+Q299Y+Y295F, G109A+M202L+Q345R+Q365S, G109A+M202L+Q345R+R32 0K、G109A+M202L+Q345R+R458K、G109A+M202L+Q345R+S323T、G109A+M202L+Q345R+V206L、G109A+M202L+Q345R+Y295F、G109A+M202L+Q365S+R320K、<h2 style=";text-align:left;direction:ltr">G109A+M202L+Q365S+R458K、G109A+M202L+Q365S+S323T、G109A+M202L+Q365S+V206L、G109A+M202L+Q365S+Y295F、G109A+M202L+R320K+R458K、G10 9A+M202L+R320K+S323T、G109A+M202L+R320K+V206L、G109A+M202L+R320K+Y295F、G109A+M202L+R458K+S323T、G109A+M202L+R458K+V206L、G109A+M 202L+R458K+Y295F、G109A+M202L+S323T+V206L、G109A+M202L+S323T+Y295F、G109A+M202L+V206L+Y295F、G109A+N16Y+N195F+N54S、G109A+N16Y+N1 95F+Q169E、G109A+N16Y+N195F+Q169E、G109A+N16Y+N195F+Q172K、G109A+N16Y+N195F+Q299Y、G109A+N16Y+N195F+Q345R、G109A+N16Y+N195F+Q365S G109A+N16Y+N195F+R320K, G109A+N16Y+N195F+R458K, G109A+N16Y+N195F+S323T, G109A+N16Y+N195F+V206L, G109A+N16Y+N195F+Y295F, G109A+N1 6Y+N54S+Q169E、G109A+N16Y+N54S+Q169E、G109A+N16Y+N54S+Q172K、G109A+N16Y+N54S+Q299Y、G109A+N16Y+N54S+Q345R、G109A+N16Y+N54S+Q365S、 G109A+N16Y+N54S+R320K、G109A+N16Y+N54S+R458K、G109A+N16Y+N54S+S323T、G109A+N16Y+N54S+V206L、G109A+N16Y+N54S+Y295F、G109A+N16Y+Q16 9E+Q169E、G109A+N16Y+Q169E+Q172K、G109A+N16Y+Q169E+Q299Y、G109A+N 16Y+Q169E+Q345R、G109A+N16Y+Q169E+Q365S、G109A+N16Y+Q169E+R320K、<h2 style=";text-align:left;direction:ltr">G109A+N16Y+Q169E+R458K、G109A+N16Y+Q169E+S323T、G109A+N16Y+Q169 E+V206L、G109A+N16Y+Q169E+Y295F、G109A+N16Y+Q169E+Q172K、G109A+N1 6Y+Q169E+Q299Y、G109A+N16Y+Q169E+Q345R、G109A+N16Y+Q169E+Q365S、G 109A+N16Y+Q169E+R320K、G109A+N16Y+Q169E+R458K、G109A+N16Y+Q169E+ S323T, G109A+N16Y+Q169E+V206L, G109A+N16Y+Q169E+Y295F, G109A+N16Y+Q172K+Q299Y, G109A+N16Y+Q172K+Q345R, G109A+N16Y+Q172K+Q365S, G1 09A+N16Y+Q172K+R320K、G109A+N16Y+Q172K+R458K、G109A+N16Y+Q172K+S323T、G109A+N16Y+Q172K+V206L、G109A+N16Y+Q172K+Y295F、G109A+N16Y+ Q299Y+Q345R、G109A+N16Y+Q299Y+Q365S、G109A+N16Y+Q299Y+R320K、G109A+N16Y+Q299Y+R458K、G109A+N16Y+Q299Y+S323T、G109A+N16Y+Q299Y+V2 06L, G109A+N16Y+Q299Y+Y295F, G109A+N16Y+Q345R+Q365S, G109A+N16Y+Q345R+R320K, G109A+N16Y+Q345R+R458K, G109A+N16Y+Q345R+S323T, G109A +N16Y+Q345R+V206L、G109A+N16Y+Q345R+Y295F、G109A+N16Y+Q365S+R320K、G109A+N16Y+Q365S+R458K、G109A+N16Y+Q365S+S323T、G109A+N16Y+Q36 5S+V206L、G109A+N16Y+Q365S+Y295F、G109A+N16Y+R320K+R458K、G109A+N16Y+R320K+S323T、G109A+N16Y+R320K+V206L、G109A+N16Y+R320K+Y295F、<h2 style=";text-align:left;direction:ltr">G109A+N16Y+R458K+S323T、G109A+N16Y+R458K+V206L、G109A+N16Y+R458K+Y295F、G109A+N16Y+S323T+V206L、G109A+N16Y+S323T+Y295F、G109A+N1 6Y+V206L+Y295F、G109A+N195F+N54S+Q169E、G109A+N195F+N54S+Q169E、G109A+N195F+N54S+Q172K、G109A+N195F+N54S+Q299Y、G109A+N195F+N54S+ Q345R, G109A+N195F+N54S+Q365S, G109A+N195F+N54S+R320K, G109A+N195F+N54S+R458K, G109A+N195F+N54S+S323T, G109A+N195F+N54S+V206L, G10 9A+N195F+N54S+Y295F、G109A+N195F+Q169E+...

Claims

1. α-amylase variants of a parent α-amylase polypeptide, The mutant is Using SEQ ID NO: 1 for numbering, the following: H1*+N16Y+N54S+V56T+G109A+Q169E+Q172K+A174*+N195F+M202L+V206L+K391A, H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+N195F+M202L+V206L+K391A, H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+N195F+M202L+V206L+Q365S+K391A, H1*+I9M+N54S+V56T+G109A+G149A+Q169E+Q172K+A174*+G182T+N195F+M20 2L+V206L+Y295F+Q299Y+R320K+S323T+A339S+Q345R+Q365S+K391A+R458K, H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+N195F+M202L+V206L+R320S+K391A, H1* + N54S + V56T + G109A + Y160H + Q169E + Q172K + A174* + N195F + M202L + V206L + K391A, and H1*+I9M+N54S+V56T+G109A+Q169E+Q172K+A174*+N195F+M202L+V206L+K391A, is selected from the group consisting of having 90% or more (but less than 100%) sequence identity to the polypeptides of SEQ ID NOs: 1-17; and has α-amylase activity, and an improvement factor (IF) of at least 3.0 in an ADW detergent composition containing a bleaching agent when compared to said parent α-amylase, and said parent α-amylase has the amino acid sequence set forth in SEQ ID NO:

2. The α-amylase variant.

2. 2. The α-amylase variant of claim 1, wherein the variant comprises deletions at two or more positions corresponding to positions R181, G182, D183, and G184, using SEQ ID NO: 1 for numbering.

3. A composition comprising the variant of claim 1 and at least one other active ingredient.

4. The composition of claim 3, wherein the composition is a detergent, and the detergent composition is a liquid laundry detergent composition, a powder laundry detergent composition, a liquid dishwashing detergent composition, or a powder dishwashing detergent composition.

5. 5. The composition of claim 3 or 4, wherein the composition is a liquid or powder automatic dishwashing (ADW) detergent composition.

6. 3. The use of a variant according to claim 1 or 2 in a domestic or industrial cleaning process. Or use of the composition according to any one of claims 3 to 5.

7. A method for removing stains from fabrics or hard surfaces, comprising contacting the fabric or hard surface contaminated with the stain with a composition according to any one of claims 3 to 5.

8. 6. A method of washing dishes in an automatic dishwashing machine using a composition according to any one of claims 3 to 5, comprising the steps of adding the detergent composition into a detergent composition compartment of the automatic dishwashing machine and discharging the detergent composition during a main wash cycle.

9. 6. A method of washing laundry in an automatic washing machine using a composition according to any one of claims 3 to 5, comprising the steps of adding said detergent composition into a detergent composition compartment of said automatic washing machine and discharging said detergent composition during a main wash cycle.

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