Process for preparation of gamma, delta-unsaturated aldehyde derivatives

Abstract

The present invention relates to the field of organic synthesis, and more particularly, to a method for preparing a compound of formula (II) starting from a compound of formula (I), and to a method for preparing a compound of formula (I) by means of valuable novel chemical intermediates, such as compounds of formula (IV) and compounds of formula (V). Compounds of Formula (IV) and compounds of Formula (V) are also part of the invention.

Description

TECHNICAL FIELD

[0001] The present invention relates to the field of organic synthesis, more particularly to a process for the preparation of a compound of formula (II) starting from a compound of formula (I), and to a process for the preparation of a compound of formula (I) starting from a compound of formula (III) via valuable new chemical intermediates such as compounds of formula (IV) and compounds of formula (V). The compounds of formula (IV) and (V) are also part of the present invention. BACKGROUND

[0002] In the perfumery industry, there is a constant need to provide compounds that impart a completely new organoleptic note. In particular, there is a great interest in ingredients that can impart the scent of lily of the valley or at least one of the key organoleptic facets of lily of the valley. There is therefore a particular need for compounds that impart said note to reproduce the delicate floral scent of muguet, which cannot be preserved even by the mildest extraction methods, and which cannot be extracted as an essential oil. For this purpose, the compound of formula (II) has been previously reported in WO2010 / 052635 or WO2015 / 000821. The process for the preparation of said compound involves, first, a Johnson-Claisen rearrangement reaction, followed by a reduction and oxidation reaction, which requires the use of non-catalytic and toxic reagents such as hydrides or pyridinium chlorochromate; or a direct Claisen rearrangement reaction. However, the target intermediates or products obtained in the rearrangement step are obtained in moderate to low yields.

[0003] These products have an important industrial value, and there is therefore a constant need to develop new processes that allow to improve the yield and the production efficiency. At the same time, there is also a need to promote sustainable processes, such as the use of enzymatic conversions.

[0004] The present invention solves the above-mentioned problems by using an oxidoreductase in the process for the preparation of a compound of formula (II). The process disclosed herein represents a new way of preparing the compound via a new intermediate that has never been disclosed before, while improving the yield and reducing the environmental impact. To the best of our knowledge, the conditions of the present invention, as well as the compounds of formula (IV) and (V) that are the object of the present invention, have never been reported in the prior art. SUMMARY

[0005] The present invention relates to a new process that allows to prepare a compound of formula (II) in high yield and high selectivity, starting from a compound of formula (III), via compounds of formula (IV), (V) and (I). The process of the present invention represents a new way of efficiently synthesizing a compound of formula (II).

[0006] It is therefore the first object of the present application a process for the reduction by hydrogenation of a conjugated dienals of formula (I)

[0007]

[0008] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 and R 3 independently of one another represent a hydrogen atom, a C 1-3 alkyl group, a C 1-6 alkoxy group or a C 2-6 alkenyl group, each of which is optionally substituted with a hydroxyl group or a C 1-3 alkoxy group; or R 1 and R 2 together form a C 3-8 cycloalkyl group or a C 5-8 cycloalkenyl group; R 4 , R 5 and R 6 independently of one another represent a hydrogen atom, a methyl group or an ethyl group;

[0009]

[0010] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 to R 6 have the same meaning as defined in formula (I);

[0011] The process is carried out in the presence of an oxidoreductase.

[0012] The second object of the present application is a process for the preparation of a compound of formula (I),

[0013]

[0014] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 and R 3 independently of one another represent a hydrogen atom, a C 1-3 alkyl group, a C 1-6 alkoxy group or a C 2-6 alkenyl group, each of which is optionally substituted with a hydroxyl group or a C 1-3 alkoxy group; or R 1 and R 2 together form a C 3-8 cycloalkyl group or a C 5-8 cycloalkenyl group; R 4 , R 5 and R 6independently of one another represent a hydrogen atom, a methyl group or an ethyl group;

[0015] comprising the steps of:

[0016] a) converting a compound of formula (III) into an acetal of formula (IV),

[0017]

[0018] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 , R 3 , R 4 and R 5 have the same meaning as defined in formula (I);

[0019]

[0020] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 , R 3 , R 4 and R 5 have the same meaning as defined in formula (I); R a and R b independently of one another represent a C 1-4 alkyl group, or R a and R b together represent a C 2-5 alkanediyl group;

[0021] b) treating the acetal obtained in step a) with an acid and a compound of formula R 6 -CH=CH-OR c , wherein R 6 has the same meaning as defined in formula (I) and R c represents a C 1-4 alkyl group,

[0022]

[0023] in the form of any one of its stereoisomers or a mixture thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R a , R b and R c have the same meaning as defined above; and

[0024] c) treating the compound of formula (V) with an acid to obtain the compound of formula (I).

[0025] A third object of the application is a compound of formula (IV),

[0026]

[0027] in the form of any one of its stereoisomers or a mixture thereof, and in which R 1 , R 2 and R 3 represent, independently of one another, a hydrogen atom, a C 1-3 alkoxy group, a C 1-6 alkyl group or a C 2-6 alkenyl group, each of which is optionally substituted with a hydroxyl group or a C 1-3 alkoxy group; or R 1 and R 2 together form a C 3-8 cycloalkyl group or a C 5-8 cycloalkenyl group; R 4 and R 5 are, independently of one another, a hydrogen atom, a methyl group or an ethyl group; R a and R b represent, independently of one another, a C 1-4 alkyl group, or R a and R b together represent a C 2-5 alkanediyl group.

[0028] Another object of the application is a compound of formula (V),

[0029]

[0030] in the form of any one of its stereoisomers or a mixture thereof, and in which R 1 , R 2 and R 3 represent, independently of one another, a hydrogen atom, a C 1-3 alkoxy group, a C 1-6 alkyl group or a C 2-6 alkenyl group, each of which is optionally substituted with a hydroxyl group or a C 1-3 alkoxy group; or R 1 and R 2 together form a C 3-8 cycloalkyl group or a C 5-8 cycloalkenyl group; R 4 , R 5 and R 6 represent, independently of one another, a hydrogen atom, a methyl group or an ethyl group; R a and R b represent, independently of one another, a C1-4 Alkyl, or R a and R b When put together, it represents C 2-5 Alkyl; R c Representing C 1-4 alkyl.

[0031] Another object of the present invention is a compound of formula (I) and / or formula (II) and an oxidoreductase.

[0032] Another object of the present invention is a reaction medium comprising an oxidoreductase according to the invention and compounds of formula (I) and / or formula (II).

[0033] Another object of the present invention is a compound of formula (II) that can be obtained by the method of the present invention. Detailed Implementation

[0034] It has now been surprisingly discovered that the flavoring component of formula (II) can be obtained from a new class of precursors (or chemical intermediates) as defined in formulas (IV) and (V) below, which can yield the corresponding flavoring component in a higher overall yield and under more sustainable reaction conditions compared to methods known in the prior art.

[0035] Therefore, the first object of the present invention is a reduction method for hydrogenating the conjugated diene aldehyde of formula (I) to the deconjugated diene aldehyde of formula (II).

[0036]

[0037] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R 2 and R 3 Each independently represents a hydrogen atom and a carbon atom. 1-3 Alkoxy, C 1-6 Alkyl or C 2-6 Alkenyl groups, each optionally substituted with a hydroxyl group or a C group. 1-3 alkoxy; or R 1 and R 2 Together they form C 3-8 cycloalkyl or C 5-8 Cycloalkenyl; R 4 R 5 and R 6 Each can independently represent a hydrogen atom, a methyl group, or an ethyl group;

[0038]

[0039] in the form of any one of its stereoisomers or mixtures thereof, and wherein R 1 to the meaning of the definitions in formula (I); 6 to the meaning of the definitions in formula (I);

[0040] The method is carried out in the presence of an oxidoreductase.

[0041] For the sake of clarity, by the expression "any one of its stereoisomers or mixtures thereof" or similar expressions, it is meant the usual meaning understood by the person skilled in the art, i.e. the compounds of formula (I) and (II) can be pure enantiomers, or mixtures of enantiomers. In other words, the compounds of formula (I) and (II) can have at least one stereocenter which can have two different stereochemistries (e.g. R or S). The compounds of formula (I) and (II) can even be in the form of pure enantiomers, or in the form of mixtures of enantiomers. When the compounds of formula (I) and (II) have more than one stereocenter, the compounds of formula (I) and (II) can even be in the form of pure diastereomers, or in the form of mixtures of diastereomers. The compounds of formula (I) and (II) can be in the racemic form or in the scalemic form. Thus, the compounds of formula (I) and (II) can be one stereoisomer, or in the form of a composition of matter comprising or consisting of various stereoisomers.

[0042] For the sake of clarity, by the wavy bond in the compound of formula (II) or similar compounds, it is meant the usual meaning understood by the person skilled in the art, i.e. the double bond can have a cis configuration corresponding to the Z isomer, a trans configuration corresponding to the E isomer, or mixtures thereof. In other words, the compound of formula (II) can be in the form of its E or Z isomer, or in the form of a mixture thereof, e.g. the method of the present application leads to a composition of matter consisting of one or more compounds of formula (II) having the same chemical structure but different configuration of the double bond. In particular, the compound (II) can be in the form of a mixture of isomers E and Z, wherein said isomer E represents at least 25%, at least 35%, at least 50% or even at least 75% of the total mixture (i.e. the mixture E / Z is comprised between 75 / 25 and 100 / 0), even at least 88%, even at least 95%.

[0043] The terms "alkyl" and "alkenyl" are to be understood as including both branched and straight-chain alkyl and alkenyl groups. The terms "alkenyl" and "cycloalkenyl" are to be understood as comprising 1, 2 or 3 olefinic double bonds, preferably 1 or 2 olefinic double bonds. The terms "cycloalkyl" and "cycloalkenyl" are to be understood as including both monocyclic or fused, spiro and / or bridged bicyclic or tricyclic cycloalkyl and cycloalkenyl groups, preferably monocyclic cycloalkyl and cycloalkenyl groups.

[0044] For the sake of clarity, by the expression "R 1 and R 2 together form a C 3-8 cycloalkyl or C 5-8 cycloalkenyl", it is meant that the carbon atom to which the two groups are bound is included in the C 5-8 cycloalkyl or C 5-8 cycloalkenyl.

[0045] The term "optionally" is to be understood as meaning that the certain group which is to be optionally substituted can or can not be substituted with a certain functional group.

[0046] According to any embodiment of the application, R 4 may be a hydrogen atom or a methyl group. More particularly, R 4 may be a hydrogen atom.

[0047] According to any embodiment of the application, R 5 may be a methyl group or an ethyl group. More particularly, R 5 may be a methyl group.

[0048] According to any embodiment of the application, R 6 may be a hydrogen atom or a methyl group. More particularly, R 6 may be a hydrogen atom.

[0049] According to any embodiment of the application, R 3 may be, independently of each other, a hydrogen atom, a methoxy group, an ethoxy group, a C 1-4 alkyl group or a C 2-4 alkenyl group, each of which is optionally substituted with a hydroxyl group, a methoxy group or an ethoxy group. In particular, R 3 may be, independently of each other, a hydrogen atom, a C 1-3 alkyl group or a C 2-3 alkenyl group, each of which is optionally substituted with a hydroxyl group or a methoxy group. In particular, R 3 may be, independently of each other, a hydrogen atom or a C 1-3 alkyl group. In particular, R 3 may be, independently of each other, a hydrogen atom or a methyl group or an ethyl group. Even more particularly, R 3 may be a hydrogen atom.

[0050] According to any embodiment of the application, the compound of formula (I) complies with the following formula:

[0051]

[0052] in the form of any one of its stereoisomers or a mixture thereof, and wherein each R 1 and R 2The meaning is the same as the definition above;

[0053] Furthermore, the compound of formula (II) conforms to the following formula:

[0054]

[0055] The compound is in the form of any one of its stereoisomers or mixtures thereof, and each R 1 and R 2 The meaning is the same as the definition above.

[0056] According to any embodiment of the invention, R 1 They can independently be hydrogen atoms, methoxy groups, ethoxy groups, and C atoms. 1-4 Alkyl or C 2-4 Alkenyl groups, each optionally substituted with a hydroxyl, methoxy, or ethoxy group. Specifically, R... 1 They can be independent of each other as hydrogen atoms and C atoms. 1-3 Alkyl or C 2-3 Alkenyl groups, each optionally substituted with a hydroxyl or methoxy group. Specifically, R 1 They can be hydrogen atoms or carbon atoms independently of each other. 1-3 Alkyl group. Specifically, R 1 They can be hydrogen atoms or methyl or ethyl atoms independently of each other. Even more specifically, R 1 It can be methyl.

[0057] According to any embodiment of the invention, R 2 They can independently be hydrogen atoms, methoxy groups, ethoxy groups, and C atoms. 1-4 Alkyl or C 2-4 Alkenyl groups, each optionally substituted with a hydroxyl, methoxy, or ethoxy group. Specifically, R... 2 They can be independent of each other as hydrogen atoms and C atoms. 1-3 Alkyl or C 2-3 Alkenyl groups, each optionally substituted with a hydroxyl or methoxy group. Specifically, R 2 They can be hydrogen atoms or carbon atoms independently of each other. 1-3 Alkyl group. Specifically, R 2 They can be hydrogen atoms or methyl or ethyl atoms independently of each other. Even more specifically, R 2 It can be a hydrogen atom.

[0058] Non-limiting examples of compounds of Formula (II) can include: (E)-4-methyl-5-(p- tolyl)pent-4-enal, (4E)-2,4-dimethyl-5-(4-methylphenyl)-4-pentenal, (4E)-4-methyl-5-(3- methylphenyl)-4-pentenal, (E)-5-(4-ethylphenyl)-4-methylpent-4-enal, (E)-5-(4- isopropylphenyl)-4-methylpent-4-enal, (E)-5-(4-methoxyphenyl)-4-methylpent-4- enal, (E)-5-(2,3-dihydro-lH-inden-5-yl)-4-methylpent-4-enal, (E)-5-(l,l-dimethyl-2,3- dihydro-lH-inden-5-yl)-4-methylpent-4-enal, (Z)-4-methyl-5-(p-tolyl)pent-4-enal, (4Z)- 2,4-dimethyl-5-(4-methylphenyl)-4-pentenal, (4Z)-4-methyl-5-(3-methylphenyl)-4- pentenal, (Z)-5-(4-ethylphenyl)-4-methylpent-4-enal, (Z)-5-(4-isopropylphenyl)-4- methylpent-4-enal, (Z)-5-(4-methoxyphenyl)-4-methylpent-4-enal, (Z)-5-(2,3-dihydro- lH-inden-5-yl)-4-methylpent-4-enal, (Z)-5-(l,l-dimethyl-2,3-dihydro-lH-inden-5-yl)-4- methylpent-4-enal, 4-methyl-5-(p-tolyl)pent-4-enal, 2,4-dimethyl-5-(4-methylphenyl)- 4-pentenal, 4-methyl-5-(3-methylphenyl)-4-pentenal, 5-(4-ethylphenyl)-4-methylpent- 4-enal, 5-(4-isopropylphenyl)-4-methylpent-4-enal, 5-(4-methoxyphenyl)-4- methylpent-4-enal, 5-(2,3-dihydro-lH-inden-5-yl)-4-methylpent-4-enal, or 5-(l,l- dimethyl-2,3-dihydro-lH-inden-5-yl)-4-methylpent-4-enal.

[0059] Non-limiting examples of compounds of Formula (I) can include: (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal, (2E,4E)-2,4-dimethyl-5-(p-tolyl)pent-2,4-dienal, (2E,4E)-4-methyl-5-(m-tolyl)pent-2,4-dienal, (2E,4E)-5-(4-ethylphenyl)-4-methylpent-2,4-dienal, (2E,4E)-5-(4-isopropylphenyl)-4-methylpent-2,4-dienal, (2E,4E)-5-(4-methoxyphenyl)-4-methylpent-2,4-dienal, (2E,4E)-5-(2,3-dihydro-lH-inden-5-yl)-4-methylpent-2,4-dienal, (2E,4E)-5-(l,l-dimethyl-2,3-dihydro-lH-inden-5-yl)-4-methylpent-2,4-dienal, (2E,4Z)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal, (2E,4Z)-2,4-dimethyl-5-(p-tolyl)pent-2,4-dienal, (2E,4Z)-4-methyl-5-(m-tolyl)pent-2,4-dienal, (2E,4Z)-5-(4-ethylphenyl)-4-methylpent-2,4-dienal, (2E,4Z)-5-(4-isopropylphenyl)-4-methylpent-2,4-dienal, (2E,4Z)-5-(4-methoxyphenyl)-4-methylpent-2,4-dienal, (2E,4Z)-5-(2,3-dihydro-lH-inden-5-yl)-4-methylpent-2,4-dienal, (2E,4Z)-5-(l,l-dimethyl-2,3-dihydro-lH-inden-5-yl)-4-methylpent-2,4-dienal, (2Z,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal, (2Z,4E)-2,4-dimethyl-5-(p-tolyl)pent-2,4-dienal, (2Z,4E)-4-methyl-5-(m-tolyl)pent-2,4-dienal, (2Z,4E)-5-(4-ethylphenyl)-4-methylpent-2,4-dienal, (2Z,4E)-5-(4-isopropylphenyl)-4-methylpent-2,4-dienal, (2Z,4E)-5-(4-methoxyphenyl)-4-methylpent-2,4-dienal, (2Z,4E)-5-(2,3-dihydro-lH-inden-5-yl)-4-methylpent-2,4-dienal, (2Z,4E)-5-(l,l-dimethyl-2,3-dihydro-lH-inden-5-yl)-4-methylpent-2,4-dienal, 4-methyl-5-(4-methylphenyl)-2,4-pentadienal, 2,4-dimethyl-5-(p-tolyl)pent-2,4-dienal, 4-methyl-5-(m-tolyl)pent-2,4-dienal, 5-(4-isopropylphenyl)-4-methylpent-2,4-dienal, 5-(4-methoxyphenyl)-4- methylpent-2,4-dienal, 5-(2,3-dihydro-lH-inden-5-yl)-4-methylpent-2,4-dienal, 5-(l,l- dimethyl-2,3-dihydro-lH-inden-5-yl)-4-methylpent-2,4-dienal.

[0060] The term "polypeptide" refers to a contiguous polymer of amino acid residues, such as an amino acid sequence of at least 15 residues, at least 30 residues, at least 50 residues. In some embodiments herein, a polypeptide comprises an amino acid sequence that is an enzyme, a fragment thereof, or a variant thereof.

[0061] The term "protein" refers to an amino acid sequence of any length, wherein the amino acids are linked by covalent peptide bonds, and includes oligopeptides, peptides, polypeptides, and full-length proteins, whether naturally occurring or synthetic.

[0062] The term "isolated" polypeptide refers to an amino acid sequence removed from its natural environment by any method known in the art or combinations of these methods, including recombinant, biochemical, and synthetic methods.

[0063] The terms "nucleic acid sequence," "nucleic acid," "nucleic acid molecule," and "polynucleotide" are used interchangeably and refer to a sequence of nucleotides. A nucleic acid sequence can be a single- or double-stranded deoxyribonucleotide or ribonucleotide of any length and includes chromosomal, artificial, and synthetic DNA and / or RNA sequences, fragments, primers, and nucleic acid probes. The skilled artisan appreciates that a nucleic acid sequence of RNA is identical to a DNA sequence, with the exception that thymine (T) is replaced by uracil (U). The term "nucleotide sequence" is also understood to encompass polynucleotide molecules or oligonucleotide molecules in the form of individual fragments or as components of larger nucleic acid.

[0064] "Isolated nucleic acid" or "isolated nucleic acid sequence" refers to a nucleic acid or nucleic acid sequence that is not in its natural environment and can include those that are substantially free of contaminating endogenous material. The term "naturally-occurring" as used herein in reference to a nucleic acid refers to a nucleic acid that is found in the cells of organisms in nature and has not been intentionally modified by man in the laboratory.

[0065] A "recombinant nucleic acid sequence" refers to a nucleic acid sequence generated by combining genetic material from more than one source using laboratory methods, such as molecular cloning, thereby creating or modifying a nucleic acid sequence that does not occur naturally and cannot otherwise be found in a biological organism.

[0066] "Recombinant DNA technology" refers to molecular biology methods used to make recombinant nucleic acid sequences, such as described in Laboratory Manuals, edited by Weigel and Glazebrook, 2002, Cold Spring Harbor Lab Press; and Sambrook et al., 1989 Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

[0067] The term "gene" refers to a stretch of DNA sequence comprising a region that is transcribed into an RNA molecule, such as mRNA, in a cell, operably linked to appropriate regulatory regions, such as a promoter. Thus, a gene can comprise multiple operably linked sequences, such as a promoter, a 5' leader sequence comprising, e.g., sequences involved in translation initiation, a coding region of cDNA or genomic DNA, introns, exons, and / or a 3' untranslated sequence comprising, e.g., a transcription termination site.

[0068] "Expression of a gene" encompasses "heterologous expression" and "overexpression" and relates to transcription of the gene and translation of mRNA to protein. Overexpression refers to production of a gene product, measured at the level of mRNA, polypeptide, and / or enzyme activity, in a transgenic cell or organism that exceeds the level of production in a non-transformed cell or organism of similar genetic background.

[0069] As used herein, an "expression vector" refers to a nucleic acid molecule engineered using molecular biology methods and recombinant DNA technology to deliver foreign or exogenous DNA into a host cell. Expression vectors typically include sequences required for proper transcription of the nucleotide sequence. The coding region typically encodes a protein of interest, but can also encode RNA, such as antisense RNA, siRNA, etc.

[0070] As used herein, "expression vector" includes any linear or circular recombinant vector, including but not limited to viral vectors, bacteriophages, and plasmids. The skilled artisan is able to select an appropriate vector depending on the expression system. In one embodiment, an expression vector includes a nucleic acid of the embodiments herein operably linked to at least one "regulatory sequence" that controls transcription, translation, initiation, and termination, such as a transcriptional promoter, operator, or enhancer, or an mRNA ribosomal binding site, and optionally includes at least one selectable marker. Nucleotide sequences are "operably linked" when the regulatory sequence functions effect the transcription and / or translation of the nucleic acid of the embodiments herein.

[0071] The term "primer" refers to a short nucleic acid sequence that is hybridized to a template nucleic acid sequence and used to polymerize a nucleic acid sequence complementary to the template.

[0072] As used herein, the term "host cell" or "transformed cell" refers to a cell (or organism) that has been altered to harbor at least one nucleic acid molecule, e.g., a recombinant gene encoding a desired protein or nucleic acid sequence. The host cell is in particular a bacterial cell, a fungal cell, or a plant cell. The host cell can contain the recombinant gene integrated into the nuclear or organellar genome of the host cell. Alternatively, the host cell can also contain the recombinant gene extrachromosomally. Methods for introducing nucleic acid sequences into cells are well known in the art. For example, if the cell is a prokaryotic cell (e.g., E. coli), such methods include heat shock treatment of chemically prepared competent cells (chemical transformation) and electroporation of competent cells. Both techniques are well known and do not need further explanation. If the cell is a eukaryotic cell (e.g., a fungal cell), the most commonly used transformation methods are, for example, ATMT, PEG-mediated protoplast transformation, and electroporation.

[0073] There are very few examples of currently known oxidoreductases, in particular ene reductases, that are able to catalyze the selective reduction of conjugated dienals (a,b,y,d-diunsaturated aldehydes). These few examples typically use aliphatic substrates and at very low substrate concentrations, which are not suitable for industrial applications (see, e.g., Miyamura et al., Agric. Biol. Chem., 1984, 48, 185-192; Chaparro-Riggers et al., Adv. Synth. Catal., 2007, 349, 1521-1531).

[0074] There is only one example of the reduction of an aromatic conjugated dienals reported by Mathew et al. in 2018 (Chem. Commun. 2018, 54, 11208-11211). This example uses a very low substrate concentration of only 1 mM for the substrate screening and the tested dienals are in formula (I) with R 4R 5 and R 6 All sites contain hydrogen atoms. Furthermore, this literature reports the use of F... 420 This H2-dependent enzyme uses an uncommon cofactor and is currently unsuitable for industrial-scale application due to the lack of a suitable cofactor regeneration system. Furthermore, the authors note that the enzyme is unstable, thus this biocatalytic approach is not applicable to industrial applications. Notably, this enzyme family is not related to any known olefin reductase families, and in particular, not to any enzyme families disclosed herein.

[0075] It is well known that aryl-containing substrates are larger in size than aliphatic substrates, and these molecules have been observed to be converted by enzymes with lower efficiency. In particular, if R of formula (I) 4 R 5 and / or R 6 If the site is methyl or ethyl, then there is additional steric hindrance in the active site of the olefin reductase. Unsurprisingly, to date, no compound of formula (I) (R) has been found to be effective. 4 R 5 and / or R 6 Alkenes with methyl or ethyl groups at the methyl group can be converted by enzymes to reduce α,β-double bonds. Therefore, there is an urgent need for a highly efficient alkene reductase that can selectively reduce conjugated dienes with aryl groups.

[0076] The method for preparing compound (II) includes reducing the precursor compound of compound (I) with an oxidoreductase.

[0077] Oxidoreductases are enzymes that catalyze the transfer of electrons from one molecule, the reducing agent (also known as an electron donor), to another molecule, the oxidizing agent (also known as an electron acceptor). Oxidoreductases comprise a large class of enzymes capable of catalyzing biological redox reactions. Because many chemical and biochemical transformations involve oxidation / reduction processes, oxidoreductases hold great promise for developing biotechnological methods to synthesize desired compounds.

[0078] Oxidoreductases are classified in many different ways, mainly based on their substrates and / or modes of action. Examples include alkene reductases, ketone reductases, peroxidases, hydroxylases, oxygenases, and reductases.

[0079] Preferably, the oxidoreductase is an olefin reductase (also referred to herein as ERED).

[0080] Alkene reductases, also known as mono-alkene reductases, double bond reductases, enoate reductases, olefin reductases, enoyl reductases, or EREDs, are capable of reducing the C=C double bond in activated double bond substrates such as enals, enones, and enoate esters. They belong to different enzyme families and thus also have different EC numbers. These enzymes are either NADPH- or NADH-cofactor dependent.

[0081] The vast majority of alkene reductases belong to the Old Yellow Enzyme (EC 1.6.99.1) superfamily. Members of the Old Yellow Enzyme family are NAD(P)H-dependent oxidoreductases capable of catalyzing the stereoselective and enantioselective reduction of a,b-unsaturated ketones, aldehydes, nitroalkenes, and carboxylic acids. Old Yellow Enzymes are found in bacteria, fungi, and plants and are divided into several subfamilies based on their sequence homology and structural features. Examples of Old Yellow Enzymes are represented by SEQ ID NOs: 11 to 44.

[0082] The catalytic site of Old Yellow Enzymes carries a flavin mononucleotide (FMN) cofactor that provides the hydrogen anion to the Cb atom of the substrate. In addition, it usually contains a pair of amino acid residues (usually histidine / histidine or asparagine / histidine) that bind to the electron-withdrawing group of the substrate as hydrogen bond donors and a conserved tyrosine residue (in some cases cysteine) that is necessary for the transfer of a proton to the Ca atom during the turnover.

[0083] Accordingly, in certain embodiments, if the enzyme used in the method of the present application requires an FMN cofactor, the cofactor can be introduced into the reaction. However, in most of the operations of the present application, the culture medium provides sufficient amounts of the FMN cofactor and thus there is no need to supplement the reaction with this compound.

[0084] Other members of the alkene reductase family belong to the NAD(P)H-dependent medium-chain dehydrogenases / reductases (MDRs) family (EC 1.3.1). More specifically, SEQ ID NOs: 1 to 7 are double bond reductase-like enzymes (DBRs, cd08295), while SEQ ID NOs: 8 to 10 belong to the prostaglandin dehydrogenase subfamily (PGDHs, cd05288). The MDR family of EREDs does not contain any bound cofactor (e.g. FMN) and has been shown to be capable of catalyzing the reduction of C=C double bonds in a,b-unsaturated ketones, aldehydes, and carboxylic acids.

[0085] This is the first time that the MDR family of EREDs is reported to be capable of specifically reducing the a,b-double bond in compounds of formula (I). Accordingly, one embodiment of the present application is wherein the ERED is a MDR.

[0086] One preferred embodiment of the present application is wherein the ene reductase (ERED) has at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to any one of SEQ ID NOs: 1 to 44.

[0087] It is known to those skilled in the art that ERED reactions generally require a co-factor. In the present context, a "co-factor" refers to a non-proteinaceous compound that acts in conjunction with an ERED enzyme. Suitable co-factors for use with ERED enzymes in the present method include, but are not limited to, NADP + (Nicotinamide adenine dinucleotide phosphate), NADPH (Reduced form of NADP + ), NAD + (Nicotinamide adenine dinucleotide), and NADH (Reduced form of NAD + ). Typically, if the method does not use a co-factor regeneration system (see below), the reduced form of the co-factor is added to the reaction mixture.

[0088] One embodiment of the present method is wherein the ERED reduction is performed in the presence of a co-factor; preferably, the co-factor is NAD(P)H or NAD(P) + .

[0089] The reduced form of NAD(P)H can be regenerated from the oxidized form of NAD(P) + using a co-factor regeneration system, as appropriate. One advantage of using a co-factor regeneration system is that the system can push the equilibrium of the present method towards the production of the desired product. In this way, the present method can be more optimized, more efficient, and thus more time- and cost-efficient in terms of the reagents used, as compared to not using a co-factor regeneration system.

[0090] Thus, one embodiment of the present method is wherein the ERED reduction is performed in the presence of a co-factor regeneration system.

[0091] The term "co-factor regeneration system" refers to a set of reactants that participate in a reduction reaction that reduces the oxidized form of a co-factor (e.g., reduces NAD(P) + to NAD(P)H). The co-factor oxidized by the substrate reduction reaction catalyzed by the ERED can be regenerated to its reduced state by the co-factor regeneration system. The co-factor regeneration system comprises a stoichiometric reductant that is a source of reducing hydrogen equivalents and is capable of reducing the oxidized form of the co-factor. The co-factor regeneration system can also comprise a catalyst, such as a co-factor regeneration enzyme, that catalyzes the reduction reaction of the reductant to the oxidized form of the co-factor. It is known in the art that NAD + or NADP +Co-factor regeneration systems that regenerate NADH or NADPH, respectively, can be used in the methods described herein.

[0092] The co-factor regeneration system can be in vivo or in vitro. While not wishing to be bound to any particular embodiment, examples of in vivo co-factor regeneration systems include a co-factor regeneration enzyme that catalyzes the reduction of the oxidized state of the co-factor by an ERED, which is synthesized in a cell that synthesizes the ERED enzyme. Thus, co-factor regeneration can be achieved within a single cell. In such embodiments, the cell is genetically engineered to express both the ERED enzyme and the co-factor regeneration enzyme. Examples of polypeptide sequences that encode ERED enzymes are provided herein. Preferably, the co-factor regeneration enzyme is an alcohol dehydrogenase (ADH), a formate dehydrogenase (FDH), a glucose dehydrogenase (GDH), a phosphite dehydrogenase, or a 6-phosphogluconate dehydrogenase, and examples of such enzymes and their polypeptide sequences are well known in the art. Traditionally, wild-type organisms (e.g., baker's yeast) have been used to reduce olefins with glucose and the like as co-substrates.

[0093] Alternatively, the co-factor regeneration system can be an in vitro system. In such embodiments, the ERED enzyme and the co-factor regeneration enzyme are synthesized in two separate cells or in a single cell. The enzyme (or enzymes) are then added to the reaction medium in the form of whole cells, a crude or cell-free lysate, or a purified recombinant protein (optionally immobilized), along with the co-factor and the co-substrate, to carry out the methods of the application in vitro.

[0094] Accordingly, another aspect of the application includes a reaction medium comprising a redox enzyme as defined herein and a compound of formula (I) and / or formula (II). The reaction medium can further comprise a co-factor regeneration system as described herein. The redox enzyme can be provided in the form of a recombinant cell comprising the redox enzyme, a crude or cell-free lysate, or a purified recombinant enzyme.

[0095] One embodiment of the methods of the application is where the co-factor regeneration system comprises an alcohol dehydrogenase, a formate dehydrogenase (FDH), or a glucose dehydrogenase (GDH) system.

[0096] When the co-factor regeneration system comprises an ADH, the co-factor regeneration system can further comprise an alcohol as a substrate for the regeneration system. When the co-factor regeneration system comprises a GDH, the co-factor regeneration system can further comprise glucose as a substrate for the regeneration system. When the co-factor regeneration system comprises an FDH, the co-factor regeneration system can further comprise formate as a substrate for the regeneration system.

[0097] In some embodiments, the co-factor regeneration system can comprise a formate dehydrogenase. The terms "formate dehydrogenase" and "FDH" are used interchangeably herein to refer to an enzyme that catalyzes the oxidation of formate and NADPH to carbon dioxide and NADP+, respectively. +or NADP + NAD reduced to carbon dioxide and NADH or NADPH + or NADP + dependent enzyme. Suitable formate dehydrogenases for use as a cofactor regeneration system in the reduction reactions catalysed by the EREDs described herein include naturally occurring formate dehydrogenases as well as non-naturally occurring formate dehydrogenases.

[0098] In a preferred embodiment of the process of the application, the cofactor regeneration system is a formate dehydrogenase (FDH), such as LbFDH (the amino acid sequence of which is found in SEQ ID NO: 133, and the nucleotide sequences of which are found in SEQ ID NO: 135 and 137) and MvFDH-var (the amino acid sequence of which is found in SEQ ID NO: 134, and the nucleotide sequences of which are found in SEQ ID NO: 136 and 138).

[0099] As mentioned above, the present inventors aimed at identifying oxidoreductases, in particular EREDs, that can be used to convert a compound of formula (I) into a compound of formula (II). Several enzymes that can be used for this purpose are listed in the attached examples.

[0100] Another aspect of the application is the use of a polypeptide having oxidoreductase activity in the process of the application for the preparation of a compound of formula (II), the polypeptide comprising an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% or more sequence identity with any one of SEQ ID NO: 1 to 44, or comprising the amino acid sequence of any one of SEQ ID NO: 1 to 44.

[0101] Another aspect of the application provides an isolated polypeptide having oxidoreductase activity, comprising an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% or more sequence identity with any one of SEQ ID NO: 1 to 4, or comprising the amino acid sequence of any one of SEQ ID NO: 1 to 4. This is the first time that a polypeptide having such an amino acid sequence is demonstrated to have oxidoreductase activity.

[0102] The present application also provides use of a nucleic acid molecule in the process of the present application for preparing a compound of formula (II), the nucleic acid molecule encoding a polypeptide having oxidoreductase activity comprising a nucleotide sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more sequence identity to any one of SEQ ID NOs: 45 to 132, or the reverse complement thereof, or comprising any one of the nucleotide sequences of SEQ ID NOs: 45 to 132, or the reverse complement thereof.

[0103] Another aspect of the present application provides an isolated nucleic acid molecule encoding a polypeptide having oxidoreductase activity comprising a nucleotide sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more sequence identity to any one of SEQ ID NOs: 45 to 48 or 89 to 92, or the reverse complement thereof, or comprising any one of the nucleotide sequences of SEQ ID NOs: 45 to 48 or 89 to 92, or the reverse complement thereof. This is the first time that a nucleic acid sequence is demonstrated to encode a polypeptide having oxidoreductase activity.

[0104] One aspect herein provides a vector comprising a nucleic acid molecule described herein. In another aspect, the vector is an expression vector. In a further aspect, the vector is a prokaryotic vector, a viral vector, or a eukaryotic vector.

[0105] The present application also provides a non-human host organism or host cell comprising: (1) a nucleic acid molecule described above; or (2) an expression vector comprising the nucleic acid molecule. In one aspect, the non-human host organism or host cell is a prokaryotic cell or a eukaryotic cell. In another aspect, the host cell is a bacterial cell, a plant cell, a fungal cell, or a yeast. In yet another aspect, the bacterial cell is E. coli, and the yeast cell is S. cerevisiae.

[0106] The present application also provides a nucleotide sequence obtained by modifying any one of SEQ ID NOs: 45 to 132 or the reverse complement thereof, which nucleotide sequence encompasses any sequence obtained by modifying any one of SEQ ID NOs: 45 to 132 or the reverse complement thereof using any method known in the art, for example, by introducing any type of mutation, such as a deletion, insertion, and / or substitution mutation. The embodiments herein encompass a nucleic acid comprising a sequence obtained by mutation of SEQ ID NOs: 45 to 132 or the reverse complement thereof, provided that they contain a sequence having at least the defined sequence identity to SEQ ID NOs: 45 to 132 or the reverse complement thereof, and provided that they encode a polypeptide having oxidoreductase activity as defined in any of the embodiments described above. The mutation can be any type of mutation of these nucleic acids, for example, a point mutation, a deletion mutation, an insertion mutation, and / or a frameshift mutation of one or more nucleotides of the DNA sequence of any one of SEQ ID NOs: 45 to 132. In an embodiment, the nucleic acids of the embodiments herein can be truncated, provided that they encode a polypeptide as described herein.

[0107] A variant nucleic acid can be made to adapt the nucleotide sequence to a particular expression system. For example, if an amino acid is encoded by a particular codon, it is known that bacterial expression systems can more efficiently express the polypeptide.

[0108] Due to the degeneracy of the genetic code, more than one codon can code for the same amino acid sequence, and multiple nucleic acid sequences can code for the same protein or polypeptide, all of which DNA sequences are encompassed in an embodiment herein. Where appropriate, the nucleic acid sequence encoding the oxidoreductase can be optimized for increased expression in a host cell. For example, codons specific to the host can be used to synthesize the nucleotides in an embodiment herein to increase expression.

[0109] cDNA, genomic DNA, and RNA sequences are also provided herein. Any nucleic acid sequence encoding an oxidoreductase or a variant thereof is also referred to herein as an oxidoreductase-encoding sequence.

[0110] A fragment of a polynucleotide of any one of SEQ ID NOs: 45-132 refers to contiguous nucleotides, particularly at least 15 bp, at least 30 bp, at least 40 bp, at least 50 bp, and / or at least 60 bp in length of a polynucleotide of the embodiments herein. Particularly, a fragment of a polynucleotide comprises at least 25, more particularly at least 50, more particularly at least 75, more particularly at least 100, more particularly at least 150, more particularly at least 200, more particularly at least 300, more particularly at least 400, more particularly at least 500, more particularly at least 600, more particularly at least 700, more particularly at least 800, more particularly at least 900, more particularly at least 1000 contiguous nucleotides of a polynucleotide of the embodiments herein. Without being limiting, polynucleotide fragments herein can be used as PCR primers and / or probes, or for antisense gene silencing or RNAi.

[0111] It will be apparent to those skilled in the art that genes, including the polynucleotides described herein, can be cloned based on available nucleotide sequence information, such as that in the attached sequence listing, by methods known in the art. These methods include, for example, designing DNA primers that represent the flanking sequences of the gene, with one primer generated in the forward direction to prime synthesis of the forward strand and the other primer generated in the reverse complement direction to prime the antisense strand. Such experiments are typically performed using a heat-stable DNA polymerase enzyme, such as those used in the polymerase chain reaction. Alternatively, the DNA sequence representing the gene can be chemically synthesized and then introduced into a DNA vector molecule that can be propagated, for example, in a compatible bacterium, such as E. coli.

[0112] In related embodiments provided herein, PCR primers and / or probes for detecting a nucleic acid sequence encoding an oxidoreductase enzyme are provided. Those skilled in the art will know how to synthesize degenerate or specific PCR primer pairs to amplify a nucleic acid sequence encoding an oxidoreductase enzyme or fragment thereof based on any one of SEQ ID NOs: 45-132. A kit for detecting a nucleic acid sequence encoding an oxidoreductase enzyme can include primers and / or probes specific for a nucleic acid sequence encoding an oxidoreductase enzyme, and a protocol for using the primers and / or probes to detect a nucleic acid sequence encoding an oxidoreductase enzyme in a sample. Such detection kits can be used to determine whether a plant, organism, or cell has been modified, i.e., transformed with a sequence encoding an oxidoreductase enzyme.

[0113] To test the function of variant DNA sequences according to one embodiment herein, the sequence of interest is operably linked to a selectable or screenable marker gene and transient expression analysis is performed in protoplasts or stably transformed plants to test for expression of the reporter gene. Those skilled in the art will recognize that DNA sequences capable of driving expression are constructed as modules. Thus, expression levels of shorter DNA fragments can differ from expression levels of the longest fragment and from each other. Also provided herein are functional equivalents of the nucleic acid sequences encoding the oxidoreductase proteins provided herein, i.e., nucleotide sequences that hybridize to the nucleic acid sequence of any one of SEQ ID NOs: 45-132 under stringent conditions.

[0114] Those skilled in the art will appreciate methods for identifying homologous sequences in other organisms, as well as methods for determining the percent sequence identity between homologous sequences. These newly identified DNA molecules can then be sequenced and compared to the nucleic acid sequence of any one of SEQ ID NOs: 45-132.

[0115] The percent identity between two peptides or nucleotide sequences is a function of the number of identical amino acid or nucleotide residues in the two sequences after aligning the two sequences. An identical residue is defined as a residue in the two sequences that is the same at a given position in the alignment. The percent sequence identity used herein is calculated from the optimal alignment by dividing the number of identical residues between the two sequences by the total number of residues in the shorter sequence and multiplying by 100. The optimal alignment is the alignment with the highest possible percent identity. Gaps can be introduced into the alignment at one or more positions in one or both sequences to obtain the optimal alignment. These gaps are then considered as non-identical residues for the calculation of percent sequence identity. Alignments for determining percent amino acid or nucleic acid sequence identity can be achieved using computer programs and computer programs publicly available on the internet, for example. Preferably, the optimal alignment of protein or nucleic acid sequences and the calculation of the percent sequence identity can be achieved using the BLAST program (Tatiana et al., FEMS Microbiol Lett., 1999, 174:247-250, 1999) available from the National Center for Biotechnology Information (NCBI) at ncbi.nlm.nih.gov / BLAST / bl2seq / wblast2.cgi, set to the default parameters.

[0116] In one embodiment, also provided herein are isolated, recombinant, or synthetic polynucleotides encoding the polypeptides or variant polypeptides provided herein.

[0117] A polypeptide also means to include variant and truncated polypeptides, provided that they have oxidoreductase activity.

[0118] According to another embodiment, the at least one polypeptide having oxidoreductase activity for use in any of the embodiments described herein or encoded by a nucleic acid of any of the embodiments described herein comprises a variant amino acid sequence of any of SEQ ID NOs: 1 to 44 obtained by genetic engineering, provided that the variant has oxidoreductase activity and has the required percentage of identity to any of SEQ ID NOs: 1 to 44 described herein.

[0119] According to another embodiment, the at least one polypeptide having oxidoreductase activity for use in any of the embodiments described herein or encoded by a nucleic acid of any of the embodiments described herein is a variant of any of SEQ ID NOs: 1 to 44, which can naturally occur in other organisms, provided that it has oxidoreductase activity. As used herein, a polypeptide includes polypeptides or peptide fragments comprising the amino acid sequences identified herein, as well as truncated or variant polypeptides, provided that they have oxidoreductase activity and have at least the specified percentage of identity to the corresponding fragment of any of SEQ ID NOs: 1 to 44.

[0120] Examples of variant polypeptides are naturally occurring proteins resulting from alternative mRNA splicing events or proteolytic cleavage of the polypeptides described herein. Variations attributable to proteolysis include, for example, differences in N-terminal or C-terminal ends due to proteolytic removal of one or more terminal amino acids in the polypeptides of the embodiments described herein when expressed in different types of host cells. Polypeptides encoded by nucleic acids obtained by natural or artificial mutation of the nucleic acids of the embodiments described herein (as described below) are also encompassed by the embodiments described herein.

[0121] Polypeptide variants produced by fusion of additional peptide sequences at the amino and carboxyl termini can also be used in the methods of the embodiments herein. In particular, such fusions can enhance expression of the polypeptide, aid in purification of the protein, or increase enzymatic activity of the polypeptide in a desired environment or expression system. For example, such additional peptide sequences can be signal peptides. Another aspect encompasses methods using variant polypeptides, such as polypeptides obtained by fusion to other oligopeptides or polypeptides and / or polypeptides linked to signal peptides. Polypeptides produced by fusion to another functional protein can also be advantageously used in the methods of the embodiments herein.

[0122] Variants can also differ from the polypeptides of the embodiments herein by the addition of covalent or non-covalent modifications groups attached to the polypeptide backbone. Variants also include polypeptides that differ by the addition, deletion, or substitution of one or more amino acids that alter the biochemical properties of the polypeptides provided herein. Such variants have been designed to retain the biological activity of the polypeptides provided herein. Those of ordinary skill in the art will know how to modify an amino acid sequence and retain its biological activity.

[0123] In addition to the gene sequences shown in the sequences disclosed herein, those of skill in the art will appreciate that DNA sequence polymorphisms can exist within a particular population that can result in changes to the amino acid sequences of the polypeptides disclosed herein. Such genetic polymorphisms can exist among cells from different populations, and can also exist within the same population due to natural allelic variation. Allelic variants can also include functional equivalents.

[0124] Further embodiments also relate to molecules derived from specific disclosed nucleic acid sequence polymorphisms. These natural variations will typically result in about 1% to 5% variation in the nucleotide sequence of a gene or the amino acid sequence of a polypeptide disclosed herein. As described above, nucleic acids encoding the polypeptides of the embodiments herein, or variants thereof, are useful tools for modifying non-human host organisms or cells, and for modifying non-human host organisms or cells intended for use in the methods described herein.

[0125] The embodiments provided herein provide amino acid sequences of oxidoreductase proteins, including orthologs and paralogs, as well as methods for identifying and isolating oxidoreductase orthologs and paralogs in other organisms.

[0126] Oxidoreductase polypeptides can be obtained by extraction from any organism expressing the polypeptide using standard protein or enzyme extraction techniques. If the host organism is a unicellular organism or cell, and the polypeptides of the embodiments herein are released into the culture medium, the polypeptides can be simply collected from the culture medium, for example by centrifugation, optionally followed by a washing step, and resuspended in a suitable buffer. If the organism or cell accumulates the polypeptide within its cells, the polypeptide can be obtained by disrupting or lysing the cells, and optionally further extracting the polypeptide from the cell lysate.

[0127] According to another embodiment, at least one polypeptide having oxidoreductase activity can be used in the methods of the present application.

[0128] The functionality or activity of any oxidoreductase protein, variant, or fragment can be determined by a variety of methods. For example, the protein can be transiently or stably overexpressed in a plant, bacterial, or yeast cell to test whether the protein is active. Oxidoreductase activity can be assessed by the assay methods described in the embodiments herein to indicate functionality. Variants or derivatives of the oxidoreductase polypeptides in the embodiments herein retain oxidoreductase activity. The amino acid sequence variants of the oxidoreductases provided herein can have other desirable biological functions, such as altered substrate utilization, reaction kinetics, product distribution, or other alterations.

[0129] Further provided is at least one vector comprising the nucleic acid molecule described herein.

[0130] Also provided herein is a vector selected from the group consisting of a prokaryotic vector, a viral vector, and a eukaryotic vector.

[0131] Further provided herein is a vector that is an expression vector.

[0132] The nucleic acid sequence encoding an oxidoreductase protein in an embodiment herein can be inserted into an expression vector and / or comprised in a chimeric gene inserted into an expression vector to produce the oxidoreductase protein in a host cell or a non-human host organism. Vectors for inserting a transgene into the genome of a host cell are well known in the art, including plasmids, viruses, cosmids, and artificial chromosomes. Binary vectors or co-integrate vectors that insert a chimeric gene can also be used to transform a host cell.

[0133] An embodiment provided herein provides a recombinant expression vector comprising a nucleic acid sequence of an oxidoreductase gene, or a chimeric gene comprising a nucleic acid sequence of an oxidoreductase gene operably linked to a relevant nucleic acid sequence, such as a promoter sequence. For example, a chimeric gene comprising a nucleic acid sequence of any one of SEQ ID NOs: 45 to 132, or a variant thereof, can be operably linked to a promoter sequence suitable for expression in a plant cell, a bacterial cell, or a fungal cell, which is optionally linked to a 3’ non-translated nucleic acid sequence.

[0134] Alternatively, a promoter sequence can already be present in the vector, and thus the nucleic acid sequence to be transcribed is inserted downstream of the vector promoter sequence. The vector can be engineered to have an origin of replication, a multiple cloning site, and a selectable marker.

[0135] In an embodiment, an expression vector comprising a nucleic acid described herein can be used as a tool to transform a non-human host organism or a host cell suitable for performing the methods of the embodiments herein in vivo.

[0136] The expression vectors provided herein can be used in methods of making genetically transformed non-human host organisms and / or host cells, in non-human host organisms and / or host cells that carry the nucleic acids of the embodiments herein, and in methods of making polypeptides having the oxidoreductase activity described herein.

[0137] Recombinant non-human host organisms and host cells that are transformed to carry at least one nucleic acid of the embodiments herein such that they heterologously express or overexpress at least one polypeptide of the embodiments herein are also very useful tools for practicing the methods of the embodiments herein. Accordingly, such non-human host organisms and host cells are provided herein. Another aspect of the application therefore provides a recombinant cell comprising a compound of Formula (I) and / or Formula (II) and an oxidoreductase.

[0138] In one embodiment, a host cell or non-human host organism comprising at least one nucleic acid molecule described herein or comprising at least one vector comprising at least one nucleic acid molecule is provided.

[0139] The nucleic acids according to any of the above embodiments can be used to transform non-human host organisms and cells, and the expressed polypeptides can be any of the polypeptides described above.

[0140] In one embodiment, the non-human host organism or host cell is a prokaryotic cell. In another embodiment, the non-human host organism or host cell is a bacterial cell. In a further embodiment, the non-human host organism or host cell is E. coli.

[0141] In one embodiment, the non-human host organism or host cell is a eukaryotic cell. In another embodiment, the non-human host organism or host cell is a yeast cell. In a further embodiment, the non-human host organism or host cell is S. cerevisiae.

[0142] In one embodiment, the non-human host organism or host cell expresses a polypeptide, provided that the organism or cell is transformed to contain a nucleic acid encoding the polypeptide, the nucleic acid is transcribed into mRNA, and the polypeptide is present in the host organism or cell.

[0143] Suitable methods of transforming non-human host organisms or host cells have been described previously and are also provided herein.

[0144] To practice the embodiments herein in vivo, the host organism or host cell is cultured under conditions conducive to the production of the compound of formula (II). If the host is a unicellular organism, the conditions conducive to the production of the compound of formula (II) can include the addition of appropriate co-factors to the host culture medium. In addition, the culture medium can also be selected to maximize the synthesis of the compound of formula (II). Examples of optimal culture conditions will be described in more detail in the Examples.

[0145] The non-human host organism suitable for practicing the methods of the embodiments herein in vivo can be any non-human multicellular or unicellular organism. In one embodiment, the non-human host organism used to practice the embodiments herein in vivo is a plant, a prokaryote, or a fungus. Any plant, prokaryote, or fungus can be used. In another embodiment, the non-human host organism used to practice the methods of the embodiments herein in vivo is a microorganism. Any microorganism can be used, for example, the microorganism can be a bacterium or a yeast, such as E. coli or S. cerevisiae.

[0146] An isolated higher eukaryotic cell can also be used as a host to practice the methods of the embodiments herein in vivo. The suitable eukaryotic cell can be any non-human cell, such as a plant cell or a fungal cell.

[0147] Also provided herein is a method comprising transforming a host cell or a non-human host organism with a nucleic acid encoding a polypeptide having oxidoreductase activity, the polypeptide comprising an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to any one of SEQ ID NOs: 45-132 (preferably 45-48 or 89-92), or comprising the nucleic acid sequence of any one of SEQ ID NOs: 45-132 (preferably 45-48 or 89-92).

[0148] In one embodiment, the methods provided herein comprise culturing a non-human host organism or host cell transformed to express a polypeptide under conditions that allow for the production of the polypeptide, wherein the polypeptide comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 1-44 (preferably 1-4).

[0149] It is known that aldehydes can be reduced by endogenous ketoreductases present in host strains, such as E. coli and yeast, leading to the undesired reduction of substrates or products of the inventive method to the corresponding alcohols during in vivo and in vitro production. The efficiency of the inventive method can be improved by down-regulating, engineering or removing such ketoreductases. Examples of such ketoreductases include ADH6 and ADH7 in yeast, as well as yahK, dkgA, dkgB, yeaE, yjgB, yqhD, ybbO, yghZ, adhE, entA, gldA, fucO, eutG, adhP, yghA yiaY, ydjL, ydjJ, ybdR, yphC or betA. Multiple ketoreductases can be targeted simultaneously. Thus, one embodiment of the inventive method is, wherein the expression of one or more endogenous ketoreductases in the host cell is reduced (even not expressed), preferably the ketoreductase is selected from the group consisting of ADH6 and ADH7 in yeast, as well as yahK and dkgA, dkgB, yeaE, yjgB, yqhD, ybbO, yghZ, adhE, entA, gldA, fucO, eutG, adhP, yghA yiaY, ydjL, ydjJ, ybdR, yphC or betA.

[0150] The present application further relates to a method for the recombinant production of a polypeptide according to the present application or a functionally biologically active fragment thereof, wherein a microorganism producing the polypeptide is cultivated, expression of the polypeptide is induced, optionally by applying at least one inducer of gene expression, and the polypeptides are isolated from the cultivation. If desired, the polypeptides can also be produced in this way on an industrial scale.

[0151] The microorganisms produced according to the present application can be cultivated batchwise or in a fed-batch or repeated fed-batch process, continuously or discontinuously. An overview of known cultivation processes can be found in the textbook by Chmiel (Bioprozesstechnik 1. Einführung in die Bioverfahrenstechnik [Bioprocess technology 1. Introduction to bioprocess technology] (Gustav Fischer Verlag, Stuttgart, 1991)) or in the textbook by Storhas (Bioreaktoren und periphere Einrichtungen [Bioreactors and peripheral equipment] (Vieweg Verlag, Braunschweig / Wiesbaden, 1994)).

[0152] The media used must suitably meet the requirements of the individual strains. Descriptions of media for various microorganisms are given in the handbook "Manual of Methods for General Bacteriology" of the American Society for Bacteriology (Washington D. C., USA, 1981).

[0153] The media which can be used in accordance with the application generally comprise one or more carbon sources, nitrogen sources, inorganic salts, vitamins and / or trace elements.

[0154] Preferred carbon sources are sugars, for example monosaccharides, disaccharides or polysaccharides. Very good carbon sources are, for example, glucose, fructose, mannose, galactose, ribose, sorbose, ribulose, lactose, maltose, sucrose, raffinose, starch or cellulose. Sugars can also be added to the medium by means of complex compounds, for example molasses, or other by-products of sugar refining. It is also advantageous to add mixtures of different carbon sources. Other possible carbon sources are oils and fats, for example soybean oil, sunflower oil, peanut oil and coconut oil, fatty acids, for example palmitic acid, stearic acid or linoleic acid, alcohols, for example glycerol, methanol or ethanol, and organic acids, for example acetic acid or lactic acid.

[0155] The nitrogen source is usually an organic or inorganic nitrogen compound or a material containing these compounds. Examples of nitrogen sources include ammonia or ammonium salts, for example ammonium sulfate, ammonium chloride, ammonium phosphate, ammonium carbonate or ammonium nitrate, nitrates, urea, amino acids or complex nitrogen sources, for example corn steep liquor, soybean meal, soybean protein, yeast extract, meat extract and the like. The nitrogen source can be used alone or as a mixture.

[0156] Inorganic salt compounds which can be present in the medium include chlorides, phosphates or sulfates of calcium, magnesium, sodium, cobalt, molybdenum, potassium, manganese, zinc, copper and iron.

[0157] Inorganic sulfur compounds, for example sulfates, sulfites, dithionites, tetrathionates, thiosulfates, sulfides, and also organic sulfur compounds, for example mercaptans and thiols, can be used as sulfur sources.

[0158] Phosphoric acid, potassium dihydrogen phosphate or dipotassium hydrogen phosphate or the corresponding sodium-containing salts can be used as phosphorus sources.

[0159] Chelating agents can be added to the medium in order to keep metal ions in solution. Particularly suitable chelating agents include dihydroxyphenols, such as catechol or protocatechuate, organic acids, such as citric acid, or aminopolycarboxylic acids, such as ethylenediaminetetraacetic acid (EDTA).

[0160] The fermentation medium used according to the application usually also comprises further growth factors, such as vitamins or growth promoters, which include, for example, biotin, riboflavin, thiamine, folic acid, nicotinic acid, pantothenic acid and pyridoxine, or co-factors such as flavin mononucleotide and flavin adenine dinucleotide. Growth factors and salts are usually derived from the constituents of complex media, such as yeast extract, molasses, corn steep liquor and the like. In addition, suitable precursors can be added to the medium. The exact composition of the compounds in the medium depends to a large extent on the respective experiment and is determined individually for each specific case. Information on the optimization of the medium can be found in the textbook "Applied Microbiol. Physiology, A Practical Approach" (Ed. P. M. Rhodes, P. F. Stanbury, IRL Press (1997) p. 53-73, ISBN 0 19 963577 3). Growth media can also be obtained from commercial suppliers, such as Standard 1 (Merck) or BHI (Brain Heart Infusion, DIFCO) and the like.

[0161] All components of the medium are sterilized by heat (20 min at 1.5 bar and 121 °C) or by sterile filtration. The components can be sterilized together or individually, as required. All components of the medium can be given at the start of the cultivation or added continuously or in portions.

[0162] The cultivation temperature is usually between 15 and 45 °C, preferably between 25 and 40 °C, and can be varied or kept constant during the experiment. The pH of the medium should be in the range from 5 to 8.5, preferably around 7.0. The pH value during growth can be controlled by adding basic compounds, such as sodium hydroxide, potassium hydroxide, ammonia or aqueous ammonia, or acidic compounds, such as phosphoric acid or sulfuric acid. Antifoam agents, such as fatty acid polyglycol esters, can be used to control foaming. In order to maintain the stability of the plasmid, suitable selective substances, such as antibiotics, can be added to the medium. In order to maintain aerobic conditions, oxygen or an oxygen-containing gas mixture, such as ambient air, is supplied to the culture. The cultivation is continued until the maximum amount of the desired product has been formed. This goal is usually reached within 10 to 160 hours.

[0163] The fermentation broth is then further processed. The biomass can be completely or partially removed from the fermentation broth by separation techniques, such as centrifugation, filtration, decanting or a combination of these methods, or can be left completely in it, as required.

[0164] If the polypeptide is not secreted in the culture medium, the cells can also be lysed and the product can be obtained from the lysate by known methods for isolating proteins. The cells can optionally be disrupted by high-frequency ultrasound, high pressure, for example in a French press, by osmotic pressure, by the action of detergents, lytic enzymes or organic solvents, by a homogenizer or by a combination of several of the above-mentioned methods.

[0165] The polypeptides can be purified by known chromatographic techniques, such as size exclusion chromatography (gel filtration), for example Q-sepharose chromatography, ion exchange chromatography and hydrophobic chromatography, as well as other conventional techniques, such as ultrafiltration, crystallization, salting out, dialysis and native gel electrophoresis. Suitable methods are described, for example, in Cooper, T. G., Biochemische Arbeitsmethoden [Biochemical processes], Verlag Walter de Gruyter, Berlin, New York, or Scopes, R., Protein Purification, Springer Verlag, New York, Heidelberg, Berlin.

[0166] For the isolation of recombinant proteins, it can be advantageous to use vector systems or oligonucleotides which extend the cDNA by defined nucleotide sequences and thus encode a modified polypeptide or fusion protein, which is used, for example, for easier purification. Suitable modifications of this type are, for example, so-called "tags" which act as anchors, for example modifications known as hexahistidine anchors or epitopes which can be recognized as antibody antigens (for example, described in Harlow, E. and Lane, D., 1988, Antibodies: A Laboratory Manual. Cold Spring Harbor (N.Y.) Press). These anchors can be used to link the protein to a solid carrier, for example a polymer matrix, which can be used, for example, as a filler in a chromatography column, or can be used on microtiter plates or other carriers.

[0167] The enzymes or polypeptides according to the present application or used in the methods of the present application can be used in the processes described herein in free form or immobilized. Immobilized enzymes refer to enzymes that are fixed on an inert carrier. Suitable carrier materials include clays, clay minerals (such as kaolin), diatomaceous earth, perlite, silica, alumina, sodium carbonate, calcium carbonate, cellulose powder, anion- and cation-exchange materials, synthetic polymers (such as polystyrene), acrylic resins, phenol formaldehyde resins, polyurethanes and polyolefins (such as polyethylene and polypropylene). For the preparation of supported enzymes, the carrier material is usually in the form of finely divided particles, preferably in a porous form. The particle size of the carrier material is usually not more than 5 mm, in particular not more than 2 mm (particle size distribution curve). Similarly, when whole cells are used as catalysts, carrier-free or immobilized forms can be chosen. Carrier materials are, for example, calcium alginate and carrageenan. Enzymes and cells can also be cross-linked directly with glutaraldehyde (cross-linked enzyme aggregates, CLEAs). Corresponding and other immobilization techniques are described, for example, in J. Lalonde and A. Margolin "Immobilization of Enzymes" in K. Drauz and H. Waldmann, Enzyme Catalysis in Organic Synthesis 2002, Vol. III, 991-1032, Wiley-VCH, Weinheim. Further information on biotransformations and bioreactors for carrying out the processes according to the present application is given in Rehm et al. (Ed.) Biotechnology, 2nd Edn, Vol 3, Chapter 17, VCH, Weinheim.

[0168] The at least one oxidoreductase enzyme present in the individual steps of the process of the present application or the multi-step process defined herein can be present in a living cell that naturally or recombinantly produces the enzyme or enzymes, in a harvested cell, in a dead cell, in a permeabilized cell, in a crude cell extract, in a purified extract, or in a substantially pure or completely pure form. The at least one enzyme can be present in solution, or as an enzyme immobilized on a carrier or encapsulated. The enzyme or enzymes can be present simultaneously in soluble and / or immobilized form.

[0169] The scope of the present application also includes the use of various commercially available laboratory kits. These kits can include reagents, including ERED enzymes useful in the processes of the present application. The scope of the present application also includes, wherein the ERED enzymes are purchased from a supplier of laboratory reagents and / or enzymes. Such kit and enzyme suppliers are well known to those skilled in the art.

[0170] The process according to the application can be carried out in a common reactor known to the person skilled in the art and can be carried out in different scale ranges, for example from laboratory scale (a few milliliters to a few tens of liters of reaction volume) to industrial scale (a few liters to several thousand cubic meters of reaction volume). If the enzyme is used in the form of encapsulation by non-living, optionally permeabilized cells, in the form of a more or less purified cell extract or in purified form, a chemical reactor can be used. A chemical reactor generally allows the control of the amount of at least one enzyme, the amount of at least one substrate, the pH, the temperature and the circulation of the reaction medium. When at least one polypeptide / enzyme is present in living cells, the process will be a fermentation. In this case, the biocatalytic production will be carried out in a bioreactor (fermenter) in which the parameters necessary for the survival of the living cells (for example, culture medium with nutrients, temperature, aeration, oxygen or other gases, antibiotics, etc.) can be controlled. The person skilled in the art is familiar with chemical or bioreactors, for example using procedures for scaling up chemical or biotechnological processes from laboratory scale to industrial scale or for optimizing process parameters, which are also widely described in the literature (for biotechnological processes, see for example Crueger und Crueger, Biotechnologie - Lehrbuch der angewandten Mikrobiologie, 2. Ed., R. Oldenbourg Verlag, München, Wien, 1984).

[0171] The cells containing at least one enzyme can be permeabilized by physical or mechanical means, for example ultrasound or radiofrequency pulses, a high-pressure cell-lysing machine (French press) or chemically, for example by the presence of a hypotonic medium, a lytic enzyme and a detergent in the culture medium or a combination of these methods. Examples of detergents include digitonin, n-dodecylmaltoside, octylglycoside, Triton® X-100, Tween® 20, deoxycholate, CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate), Nonidet® P40 (ethylphenol poly(ethylene glycol ether)) and the like.

[0172] Instead of living cells, non-living biomass containing the desired biocatalyst can also be applied to the biotransformation reaction according to the application.

[0173] If at least one enzyme is immobilized, it is attached to an inert carrier as described above.

[0174] The conversion reaction can be carried out batchwise, semi-batchwise or continuously. The reactants (and optionally nutrients) can be provided at the beginning of the reaction or can be provided subsequently semi-continuously or continuously.

[0175] The reactions of the application can be carried out in aqueous, aqueous-organic or non-aqueous reaction media, depending on the particular reaction type.

[0176] The aqueous or aqueous-organic medium can comprise a suitable buffer to adjust the pH value to between 5 and 11, for example between 6 and 10.

[0177] In an aqueous-organic medium, water-miscible, partially miscible or immiscible organic solvents can be used. Examples of suitable organic solvents can be selected from aliphatic hydrocarbons having for example 5 to 8 carbon atoms, such as pentane, cyclopentane, hexane, cyclohexane, heptane, octane or cyclooctane; chlorinated hydrocarbons; aromatic hydrocarbons, such as benzene, toluene, xylene, chlorobenzene or dichlorobenzene; esters, such as ethyl acetate, isopropyl myristate; ethers, such as diethyl ether, methyl tert-butyl ether, ethyl tert-butyl ether, dipropyl ether, diisopropyl ether, dibutyl ether; tetrahydrofuran or 2-methyltetrahydrofuran; ketones and alcohols. Other media include DMF, DMSO, deep eutectic solvents or ionic liquids. Further examples are mono- or polyhydric, aromatic or aliphatic alcohols, in particular polyhydric aliphatic alcohols, such as glycerol.

[0178] In a biphasic reaction system formed with an organic solvent immiscible with water, the ratio of the aqueous phase to the organic phase can be between 20:1 and 1 :10, preferably between 10:1 and 1 :1, more preferably between 8:2 and 8:1.8.

[0179] The non-aqueous medium can be substantially free of water, i.e. can contain less than about 1 % or 0.5% by weight of water.

[0180] The biocatalytic process can also be carried out in an organic non-aqueous medium. Suitable organic solvents can be selected from aliphatic hydrocarbons having for example 5 to 8 carbon atoms, such as pentane, cyclopentane, hexane, cyclohexane, heptane, octane or cyclooctane; chlorinated hydrocarbons; aromatic hydrocarbons, such as benzene, toluene, xylene, chlorobenzene or dichlorobenzene; esters, such as ethyl acetate, isopropyl myristate; ethers, such as diethyl ether, methyl tert-butyl ether, ethyl tert-butyl ether, dipropyl ether, diisopropyl ether, dibutyl ether; tetrahydrofuran or 2-methyltetrahydrofuran; ketones and alcohols. Other media include DMF, DMSO, deep eutectic solvents or ionic liquids.

[0181] The concentration of the reactants / substrates can be adjusted according to the optimal reaction conditions, depending on the specific case of the enzyme used. For example, the initial substrate concentration can be between 0.001 and 1 M, preferably between 0.01 and 0.5 M, preferably between 0.05 and 0.2 M, preferably between 0.1 and 0.2 M.

[0182] The cofactors (e.g. NADP + , NAD +NADP (NADH, NADPH, or FMN and FAD) are added to the reaction medium. The concentration of these cofactors depends on the specific enzyme used. For example, NADP... + NAD + The concentration of cofactors such as NADH and NADPH can be 0.1 to 1.5 mM, preferably 0.2 to 1 mM; the concentration of cofactors such as FMN and FAD can be 0.5 to 50 µM, preferably 1 to 5 µM.

[0183] The reaction temperature can be adjusted to achieve optimal reaction conditions, depending on the specific enzyme used. For example, the reaction can be carried out at temperatures ranging from 0 to 70°C (e.g., 20 to 50°C or 25 to 40°C). Examples of reaction temperatures include approximately 25°C, 28°C, 30°C, approximately 35°C, approximately 37°C, approximately 40°C, approximately 45°C, approximately 50°C, approximately 55°C, and approximately 60°C.

[0184] The process can continue until the substrate and product reach equilibrium, but it can also be stopped earlier. Typical process times range from 10 minutes to 48 hours, particularly from 5 hours to 40 hours, for example from 10 hours to 30 hours, and more preferably from about 24 hours. These parameters are merely non-limiting examples of suitable process conditions.

[0185] The method of the present invention may further include the step of recovering a final product or intermediate product, which may optionally be a substantially pure form of a stereoisomer or enantiomer. The term "recovery" includes the extraction, harvesting, separation, or purification of a compound from a culture medium or reaction medium. The recovery of a compound can be carried out according to any conventional separation or purification method known in the art, including but not limited to: treatment with conventional resins (e.g., anion or cation exchange resins, nonion adsorption resins, etc.), treatment with conventional adsorbents (e.g., activated carbon, silica, silica gel, cellulose, alumina, etc.), pH alteration, solvent extraction (e.g., with conventional solvents such as alcohols, ethyl acetate, hexane, etc.), distillation, dialysis, filtration, concentration, crystallization, recrystallization, pH adjustment, lyophilization, etc.

[0186] As described herein, this invention is the first to apply oxidoreductases in a method for preparing compound (II). Therefore, prior to this invention, cell culture and fermentation methods comprising the recombinant cells of this invention and compound (I) were unknown in the art. A further aspect of the invention provides a cell culture medium comprising: recombinant cells containing an oxidoreductase (preferably ERED), and compounds of formula (I) and / or formula (II). The composition of such a culture medium has been disclosed above in conjunction with the operation of the method of this invention.

[0187] The identity and purity of the isolated products can be determined by known techniques, such as high performance liquid chromatography (HPLC), gas chromatography (GC), spectroscopy (e.g. IR, UV, NMR), colorimetric methods, TLC, NIRS, enzymatic or microbiological assays (see for example: Patek et al. (1994) Appl. Environ. Microbiol. 60: 133-140; Malakhova et al. (1996) Biotekhnologiya 11 27-32; und Schmidt et al. (1998) Bioprocess Engineer. 19:67-70. Ullmann's Encyclopedia of Industrial Chemistry (1996) Bd. A27, VCH: Weinheim, S. 89-90, S. 521-540, S. 540-547, S. 559-566, 575-581 und S. 581-587; Michal, G (1999) Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology, John Wiley and Sons; Fallon, A. et al. (1987) Applications of HPLC in Biochemistry in: Laboratory Techniques in Biochemistry and Molecular Biology, Bd. 17.).

[0188] Another object of the present application is a process for the preparation of a compound of formula (I),

[0189]

[0190] in the form of any one of its stereoisomers or mixtures thereof, and wherein R 1 , R 2 and R 3 independently of one another represent a hydrogen atom, a C 1-3 alkyl group, a C 1-6 alkoxy group or a C 2-6 alkenyl group, each of which is optionally substituted with a hydroxyl group or a C 1-3 alkoxy group; or R 1 and R 2 together form a C 3-8 cycloalkyl group or a C 5-8 cycloalkenyl group; R4 , R 5 and R 6 independently of one another represent a hydrogen atom, a methyl group or an ethyl group;

[0191] comprising the steps of:

[0192] a) converting a compound of formula (III) into an acetal of formula (IV),

[0193]

[0194] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 , R 3 , R 4 and R 5 have the same meaning as defined in formula (I);

[0195]

[0196] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 , R 3 , R 4 and R 5 have the same meaning as defined in formula (I); R a and R b independently of one another represent a C 1-4 alkyl group, or R a and R b together represent a C 2-5 alkanediyl group;

[0197] b) treating the acetal obtained in step a) with an acid and a compound of formula R 6 -CH=CH-OR c , wherein R 6 has the same meaning as defined in formula (I), R c represents a C 1-4 alkyl group,

[0198]

[0199] in the form of any one of its stereoisomers or a mixture thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R a , R b and Rc R2has the same meaning as defined above; and

[0200] c) treating the compound of formula (V) with an acid to give the compound of formula (I).

[0201] According to any embodiment of the application, R a and R b may independently of each other be C 1-3 alkyl. In particular, R a and R b may independently of each other be methyl or ethyl. Even more particularly, R a and R b may independently of each other be methyl.

[0202] According to any embodiment of the application, R c may be C 1-3 alkyl. In particular, R c may be methyl or ethyl. Even more particularly, R c is ethyl.

[0203] According to any embodiment of the application, the conversion of the compound of formula (III) to the acetal of formula (IV) can be performed under normal conditions known to the person skilled in the art, i.e. in the presence of an acid, such as a Bronsted acid or a Lewis acid compatible with alcohols, such as lanthanide triflate, and from orthoformic acid C 1-4 trialkylester, C 1-4 alcohol, C 2-5in the presence of a reagent selected in the group consisting of glycols and mixtures thereof. The conversion of aldehyde derivatives into the corresponding acetal is well known and largely reported in the prior art. Therefore, the person skilled in the art is able to set the optimal conditions to convert the compound of formula (III) into the compound of formula (IV). As a non-limiting example, step a) can be performed under the conditions reported in Green Chemistry, 2013, 15(10), 2740-2746; Synthesis, 2009, (23), 4082-4086; Synlett, 2002, (2), 319-321; Tetrahedron Letters, 2004, 45(26), 5135-5138; Current Organocatalysis, 2018, 5(3), 196-200 or Tetrahedron Letters, 2004, 45(44), 8141-8144. According to a particular embodiment of the application, the acid used in step a) can have a pKa lower than 3. Specific non-limiting examples of Brønsted acids can be selected in the group consisting of p-toluenesulfonic acid, methanesulfonic acid, camphorsulfonic acid, methane disulfonic acid, methane trisulfonic acid, 2,4-dinitrobenzenesulfonic acid. In particular, the Brønsted acid can be p-toluenesulfonic acid. Specific non-limiting examples of Lewis acids compatible with alcohols can be selected in the group consisting of metal triflates such as Al(OTf)3, lanthanide triflates such as Sc(OTf)3, Bi(OTf)3, metal tetrafluoroborates such as Zn(BF4)2, and zinc halides such as ZnCI2, ZnBR2. Formic acid C 1-4 Trialkyl esters, C 1-4 Alcohols or C 2-5 Specific non-limiting examples of diols can be selected in the group consisting of methanol, ethanol, ethylene glycol, trimethyl orthoformate, triethyl orthoformate.

[0204] Formic acid C 1-4 Trialkyl esters, C 1-4 Alcohols or C 2-5 Diols can be added to the reaction medium of the process of the application in a large concentration range. As a non-limiting example, as formic acid C 1-4 Trialkyl esters or C 2-5 Diols concentration values, can cite values ranging from about 1 to about 2 equivalents relative to the amount of substrate, preferably from 1 to about 1.5 equivalents relative to the amount of substrate. As a non-limiting example, as C 1-4 Alcohols concentration values, can cite values ranging from about 2 to about 15 equivalents relative to the amount of substrate, preferably ranging from 3 to about 5 equivalents relative to the amount of substrate. As known by the person skilled in the art, formic acid C 1-4trisalkyl ester, C 1-4 alcohol or C 2-5 The optimal concentration of the diol will depend on the nature of the latter, the nature of the substrate, the reaction temperature and the time required for the reaction.

[0205] The acid in step a) can be added to the reaction medium of the process of the application in a wide range of concentrations. As non-limiting examples, as acid concentration values, one can cite values ranging from about 0.1 to about 5 mol% relative to the amount of substrate, preferably from 0.3 to about 3 mol% relative to the amount of substrate, more preferably from 0.3 to about 1 mol% relative to the amount of substrate. As known by the person skilled in the art, the optimal concentration of the acid in step a) will depend on the nature of the latter, the nature of the substrate, the reaction temperature and the time required for the reaction. 1-4 trisalkyl ester, C 1-4 alcohol or C 2-5 diol, the reaction temperature and the time required for the reaction.

[0206] According to any embodiment of the application, the process of the application forming the compound of formula (IV) is carried out at a temperature ranging from 20°C to 55°C. In particular, the temperature is in the range from 20°C to 30°C. Of course, the person skilled in the art is also able to select the preferred temperature depending on the melting and boiling points of the starting product and of the final product and on the time required for the reaction or conversion.

[0207] The formation of the acetal can be carried out in the presence or in the absence of a solvent. When a solvent is required or used for practical reasons, any solvent stream in this type of reaction can be used for the purposes of the application. Non-limiting examples include C 6-12 aromatic solvents such as toluene, 1,3-diisopropylbenzene, cumene or pseudo-cumene or mixtures thereof, alcoholic solvents such as methanol, ethanol or mixtures thereof, hydrocarbon solvents such as cyclohexane or heptane, ethyl acetate, or etheric solvents such as methyltetrahydrofuran, tetrahydrofuran or mixtures thereof. The choice of solvent depends on the nature of the substrate and / or of the catalyst and the person skilled in the art is well able to select the most suitable solvent in each case to optimise the reaction.

[0208] According to any embodiment of the application, the treatment of the acetal of formula (IV) can be carried out using a compound of formula R 6 -CH=CH-OR c ; wherein R c and R 6 have the same meaning as defined hereinabove. Specific non-limiting examples of the acid used in step b) can be chosen from the group consisting of boron trifluoride complexes such as BF3.OEt2, BF3.OBu2, BF3.(AcOH)2or BF3.MeCN, anhydrous zinc chloride, p-toluenesulfonic acid. In particular, the acid used in step b) is a Lewis acid.

[0209] Formula R 6 -CH=CH-OR c The compound can be added to the reaction medium of the method of the present invention at a wide range of concentrations. As a non-limiting example, enol ether concentration values ​​can be listed as values ​​relative to the substrate, ranging from about 1 to about 5 equivalents, preferably from 1.0 to about 1.2 equivalents relative to the substrate. As those skilled in the art will know, Formula R... 6 -CH=CH-OR c The optimal concentration of the compound will depend on the properties of the latter, the properties of the substrate, the reaction temperature, and the reaction time required.

[0210] The acid used in step b) can be added to the reaction medium of the method of the present invention at a wide range of concentrations. As a non-limiting example, acid concentration values ​​can be listed relative to the substrate, ranging from about 0.001 mol% to about 10 mol%, preferably from 0.01 mol% to about 5 mol%. As those skilled in the art will know, the optimal concentration of the acid used in step b) will depend on the properties of the latter, the properties of the substrate, the reaction temperature, and the reaction time required.

[0211] According to any embodiment of the invention, the method for forming the formula (V) compound is carried out at a temperature between 10°C and 100°C. Specifically, the temperature is in the range of 5°C to 25°C. Of course, those skilled in the art can also select a preferred temperature based on the melting and boiling points of the starting and final products, as well as the time required for the reaction or conversion.

[0212] Step b) of the method of the present invention can be carried out with or without a solvent. Any solvent stream of this type of reaction can be used for the purposes of the present invention when a solvent is required or used for practical reasons. Non-limiting examples include C. 6-12 Aromatic solvents such as toluene, 1,3-diisopropylbenzene, cumene or pseudocumene or mixtures thereof, ethyl acetate, or ether solvents such as methyltetrahydrofuran, tetrahydrofuran or mixtures thereof, or chlorinating solvents such as dichloromethane, dichloroethane or mixtures thereof. The choice of solvent depends on the nature of the substrate and / or catalyst, and those skilled in the art can well select the most suitable solvent in each case to optimize the reaction. In particular, step b) can be carried out in the absence of a solvent.

[0213] According to any embodiment of the invention, steps a) and b) of the method of the invention are carried out in the same reactor with an acid such as boron trifluoride acetic acid complex, p-toluenesulfonic acid or camphorsulfonic acid.

[0214] According to any embodiment of the present application, the acid used in step c) can be selected from the group consisting of carboxylic acids (e.g. formic acid, acetic acid, aqueous acetic acid or propionic acid), mineral acids (e.g. aqueous sulfuric acid, sulfuric acid, aqueous hydrochloric acid). In particular, the acid used in step c) can be acetic acid.

[0215] The acid used in step c) can be added to the reaction medium of the process of the present application in a wide range of concentrations. As non-limiting example, as acid concentration values, values ranging from about 1 to about 10 equivalents relative to the amount of substrate, preferably from 3 to about 8 equivalents relative to the amount of substrate, can be cited. As known by the person skilled in the art, the optimal concentration of the acid used in step c) will depend on the nature of the latter, on the nature of the substrate, on the reaction temperature and on the time required for the reaction.

[0216] According to any embodiment of the present application, step c) can be performed in the presence of both an acid and a base. Non-limiting examples of bases are selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, sodium formate, potassium formate, sodium propionate and potassium propionate. In particular, the base added in step c) can be sodium acetate.

[0217] The base used in step c) can be added to the reaction medium of the process of the present application in a wide range of concentrations. As non-limiting example, as base concentration values, values ranging from about 1 to about 5 equivalents relative to the amount of substrate, preferably from 1 to about 2 equivalents relative to the amount of substrate, can be cited. As known by the person skilled in the art, the optimal concentration of the base used in step c) will depend on the nature of the latter, on the nature of the substrate, on the nature of the acid, on the reaction temperature and on the time required for the reaction.

[0218] According to any embodiment of the present application, the process of the present application to form a compound of formula (I) is performed at a temperature ranging from 25 °C to 150 °C. In particular, the temperature is in the range from 90 °C to 120 °C. Of course, the person skilled in the art is also able to select the preferred temperature depending on the melting and boiling points of the starting product and of the final product and on the time required for the reaction or conversion.

[0219] Step c) can be performed in the presence or in the absence of a solvent. When a solvent is required or used for practical reasons, any solvent stream in this type of reaction can be used for the purposes of the present application. Non-limiting examples include C 6-12 aromatic solvents such as toluene, 1,3-diisopropylbenzene, cumene or pseudo-cumene or mixtures thereof, alcoholic solvents such as methanol, ethanol or mixtures thereof, hydrocarbon solvents such as, but not limited to, cyclohexane or heptane, ethyl acetate, or etheric solvents such as methyltetrahydrofuran, tetrahydrofuran, 1,4-dioxane or mixtures thereof. The choice of the solvent depends on the nature of the substrate and / or of the catalyst and the person skilled in the art is well able to select the most suitable solvent in each case to optimize the reaction.

[0220] According to any embodiment of the application, the process of the application can be carried out in the same reactor; i.e. steps a) to c) can be carried out without any intermediate isolation step.

[0221] According to any embodiment of the application, the process of the application for preparing a compound of formula (I) can be carried out under batch / intermittent or continuous conditions.

[0222] The compounds of formula (IV) and (V) are generally novel compounds and have numerous advantages as described above and shown in the examples.

[0223] Therefore, another object of the present application is a compound of formula (IV),

[0224]

[0225] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 and R 3 independently of one another represent a hydrogen atom, a C 1-3 alkyl group, a C 1-6 alkoxy group or a C 2-6 alkenyl group, each of which is optionally substituted with a hydroxyl group or a C 1-3 alkoxy group; or R 1 and R 2 together form a C 3-8 cycloalkyl group or a C 5-8 cycloalkenyl group; R 4 and R 5 independently of one another are a hydrogen atom, a methyl group or an ethyl group; R a and R b independently of one another represent a C 1-4 alkyl group, or R a and R b together represent a C 2-5 alkanediyl group.

[0226] Another object of the present application is a compound of formula (V),

[0227]

[0228] in the form of any one of its stereoisomers or a mixture thereof, and wherein R 1 , R 2 and R 3 independently of one another represent a hydrogen atom, a C 1-3 alkyl group, a C 1-6 alkoxy group or a C 2-6 alkenyl group, each of which is optionally substituted with a hydroxyl group or a C1-3 alkoxy; or R 1 and R 2 Together they form C 3-8 cycloalkyl or C 5-8 Cycloalkenyl; R 4 R 5 and R 6 Each can independently represent a hydrogen atom, a methyl group, or an ethyl group; R a and R b Each represents C independently 1-4 Alkyl, or R a and R b When put together, it represents C 2-5 Alkyl; R c Representing C 1-4 alkyl.

[0229] Another object of the present invention is the use of the compound of formula (IV) for the preparation of compounds of formula (I) and (II).

[0230]

[0231] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R 2 and R 3 Each independently represents a hydrogen atom and a carbon atom. 1-3 Alkoxy, C 1-6 Alkyl or C 2-6 Alkenyl groups, each optionally substituted with a hydroxyl group or a C group. 1-3 alkoxy; or R 1 and R 2 Together they form C 3-8 cycloalkyl or C 5-8 Cycloalkenyl; R 4 and R 5 Each is independently a hydrogen atom, a methyl group, or an ethyl group; R a and R b Each represents C independently 1-4 Alkyl, or R a and R b Together they represent C 2-5 Alkyl group.

[0232] Another object of the present invention is the use of the compound of formula (V) for the preparation of compounds of formula (I) and (II).

[0233]

[0234] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R2 and R 3 Each independently represents a hydrogen atom and a carbon atom. 1-3 Alkoxy, C 1-6 Alkyl or C 2-6 Alkenyl groups, each optionally substituted with a hydroxyl group or a C group. 1-3 alkoxy; or R 1 and R 2 Together they form C 3-8 cycloalkyl or C 5-8 Cycloalkenyl; R 4 R 5 and R 6 Each can independently represent a hydrogen atom, a methyl group, or an ethyl group; R a and R b Each represents C independently 1-4 Alkyl, or R a and R b When put together, it represents C 2-5 Alkyl; R c Representing C 1-4 alkyl.

[0235] Typical methods for implementing the method of the present invention are reported in the embodiments below.

[0236] Example

[0237] The invention will now be described in further detail through the following embodiments, wherein abbreviations have their usual meanings in the art, and temperature is expressed in degrees Celsius (°C). Using 400MHz ( 1 H) and 100MHz ( 13 Bruker Avance II Ultrashield 400 plus operating at C) or 500MHz ( 1 H) and 125MHz ( 13 Bruker Avance III 500 operating at C), or at 600MHz ( 1 H) and 150MHz ( 13 NMR spectra were obtained using a Bruker Avance III 600 cryoprobe operated under C) conditions. Spectra were used as an internal reference relative to 0.0 ppm tetramethylsilane. 1 The H NMR signal shift is expressed in δ ppm, and the coupling constant (J) is expressed in Hz. It exhibits the following multiplicity: s, singlet; d, doublet; t, triplet; q, quartet; m, multiply; b, broad peak (indicating unresolved coupling), and is interpreted using Bruker Topspin software. 13C NMR data are reported in terms of chemical shifts δ ppm and hybridization from DEPT 90 and DEPT 135 experiments, C, quaternary; CH, methine; CH2, methylene; CH3, methyl.

[0238] Example 1

[0239] Preparation of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal (compound of formula (I)) according to the process of the application Example 2

[0240] a) Step 1 : Preparation of (2E)-2-methyl-3-(4-methylphenyl)-2-propenal (compound of formula (III))

[0241] A mixture of potassium hydroxide (65.2 g, 1.16 mol), methanol (1250 g) and p-tolualdehyde (2000.0 g, 16.7 mol) was heated to 45 °C. Propionaldehyde (1051 g, 18.1 mol) was added over 2 hours. 30 minutes after the end of the addition, propionic acid (49.2 g, 0.664 mol) was added and the mixture was concentrated by distillation. The mixture was cooled to 45 °C and water (400.0 g) and heptane (1335.0 g) were added under stirring. After the mixture was allowed to settle, the aqueous phase was decanted and discarded. The organic phase was washed with water (200.0 g) and concentrated by distillation. The crude product obtained (2673.8 g, GC purity: 84.1 %, orange liquid) was used directly in the next reaction.

[0242] b) Step 2: Preparation of l-[(lE)-3,3-dimethoxy-2-methyl-l-propenyl]-4- methylbenzene (compound of formula (IV))

[0243] A mixture of the crude product of step 1 (2673.8 g, 16.67 mol), p-toluene sulfonic acid (27.0 g, 0.142 mol) and methanol (670 g) was heated to 30 °C. Methyl orthoformate (1948.0 g, 18.36 mol) was added over 2 hours. 15 minutes after the end of the addition, sodium methoxide (30% solution in methanol, 33.4 g, 0.185 mol) was added and the mixture was concentrated by distillation. The crude acetal (3507.1 g, GC purity 90.8 %, dark brown liquid) was flashed (eb.: 52 ~ 126 °C, p = 40-1 mbar) to give a light yellow liquid (2914.1 g, purity: 93.1 %). The product was further purified by distillation on a 170 cm column packed with Sulzer DX packing to give the purified acetal (2670.1 g, purity: 99.6 %, mixture of E- and Z-isomers in a ratio of 17.5 / 1) as a colorless liquid.

[0244] 1H (CDCl3, 400 MHz): δ 1.86 (s, 3H), 2.34 (s, 3H), 3.35 (s, 6H), 4.62(s, 1H); 6.59 (s, 1H), 7.14 (d, J 8.1, 2H), 7.21 (d, J 8.1, 2H) ppm.

[0245] 13 C NMR (100 MHz, CDCl3): d 13.1 (q), 21.2 (q), 53.6 (q), 107.9 (d),128.4 (d), 128.9 (d), 129.0 (d), 133.6 (s), 134.1 (s), 136.5 (s)。

[0246] c) Step 3: Preparation of 1-[(1E)-5-ethoxy-3,5-dimethoxy-2-methyl-1-pentenyl]-4- methylbenzene (compound of formula (V))

[0247] Boron trifluoride acetate (2.86 g, 0.0153 mol) was added to 1-[(1E)-3,3-dimethoxy-2- methyl-1-propenyl]-4-methylbenzene (1584.0 g, 7.62 mol) cooled to 15 °C. Vinyl ethyl ether (577.0 g, 8.00 mol) was added over 3 hours. After 30 minutes from the end of the addition, sodium methoxide (30% solution in methanol, 13.7 g, 0.076 mol) was added. The mixture was heated to 25 °C for 1 hour and then concentrated under reduced pressure. The crude product (2136.5 g, purity: 94.4%) was used directly in the next step.

[0248] d) Step 4: Preparation of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal (compound of formula (I))

[0249] Sodium hydroxide (30% in water, 277 g, 2.08 mol) was added to acetic acid (686.0 g, 11.4 mol, 5.5 eq) over 10 minutes. l-[(lE)-5-ethoxy-3,5-dimethoxy-2-methyl-l-pentenyl]-4- methylbenzene (600.0 g, 2.08 mol) was added and the mixture was heated to reflux for 23 hours. The mixture was concentrated, water (233.3 g) and heptane (420.0 g) were added slowly at 80 °C and the mixture was allowed to stand to precipitate. The aqueous phase was decanted and discarded. The organic phase was washed with 120.0 g of water. The mixture was azeotropically dried, cooled to 40 °C and a small amount of product crystals were added as seed crystals. The mixture was cooled to -20 °C. The slurry was filtered and the filter cake was washed with cold (-20 °C) heptane (100.0 g). The crystals were dried under vacuum. Yield: 314.3 g of yellow crystals (melting point: 63 °C) (purity: 98.4%).

[0250] 1 H (CDCl3, 100 MHz): δ 2.08 (s, 3H), 2.37 (s, 3H), 6.24 (dd, J 15.3,7.7, 1H), 6.90 (s, 1H), 7.20 (d, J 7.9, 2H), 7.29 (d, J 15.3, 1H), 7.29 (d, J7.9, 2H), 9.62 (d, J 7.7, 1H) ppm.

[0251] 13 C NMR (100 MHz, CDCl3): d 13.9 (q), 21.3 (q), 127.8 (d), 129.2 (d),129.7 (d), 133.4 (s), 133.7 (s), 138.4 (s), 141.0 (d), 158.2 (d), 193.9 (d)ppm.

[0252] Production of ene reductases

[0253] Example 3

[0254] Codon harmonized genes encoding ene reductases (ERED) or formate dehydrogenases (FDH) from different organisms were expressed in E. coli BL21(DE3) transformed with pET derived constructs. Cultures were either screened in deep well plates or grown in shake flasks to produce biomass for biocatalytic reactions. E. coli strains harboring the constructs were inoculated into LB or TB media containing kanamycin (50 pg / mL) for pre-cultures and grown at 37 °C, 200 rpm overnight. Pre-cultures were inoculated into LB or TB media containing kanamycin (50 pg / mL) for main cultures at a concentration of OD 0.1 and grown at 37 °C until the optical density at 600 nm (OD600) reached approximately 0.8. Gene expression was induced with 0.1-0.2 mM IPTG (isopropyl-β-D-thiogalactopyranoside) and grown at 20-25 °C with shaking for 20 h. Cells were collected by centrifugation and resuspended in 50 mM potassium phosphate buffer (KPi, pH 7 to pH 8) to an OD value of 50 and stored at -20 °C after aliquoting. Protein expression was verified by SDS-PAGE.

[0255] Screening of ene reductases for reduction of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4- pentadienal to (4E)-4-methyl-5-(4-methylphenyl)-pent-4-enal

[0256] Example 4 Reduction of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal to (4E)-4-methyl-5- (4-methylphenyl)-pent-4-enal at higher substrate concentrations

[0257] Screening of the ERED library was performed in deep well plates with the following specific steps: whole cells equivalent to 1 mL of culture containing ERED were collected and lysed with 150 pL of lysis buffer containing lysozyme, Triton X-100 and DNase, and then directly used in 0.8 mL scale assays with the addition of 2 g / L of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal, 10 U / mL GDH, 50 mM glucose, 0.2 mM NADP + and NAD + and optionally 10% EtOH or 10% cyclohexane in 100 mM phosphate buffer at pH 7.5, overnight at 25 °C in a shaker incubator at 1000 rpm. All reactions were performed twice. Samples were extracted with 0.8 mL of ethyl acetate and analyzed by GC-FID or GC-MS.

[0258] GC-FID method: DB-1 column, 10 m x 0.1 mm, 0.1 pm; temperature gradient: 100 °C for 1 min, ramped at 25 °C / min to 300 °C, and hold at 300 °C for 2 min. Carrier gas: H2, injector temperature 250 °C, detector temperature 300 °C, split ratio and injection volume varied depending on substrate concentration. (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal and (4E)-4-methyl-5-(4-methylphenyl)-pent-4-enal were used as references.

[0259] Several of the EREDs in E. coli were active, able to fully convert (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal. Notably, the ene reductases tested were able to convert (2E,4Z)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal to (4Z)-4-methyl-5-(4-methylphenyl)-pent-4-enal.

[0260] Table 1. Conversion of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal with GDH as cofactor cycling enzyme

[0261]

[0262] In all cases, reduction of the substrate and product aldehydes to the corresponding alcohols was observed. This is most likely related to the presence of ketol reductases in E. coli. This phenomenon has been observed and described in the literature many times. As described in the background section above, one common approach to reduce alcohol formation is to downregulate or knock out the ketol reductases.

[0263] Example 5

[0264] Reduction of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal to (4E)-4-methyl-5- (4-methylphenyl)-pent-4-enal with FDH for cofactor recycling SEQUENCE LISTING

[0265] Reactions were performed in 1 mL scale at higher substrate concentrations, with the following steps: whole cells containing ERED (OD10), 20 mg / mL (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal, 10 U / mL GDH, 150 mM glucose, 1 mM NADP + , optionally 2 mM FMN, 10% toluene, 200 mM phosphate buffer (pH 8), 25 °C, 1000 rpm, overnight. All reactions were performed twice. Reaction products were extracted with EtOAc and analyzed by GC-FID as described above.

[0266] Table 2. Conversion of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal at higher substrate concentrations with GDH as the co-factor recycling enzyme

[0267]

[0268] As can be seen from Table 2, all selected enzymes were able to produce the product at higher substrate concentrations. The relative amount of alcohol produced was significantly reduced when the substrate concentration was higher.

[0269] ​

[0270] ​ ​

[0271] The most active ERED was tested with FDH for co-factor regeneration. Reactions were performed in 1 mL scale with the following steps: whole cells containing ERED (OD10), whole cells containing FDH (OD5), 20 mg / mL (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal, 1 M sodium formate, 1 mM NADP + , optionally 2 µM FMN, 10% toluene, 200 mM phosphate buffer (pH 7.5), 25°C, 1000 rpm. All reactions were performed twice. Reaction products were extracted with EtOAc and analyzed by GC-FID as described above.

[0272] Table 3. Conversion of (2E,4E)-4-methyl-5-(4-methylphenyl)-2,4-pentadienal at higher substrate concentrations with FDH as the co-factor recycling enzyme

[0273]

[0274] ​

[0275]

[0276]

[0277] Sequence

[0278] SEQ ID (ID): 1

[0279] MEEVRNKQVV FKDYINGFPK ESDMLLKSSS TICLKLPQGS NGVLVKNLYL SCDPYMRARM 60

[0280] TKTEGSYFPP FTPGSPISGY GVAKVLDSGH PDLKKGDLVW GGTGWEEYSI IDAPESLFKI 120

[0281] QHTDMPLSYY TGILGMPGMT AYIGFYEICA PKKGEYVFVS AASGAVGQLV GQFAKLSGCY 180

[0282] VVGSAGTKEK VDLLKNKFGF DEAFNYKEEQ DLNAALKRYF PDGIDIYFEN VGGKMLEAVL 240

[0283] SNMRLNGRIS ACGMISQYNL EQPEGVCNLF LLVGKRLRMQ GFIVSDYYHL YPKYMEMVMP 300

[0284] LIKQGTISYI EDIVEGLESA PAALVGLFSG RNVGKQVVVV ARE 343

[0285] Sequence ID (ID): 2

[0286] MEEVKNKQVV LKDYINGFPK ESDMLLKSSS TICLKLPQGS NGLLVKNLYL SCDPYMRNRM 60

[0287] SKSQGSYVDS LTPGLPITGY GVAKVLDSGH SDFKKGDLVW GWTGWEEYSI IDAPESLFKI 120

[0288] QHTDMPLSYY TGILGMPGMT AYAGFYEICA PKKGEYVFVS AASGAVGQLV GQFAKLSGCY 180

[0289] VVGSAGTKEK VDLLKNKFGF DEAFNYKEEQ DLNAALKRYF PDGIDIYFEN VGGKMLEAVL 240

[0290] SNMRLNGRIS ACGMISQYNL EQPEGVCNLF LLVGKRLRMQ GFIVSDYYHL YPKYMEMVMP 300

[0291] LIKQGTISYI EDIVEGLESA PAALVGLFSG RNVGKQVVVV ARE 343

[0292] SEQ ID NO: 3

[0293] MAEVVERSPE VVIVRNKQVI FKDYVNGYPK ETDMVVTSDA TIRLKLPENE SGLILTKNLY 60

[0294] LSCDPYMRGR MSKTSEGGYV PSFTPGQPIT GYGVAKVLDS GTPKFKKGDL VV GFTGWEEY SLITKTDTLFKI 120

[0295] SLIKNPELFI KIQHTDVPLS YYTGILGMAG VTAYAGFYKV AT PKKGEYVFV S AASGAVGQL V GQFAKLLGCY 180

[0296] LVGQFAKLLG CYVVGSAGSK EKVDLLKNKF GFDEAFNYKE EHDLNSTLKR CFPDGIDIYF 240

[0297] ENVGGKMLDA VLCNMRLHGR IAVCGMISQY NLNEHQGINN LIFVILKRIR MEGFLVTDHY 300

[0298] HLFPKFLEMV LPLIQEGKIT YVEDTIEGLE NAPAALVGLF SGKNVGKQIV DLTQE 355

[0299] SEQ ID NO: 4

[0300] MGEMVENKQI VLKDYVSGYP KESDMVTQVS KMSLNVPHGS NGIVVKNLYL SCDPYMRPRM 60

[0301] TKSEGGYVDS FTPGQPITGY GVAKVLDSGT PKFKKGDLVW GFTGWEEYSL ITKTDTLFKI 120

[0302] EHTDVPLSYY TGLLGMPGMT AYAGFYKVAT PKKGEYVFVS AASGAVGQLV GQFAKLLGCY 180

[0303] VVGSAGSKEK VDLLKNKFGF DEAFNYKEEE DLAAALKRYF PDGIDIYFEN VGGKMLDAVL 240

[0304] VNMRPHGRIA VCGMISQYNL EKPEGIYNLT YVIMKQLRIE GFLVFDYYHL YPKLLELVLP 300

[0305] YIKEGKINYV EDIAEGLESA PAALVGLFSG RNVGKQVVAV ARE 343

[0306] SEQ ID NO: 5

[0307] MASGGEMQVS NKQVIFRDYV TGFPKESDME LTTRSITLKL PQGSTGLLLK NLYLSCDPYM 60

[0308] RARMTNHHRL SYVDSFKPGS PIIGYGVARV LESGNPKFNP GDLVWGFTGW EEYSVITATE 120

[0309] SLFKIHNTDV PLSYYTGLLG MPGMTAYAGF YEICSPKKGE TVYVSAASGA VGQLVGQFAK 180

[0310] LTGCYVVGSA GSKEKVDLLK NKFGFDEAFN YKEEADLDAA LRRYFPDGID IYFENVGGKM 240

[0311] LDAVLPNMRP KGRIAVCGMI SQYNLEQPEG VRNLMALIVK QVRMEGFMVF SYYHLYGKFL 300

[0312] ETVLPYIKQG KITYVEDVVD GLDNAPAALI GLYSGRNVGK QVVVVSRE 348

[0313] SEQ ID NO: 6

[0314] MTATNKQVIL KDYVSGFPTE SDFDFTTTTV ELRVPEGTNS VLVKNLYLSC DPYMRIRMGK 60

[0315] PDPSTAAL A YTPGQPIQG YGVSRIIESG HPDYKKGDLL WGIVAWEEYS VITPMTHAHF 120

[0316] KIQHTDVPLS YYTGLLGMPG MTAYAGFYEV CSPKEGETVY VSAASGAVGQ LVGQLAKMMG 180

[0317] CYVVGSAGSK EKVDLLKTKF GFDDAFNYKE ESDLTAALKR CFPNGIDIYF ENVGGKMLDA 240

[0318] VLVNMNMHGR IAVCGMISQY NLENQEGVHN LSNIIYKRIR IQGFVVSDFY DKYSKFLEFV 300

[0319] LPHIREGKIT YVEDVADGLE KAPEALVGLF HGKNVGKQVV VVARE 345

[0320] Sequence ID (ID): 7

[0321] MAEEVSNKQV ILKNYVTGYP KESDMEIKNV TIKLKVPEGS NDVVVKNLYL SCDPYMRSRM 60

[0322] RKIEGSYVES FAPGSPITGY GVAKVLESGD PKFQKGDLVW GMTGWEEYSI ITPTQTLFKI 120

[0323] HDKDVPLSYY TGILGMPGMT AYAGFHEVCS PKKGETVFVS AASGAVGQLV GQFAKMLGCY 180

[0324] VVGSAGSKEK VDLLKSKFGF DEAFNYKEEQ DLSAALKRYF PDGIDIYFEN VGGKMLDAVL 240

[0325] VNMKLYGRIA VCGMISQYNL EQTEGVHNLF CLITKRIRME GFLVFDYYHL YPKYLEMVIP 300

[0326] QIKAGKVVYV EDVAHGLESA PTALVGLFSG RNIGKQVVMV SRE 343

[0327] SEQ ID NO: 8

[0328] MGQQKQRNRR WVLASRPHGA PVPENFRLEE DDVATPGEGQ VLLRTVYLSL DPYMRGRMSD 60

[0329] EPSYSPPVDI GGVMVGGTVS RVVESNHPDY QSGDWVLGYS GWQDYDISSG DDLVKLGDHP 120

[0330] QNPSWSLGVL GMPGFTAYMG LLDIGQPKEG ETLVVAAATG PVGATVGQIG KLKGCRVVGV 180

[0331] AGGAEKCRHA TEVLGFDVCL DHHADDFAEQ LAKACPKGID IYYENVGGKV FDAVLPLLNT 240

[0332] SARIPVCGLV SSYNATELPP GPDRLPLLMA TVLKKRIRLQ GFIIAQDYGH RIHEFQREMG 300

[0333] QWVKEDKIHY REEITDGLEN APQTFIGLLK GKNFGKVVIR VAGDD 345

[0334] SEQ ID NO: 9

[0335] MAPVTNGRII FNSIPTGFPV PGETTIYDTT ETIDLDTAPL DGGFLLKTLE LSVDPYMRGG 60

[0336] MRAPEKKSYS APFTLGQPLR GYGVGVVLRS ENPQVKAGDH LYGFFEHTHY SIRKDLTGLQ 120

[0337] AIENAYNLPW SVFIGVIGMP GKTAYMAWKE YAHPKQGETV FVSTGAGPVG SFVIQLAKAD 180

[0338] GLKVIASAGS EEKVQFMKEV GADVAFNYKT TNTAEVLEKE GPIDIYWDNV GGETLEAALN 240

[0339] AANVNARFIE CGMISGYNSG GAPVRNIFHV IGKSITMTGF IVSRIEPKYS AEFYKEVPAK 300

[0340] VASGELKYRE HVYNGLEKLG DVILAVQKGE NKAKAVVHVA DD 342

[0341] SEQ ID: 10

[0342] MASVTNGRVL FNSIPEGFPE PGKTVVYDTS ENIDLDTVPL NGGFLLKTLD LSIDPYMRGR 60

[0343] MRAPEKKSYS PPFLLNQPID GYGVGVVLRS ELPEVKAGDH LYGFFKHVQY DVRTNLEGLS 120

[0344] KLPNEHGLSW SVYVGAAGMP GKTAYMAWKE YSQAKKGETV FVSAGAGPVG SLVIQFAKAD 180

[0345] GLKVIGSAGS DEKVQFMKEC GADVAFNYKT TNTKEVLEKE GPIDIFWDNV GGETLEAALE 240

[0346] AANVNARFIE CGMISGYNSG GAPIRNLFHV VSKSISMHGF IVSRLEPKYG KEFYETIPHK 300

[0347] LASGELKHRE HVFDGLDKVG EALLAVQKGT NKAKAVVKVA DE 342

[0348] SEQ ID: 11

[0349] MNPKYKPLFE PFTFKSGVTI NNRIAVAPMT HYASNEDGTI SEAELDYIIP RSKEMGMVIT 60

[0350] ACANVTPDGK AFPGQPAIHD DSNIPGLKKL AQAIQAQGAK AVVQIHHGGI ECPSELVPQQ 120

[0351] DVVGPSDVFD NGKQIARALT EEEVENIVKA FGEATRRAIE AGFDGVEIHG ANGYLIQQFY 180

[0352] SPKTNQRTDR WGGSDEKRLA FPLAIVDEVK KAASEHAKGA FLVGYRLSPE EPETPGLTMT 240

[0353] ETYTLVDALG DKELDYLHIS LMDVNSKARR GADPTRTRMD LLNERVGNKV PLIAVGSIHS 300

[0354] ADDALAVIEN GIPLVAMGRE ILVDPNWTVK VKEGREKQIE TVIKGTDKEK YHLPEPLWQA 360

[0355] IVNTQGWVPY KD 372

[0356] Sequence Listing (ID): 12

[0357] MNPKYNPLFE AFTLPSGVTL KNRITMAPMT NFASHENGEV SDEELAYYRE RSGGVGAVIT 60

[0358] ACVYVTPDGK GFVNEFSADK DEMIPSLRRL ADTIHQEGAK AILQIYHGGR LCPPDQIPDG 120

[0359] QPISASAVAE EKEGAPVPRE MTSDDIHRVI RAYGEATRRA IEAGYDGVEL HGANGYLVQQ 180

[0360] FFSPHSNIRT DEWGGSLEER LTFPLAVVHE VKKVIAEHAK RPFIFGYRLS PEEGHTPGIT 240

[0361] LDDTMVLVDR LADEGLDYLH ISVNHFFGGS FRDRSDERSR TVLIHEKVGN RVPVMGVGSL 300

[0362] NTPDEALAAL ETGVPLVSLG RPLLMEPQWV QKVQNGTEDT IRTTLSKQAQ QELVIPDYLW 360

[0363] GALTTIPGWM PVTD 374

[0364] SEQ ID NO: 13

[0365] MNTELLFKPF KAGNLSLPNR IVMAPMTRNF SPQGIPGPEV AAYYRRRAEN AVGLIITEGT 60

[0366] AINHPAAVEH TSIPNFYGEG LEGWAKVVEE VHAVGGKIIP QLWHVGTARK IGADNQPNPE 120

[0367] ALPVGPSGIS PAGEKVVEPL TEAEIADIIS AYAQAAADAQ RVGFDGIELH GAHGYLIDQF 180

[0368] FWDKTNKRTD QYGGNLVQRT RFAVEVIEAC RRAVGPNFPI VLRFSQWKMY HYEEKLAQTP 240

[0369] QELEQFLTPL VKAGVDIFHC SSRRFWEPEF EGSDLNLAAW TKKITGKPVI TVGSIGLEKA 300

[0370] FLSDLEKNNN RQTDQSSSVE ARLEQLVGQV EREEADLVAV GRALLVDPAF AVKLRDQQIE 360

[0371] EIIPYSDEVL KTLN 374

[0372] SEQ ID NO: 14

[0373] MNTMLFSPYT IRGLTLKNRI VMSPMCMYSC DTKDGAVRTW HKIHYPARAV GQVGLIIVEA 60

[0374] TGVTPQGRIS ERDLGIWSDD HIAGLRELVG LVKEHGAAIG IQLAHAGRKS QVPGEIIAPS 120

[0375] AVPFDDSSPT PKEMTKADIE ETVQAFQNGA RRAKEAGFDV IEIHAAHGYL INEFLSPLSN 180

[0376] RRQDEYGGSP ENRYRFLGEV IDAVREVWDG PLFVRISASD YHPDGLTAKD YVPYAKRMKE 240

[0377] QGVDLVDVSS GAIVPARMNV YPGYQVPFAE LIRREADIPT GAVGLITSGW QAEEILQNGR 300

[0378] ADLVFLGREL LRNPYWPYAA ARELGAKISA PVQYERGWRF 340

[0379] SEQ ID NO: 15

[0380] MTGKLFSPIS VGPLSLPNRI FMAPLTRMRS REPGDVPVLP LMAEYYRQRA NAGLIISEAT 60

[0381] QVSPQGKGYM GTPGIHSAEQ VEAWRDITRA VHDEGGHIAI QLWHVGRVSH HSLQPDRQLP 120

[0382] VSASAIPYEN KTTIRGEDSK PQRVACDTPR ALRTDEIPGL IETYRQATIN AREAGFDLVE 180

[0383] VHAAHGYLLH QFQSAVSNHR DDAYGGCLEN RARLTLEVVD ACIAAWDAAH VGIRISPLGT 240

[0384] FNGLDDSAGL EMGLYLAEQL AKRNIAYLHL SEPDWAGGPA HSDEFRQALR DRFPGVIIGA 300

[0385] GNYTVEKAEA LLAKGYIDAA AFGRPYISNP DLAERFRTGA ALAMLNPATL YGGGEEGYTD 360

[0386] YPALA 365

[0387] SEQ ID NO: 16

[0388] MSGKLFTPVT IGGFTLPNRV LMAPLTRMRS SQPGDVPNEL MQAYYVQRAS AGMIIAEATQ 60

[0389] ISPQGKGYMD TPGIYSAEQV AGWKKITQAV HEANGHICLQ LWHVGRVSHH SLQPDQQLPV 120

[0390] SASAIPYENR TTVRGEDGKV KRVACDTPRA LELTEIPGLI EDYRRATVNA REAGFDMVEV 180

[0391] HAAHGYLLHQ FQSATSNQRN DAYGGSLENR ARLTLEVLDA VIGAWDAAHV GIRISPLGIF 240

[0392] NGLDDRDGLD MGLYLAEQFA LRGIGYLHLS EPDWAGGPVL NEEFRVALRA RFPGIIIAAG 300

[0393] NYSVEKAEGL LEKGLIDAAA FGRPFIANPD LPQRLRKGAE LNAVNAATLY GGGAEGYTDY 360

[0394] PALA 364

[0395] SEQ ID NO: 17

[0396] MSGKLFTPFS SGSFTFPNRV IMAPLTRMRA SQPGDIPNEL MQTYYVQRAS AGLIIAEATQ 60

[0397] ISPQGKGYMD TPGIYSAEQV QGWRKITQAV HEAGGHIALQ LWHVGRVSHH SLQPDQQLPV 120

[0398] SASAIPYQNR TTVRGEDGKP TRVDCDTPRA LELSEIPGVI EDYRRATVNS REAGFDMVEV 180

[0399] HAAHGYLLHQ FQSAESNKRE DAYGGSLENR ARLTLEALDA VIGAWDAKHV GIRISPLGTF 240

[0400] NGLDDKDGLE MALYLTREFT KRGIAYLHLS EPDWAGGPAH GDEFRQALRD AFPGTIIGAG 300

[0401] NYTVEKSEML LAKGFIDAAA FGRPFIANPD LPVRLQKGAE LNNVVAATLY GGGAEGYTDY 360

[0402] PALA 364

[0403] Sequence Listing (ID): 18

[0404] MKLLQPLQIG PLTLPNRVFM APLTRLRSLE PGDVPTTLMG EYYRQRASAG LIITEATQIS 60

[0405] FQAKGYSGSP GIHSAEQIAA WKHINEGIHA DGGHSAVQVW HTGRVSHTSL QPGGEAPVAP 120

[0406] SALPAGARTT LRDEQGDLIR VETSAPRALS EAEIAGIVAD FGLAAINARE AGFDFIELHA 180

[0407] AHGYLLHQFL TPSANQREDR YGGSVENRAR IVLEAVDAAV ANWSAERVGI RVFPLGGFNG 240

[0408] VDNGEDQEAA GLYLIRELAK RNLAYLHLSE PDWAGGKPLR DEFRQAIRAA YPGVIIAAGA 300

[0409] YTAEKGEDLI GRGLIDAVAF GRSYIANPDL VERLRLQAPL NEHRAQFDYA NGPEGYTDYP 360

[0410] FLKQA 365

[0411] SEQ ID (ID): 19

[0412] MSSEKLYSPL KVGAITAANR IFMAPLTRLR SIEPGDIPTP LMAEYYRQRA SAGLIISEAT 60

[0413] QISAQAKGYA GAPGIHSPEQ IAAWKKITAG VHAENGHMAV QLWHTGRISH ASLQPGGQAP 120

[0414] VAPSALSAGT RTSLRDENGQ AIRVETSMPR ALELEEIPGI VNDFRQAIAN AREAGFDLVE 180

[0415] LHSAHGYLLH QFLSPSSNHR TDQYGGSVEN RARLVLEVVD AGIEEWGADR IGIRVSPIGT 240

[0416] FQNTDNGPNE EADALYLIEQ LGKRGIAYLH MSEPDWAGGE PYTDAFREKV RARFHGPIIG 300

[0417] AGAYTVEKAE TLIGKGLIDA VAFGRDWIAN PDLVARLQRK AELNPQRAES FYGGGAEGYT 360

[0418] DYPTL 365

[0419] SEQ ID (ID): 20

[0420] MSAEKLFTPL KVGAVTAPNR VFMAPLTRLR SIEPGDIPTP LMGEYYRQRA SAGLIISEAT 60

[0421] QISAQAKGYA GAPGLHSPEQ IAAWKKITAG VHAEDGRIAV QLWHTGRISH SSIQPGGQAP 120

[0422] VSASALNANT RTSLRDENGN AIRVDTTTPR ALELDEIPGI VNDFRQAVAN AREAGFDLVE 180

[0423] LHSAHGYLLH QFLSPSSNQR TDQYGGSVEN RARLVLEVVD AVCNEWSADR IGIRVSPIGT 240

[0424] FQNVDNGPNE EADALYLIEE LAKRGIAYLH MSETDLAGGK PYSEAFRQKV RERFHGVIIG 300

[0425] AGAYTAEKAE DLIGKGLIDA VAFGRDYIAN PDLVARLQKK AELNPQRPES FYGGGAEGYT 360

[0426] DYPSL 365

[0427] SEQ ID NO: 21

[0428] MKTAKLFSPL KVGALTLPNR VFMAPLTRLR SIEPGDIPTP LMAEYYRQRA SAGLIITEAT 60

[0429] QISFQAKGYA GAPGLHTQEQ LNAWKKITQA VHEEGGHIAV QLWHVGRISH SSLQPGQQAP 120

[0430] VAPSAIAADT RTTVRDENGA WVRVPCSTPR ALETEEIPGI INDFRQATAN AREAGFDYIE 180

[0431] LHAAHGYLLH QFMSPASNQR TDQYGGSIEN RTRLTLEVVD ATAAQWSAER IGIRISPLGP 240

[0432] FNGLDNGEDQ EEAALYLIDE LNKRHIAYLH ISEPDWAGGK PYSEAFRDAV RARFKGVIIG 300

[0433] AGAYTAEKAE ELIEKGFIDA VAFGRSYISN PDLVARLQQH APLNEPDGET FYGGGAKGYT 360

[0434] DYPTL 365

[0435] SEQ ID NO: 22

[0436] MKTAKLFSPL KVGAFTLPNR VFMAPLTRLR SIEPGDIPTP LMAEYYAQRA SAGLIITEAT 60

[0437] QVSFQAKGYA GAPGLHTQEQ LEGWKKITQA VHEKQGHIAV QLWHVGRISH HSLQPNQQAP 120

[0438] VAPSAIAADT RTTIRDENGD WVRVPCSTPR ALELQEIPAI VDDFRNATAN AREAGFDFIE 180

[0439] IHAAHGYLLH QFMSPASNQR TDAYGGSIEN RTRLTLEVVD ATAAEWGAEH IGIRISPLGP 240

[0440] FNGLDNGEDQ EDAALYLIDE LNKRKIAYLH ISEPDWAGGK PYTDAFRDAV RARFNGIIVG 300

[0441] AGAYTAEKAE TLIEKGFIDA VAFGRSYIAN PDLVERLQQQ APLNTPDGDT FYGGGAKGYT 360

[0442] DYPTLS 366

[0443] Sequence ID (ID): 23

[0444] MTSLFDPLKI GDIQLANRIV MAPLTRNRSP GAVPNTLNAA YYEQRASAGL LITEATAISH 60

[0445] QGQGYADVPG LYKPEALEGW KQVTDAVHKA GGKIVVQMWH VGRISHDTLQ PNGGKPVAPS 120

[0446] AIRAKSKTYL INADGTGSFA ETSEPRALEK DELPGIIEDY RRAARAAVDA GFDGVEIHAA 180

[0447] NGYLLDQFLR SGSNERTDEY GGSIENRARL LFQVVDVITK EIGAGRTAIR ISPVTPANDS 240

[0448] SDPNPQPLFT YVVEGLAKYD LAYIHIIEGA TGGPRDHQQG DAPFDYAALR AAYQAAGGKA 300

[0449] AWMVNNGYNR ELAIDAVEEG KADLVAFGKL FIANPDLVER LKNDTVLNPP DQATFYGGGA 360

[0450] KGYTDYPALE NVA 373

[0451] SEQ ID NO: 24

[0452] MTKLFEPAQA GDIALANRIV MAPLTRNRSP GAIPNNLNAA YYEQRATAGL IVTEGTPVSQ 60

[0453] QGQGYADVPG LYKQEAIDGW KAVTDGVHKA GGKIVAQIWH VGRISHTSLQ PHGGQPVAPS 120

[0454] PIKANSKTYI INDDGTGSFA ETSEPREISL QEIPVILEDY RTGARAAIDA GFDGVEIHAA 180

[0455] NGYLIDQFLK SGTNQRTDAY GGSIENRARF LLEVVDTVTK EIGAGRTGIR LSPVTPANDI 240

[0456] FEADPQPLFE YVARELGSRG LAFIHVIEGA TGGPRDFKQG DKPFDYDALK AAYTNAGGKG 300

[0457] LWIANNGYDR ESAIAATESG KVDAVAFGKA FISNPDLVQR LKENAALNEP NQQTFYGGGA 360

[0458] EGYTDYPALA 370

[0459] SEQ ID NO: 25

[0460] MSDLFEPTKA GDIALANRIA MAPLTRNRSP GEAPNDLNVT YYQQRATAGL IITEGTPITH 60

[0461] QGQGYAHVPG LYKPEALEGW KKVTDAVHKA GGKIVTQIWH VGRVSHTSLQ PGEGKPVAPS 120

[0462] AITAKSKTYI INPDGSGAFA DTSEPRALSL EEIPGILEDY RVAARAAVDA GFDGVEIHAA 180

[0463] NGYLLDQFLR SGSNQRTDAY GGSIENRTRL TLEVAAVVAK EIGGGRTGIR ISPVTPANDV 240

[0464] FDPEPQPLFN HLVSKLAGLD LAFIHVIEGA TGGPRDFKQG DKPFDWDELR KTYRDAGGKG 300

[0465] AWMVNNGYDK ASATEAVASG RADIVTFGKL FIANPDLVRR FKEDAPLNEP NKATFYGGGA 360

[0466] EGYTDYPFLP 370

[0467] serial number(ID): 26

[0468] MPTLFDPLTL GDLQSPNRVL MAPLTRGRAT REHVPTELMI EYYTQRASAG LIITEATGIT 60

[0469] QEGLGWPYAP GIWSDEQVEA WKPVTQAVHE AGGRIILQLW HMGRTVHSSF LGGAKPVSSS 120

[0470] ATRAPGQAHT YEGKQDYDEA RPLSADEIPR LLNDYEHAAK NAMAAGFDGV QIHAANGYLI 180

[0471] DQFLRDNSNVRGDAYGGSIENRIRLLVEVTRRVAETVGAEKTGVRLSPNGDSQGVNDSNP 240

[0472] EPLFSAAAKA LDEIGIAHLE LREPGYEGTF GKADRPPVHP VIRQAFSRTL ILNSDYTLET 300

[0473] AQAALATGEA DAITFGRPFL ANPDLPHRFA ERLPLNKDVM ETWYSQGPEG YVDYPTADQK 360

[0474] SEQ ID NO: 27

[0475] MPTLFDPIRL GAVTAKNRIL MAPLTRGRAT RDHVPTDIMI KYYAQRASAG LIISEATGIS 60

[0476] QEGLGWPYAP GIWNEAQTQA WIPITQAVHD AGGLIFVQLW HMGRLVPSSV SGMQPVSASA 120

[0477] TKAPDLAHTY EGKKPFDVAR PLEIAEIPRL LDDYERATRN ALSAGFDGVQ IHAANGYLID 180

[0478] EFLRDGTNLR KDAYGGTPEH RIRLLREVTE RVISVIGADR TSVRLSPNGE IQGASDSHPE 240

[0479] NIFLPAARML SDLGIAFLGL REGTPEGTFG RTDQPKLSPK IREVFNPPLI LNQDYNLETA 300

[0480] QEALDSGVAD AISFGRLFIS NPDLPRRFFE GSPLIKDNIA TWYTQGAEGY TDYPLIGNEI 360

[0481] PA 362

[0482] SEQ ID NO: 28

[0483] MPSLFDPIRF GAFTAKNRIW MAPLTRGRAT RDHVPTEIMA EYYAQRASAG LIISEATGIS 60

[0484] QEGLGWPYAP GIWSDAQVEA WLPITQAVHD AGGLIFAQLW HMGRMVPSNV SGMQPVAPSA 120

[0485] SQAPGLGHTY DGKKPYDVAR ALRLDEIPRL LDDYEKAARH ALKAGFDGVQ IHAANGYLID 180

[0486] EFIRDSTNHR HDEYGGAVEN RIRLLKDVTE RVIATIGKER TAVRLSPNGE IQGTVDSHPE 240

[0487] QVFIPAAKML SDLDIAFLGM REGAVDGTFG KTDQPKLSPE IRKVFKPPLV LNQDYTFETA 300

[0488] QAALDSGVAD AISFGRPFIG NPDLPRRFFE KAPLTKDVIE TWYTQTPKGY TDYPLLGD 358

[0489] SEQ ID: 29

[0490] MTSLFEPIEL GSIYAKNRIL MAPLTRGRST RDHVPTPIMA EYYAQRAGAG LIISEATGIS 60

[0491] REGLGWPYAP GLWSQEQVEA WKPITAAVHA KGGKIVAQLW HMGRMVHSSV TGQQPVSCSA 120

[0492] TKAPEALHTY DGKQAPEVAR PLTKEDIARI LNDYENAARN ALQAGFDGVQ IHAANGYLID 180

[0493] EFLRDGTNHR SDEYGGSPEN RIRFLREVTE RVIATIGAHK TSVRLSPNGD TQGCIDSHPE 240

[0494] QVFVPASKLL NDLDIAFLEL REPGPNGTFG KTDQPKLHGP IREVFRKPLV LNQDYTREEA 300

[0495] IETVATGVAD AISFGRPFLA NPDLVRRLED NLPQNKDDIR TWYSQGAEGY TDYPLAR 357

[0496] SEQ ID NO: 30

[0497] MTTLFDPIKL GAIAAPNRII MAPLTRGRSS RGHVPSALMA EYYAQRASAG LIITEATGIS 60

[0498] QEGLGWPYAP GIWSDEQVEA WKPIVRAVHD KGGRIVMQLW HMGRMVHSNV TGLQPVSASP 120

[0499] TTAPGEAHTY DGKKPYEQAR ALDISEIPRL LADYENATRN ALAAGFDGVQ IHAANGYLID 180

[0500] EFLRDSTNKR TDAYGGEPEN RIRLLREVTE RVISVAGADR TAVRLSPNGE TQGTIDSNPI 240

[0501] SVFVPAAKML YDLGLAWLEL REPGPNGTFG RTDQPKLSPQ IRQVFKAPLV LNSDYTLEEA 300

[0502] ETAVLEDRAD AISFGRKFLA NPDLPHRFKS GLPLNRDEMK TWYSQGPQGY VDYPAAS 357

[0503] SEQ ID NO: 31

[0504] MPTLFDPIDF GPIHAKNRIV MSPLTRGRAD KEAVPTPIMA EYYAQRASAG LIITEATGIS 60

[0505] REGLGWPFAP GIWSDAQVEA WKPIVAGVHA KGGKIVCQLW HMGRMVHSSV TGTQPVSSSA 120

[0506] TTAPGEVHTY EGKKPFEQAR AIDAADISRI LNDYENAARN AIRAGFDGVQ IHAANGYLID 180

[0507] EFLRNGTNHR TDEYGGVPEN RIRFLKEVTE RVIAAIGADR TGVRLSPNGD TQGCIDSAPE 240

[0508] TVFVPAAKLL QDLGVAWLEL REPGPNGTFG KTDQPKLSPQ IRKVFLRPLV LNQDYTFEAA 300

[0509] QTALAEGKAD AIAFGRKFIS NPDLPERFAR GIALQPDDMK TWYSQGPEGY TDYPSATSGP 360

[0510] N 361

[0511] Sequence Listing (ID): 32

[0512] MPSLFDSIDL GAVHAANRII MSPLTRARAT EGAVPTPLMV EYYAQRAGAG LIISEATGIS 60

[0513] REGLGWPWAP GIWSAEQVAA WKPITKAVHE RGGKIVCQLW HMGRMVHSSV TGLQPVSASP 120

[0514] TTAPGQSHTY EGKKPYEEAR ELRVDEIPRI LADYENAARN AIEAGFDGVQ IHAANGYLID 180

[0515] EFLRDGTNHR KDEYGGAPEN RIRLLREVTE RVVATIGADR TSVRLSPNGD TQGTDDSAPE 240

[0516] KVFVPAAKVL QDLGVAWLEL REPGPEGTFG KTDEPKLSPE IRKVFSRPLV LNQDYTLEDA 300

[0517] QKAVSSGLAD AVSFGRKFIA NPDLPRRFAE EIPLAKDDMA TWYSQGPKGY TDYPFADE 358

[0518] SEQ ID NO: 33

[0519] MPNLFDPLQL GPITLPNRVI MAPLTRLRGT PDHIPTPLIA EYYAQRASAG LIISEGTPVS 60

[0520] PMGVGYAQVP GIWSEQQTEQ WSHITTAVHA AGGRIFAQIW HVGRVSHPLF LNGQQPVAPT 120

[0521] ALAPEGFVSL VRPQRPFETP RALDIAEIRS TIADYKRGAQ NAKAAGFDGV ELHGANGYLI 180

[0522] DQFLQSGTNH RTDAYGGPVE NRARFMLEAV DAVSEVWGAD RVGMHLAPRG GYMSISDANP 240

[0523] SETFGYVATE LGKRGLAFLM SREHEGPDWL TPQLKQQFGG VYIANEGFTY ESANAAVERG 300

[0524] DCDAVGFGKL FISNPDLPAR FARQAELTAP IPETFYSHSP EGYIDYPALA 350

[0525] SEQ ID NO: 34

[0526] MPTLFDPIRI GDLDLPNRVI MAPLTRSRAV GGGRVPNALM AEYYVQRASA GLILSEATAV 60

[0527] TPQGVGYADT PGIWSEEQVA GWKHVTDAVH AAGGRIFLQL WHVGRISDPV FLDGELPVAP 120

[0528] SAIAAGGHVS LVRPKRAFVT PRALETEEIP GIVAAYRHGA ENAKAAGFDG VEVHGANGYL 180

[0529] LDQFLQDSTN QRNDAYGGSI ENRARLLLEV TDACIAVWGP ARVGVHLAPR GDAHSMGDSD 240

[0530] PAATFGYVAR ELGKRGIAFI CSREALGDNR LGPELKRAFG GTYIANEKMT KATAEHVLQA 300

[0531] GEADAVAFGQ LFIANPDLPR RLQLDAPLNA PQPETFYHPG AEGYIDYPAL A 351

[0532] SEQ ID (ID): 35

[0533] MPTLFDTLTL GDLTLKNRIV MAPLTRCRAD EGRVPNAMMA EYYAQRSSAG LILSEATSVT 60

[0534] AMGVGYPDTP GIWSDAQVQG WKLITDAVHE AGSRIFLQLW HVGRISDPSY LNGAQPVAPS 120

[0535] AVRPAGHISL VRPLKDYDEP RALTLAEIKE VVQAYRQGAI NAKAAGFDGV HIHGANGYLL 180

[0536] DQFLQDSTNL RDDEYGGSLE NRARLMLEVT DACIDVWGKD RVAMHLAPRM DAHDMGDSNR 240

[0537] TATFGYVATE LGKRGIAFIS TREHAADDSI TPLIKQLFGG PVIANEKFSK AEANQWLAEG 300

[0538] KADAVAFGIP FIANPDLPKR LELDAPLNEP RKELFYGKGP LGYTDYPTLA 350

[0539] SEQ ID (ID): 36

[0540] MATIFDPIKL GDIELKNRII MAPLTRCRAD AGRVPNALMA EYYVQRASAG LILSEATSVT 60

[0541] PMGVGYPDTP GIWSNDQVRG WSNVTKAIHG AGGKIFLQLW HVGRISHPSY LNGETPVAPS 120

[0542] AIQPKGHVSL VRPLADYPTP RALETAEIAD IVEAYRVGAE NAKAAGFDGV EIHGANGYLL 180

[0543] DQFLQSSTNQ RTDSYGGSLE NRARLLLEVT DAAIEVWGAG RVGVHLAPRA DSHDMGDENR 240

[0544] LETFSYVARE LGKRGIAFIC SREKEGDDSI GPQLKQAFGG PYIANERFTK DSANAWLAEG 300

[0545] KADAVAFGVP FIANPDLPAR LKADAPLNEA HPETFYGKGP VGYIDYPVL 349

[0546] SEQUENCE ID (ID): 37

[0547] MATIFDPIKL GDLELSNRII MAPLTRCRAD EGRVPNALMA EYYVQRASAG LILSEATSVT 60

[0548] PMGVGYPDTP GIWSNDQVRG WTNITKAVHA AGGKIVLQLW HVGRISHPLY LNGEAPVAPS 120

[0549] AIQPKGHVSL VRPLADYPTP RALETAEIAE IVEAYRTGAE NAKAAGFDGV EIHGANGYLL 180

[0550] DQFLQSSTNQ RTDNYGGSLE NRARLLLEVT DAAIDVWGAG RVGVHLAPRA DSHDMGDDNL 240

[0551] AETFTYVARE LGKRGIAFIC SREKEGADSL GPQLKEAFGG AYIANERFTK DSANAWLAEG 300

[0552] KADAVAFGVP FIANPDLPAR LKADAPLNEP RPELFYGKGP VGYIDYPTL 349

[0553] SEQ ID NO: 38

[0554] MSYMNFDPKP LGDTNIFKPI KIGNNELKHR VVMPALTRMR AIAPGNIPNT EWAEEYYRQR 60

[0555] SQYPGTLIIT EGAFPSAQS GGYDNVPGIW SPAQLEQWKK IFAKIHENKS FVWVQLWVLG 120

[0556] QAWPEVLKKE GLRYDSATDD LYMGEEEKER ALKANNPQHG ITKEEIKQYI KEYVDAAKKA 180

[0557] IDAGADGVQI HSANGYLLNQ FLDPISNNRT DEYGGSIENR ARFTLEVVDA VVDAVGAERT 240

[0558] SIRFSPYGTF GTMSGGENPG IVAQYAYVIG ELEKRARAGK RLAFIDLVEP RVTDPFLPEF 300

[0559] EKWFKEGTNE FIYSIWKGPV LRVGNYALDP DQATLDSKKP NTLIGYGRSF IANPDLVYRL 360

[0560] EKGLPLNKYD RNTFYTFTKE GYTDYPSYEE SVAKGYKKEE KKY 403

[0561] SEQ ID NO: 39

[0562] MSFVQDFKPI ALADTKLFKP IKIGNNELAH RVVMPPLTRM RATHPGNVPN KDWAVEYYDQ 60

[0563] RSKRPGTLII TEGAFPSAQS GGYDNVPGIW SPAQLEQWKK IFAKIHENKS FVWVQLWVLG 120

[0564] RQSFADTLAR DGLRYDSASD GVYMDEEQRE RAVKSNNPQH GLTKAEIKQY ISEYVDAAKK 180

[0565] SIEAGADGVE IHSANGYLLN QFLDPISNKR TDEYGGSIEN RARFVLEVVD AVTEAIGCDK 240

[0566] VGIRLSPYGT FGTMSGGSEP LIVAQFAYVL GELEKRGKAG KRLSFVHLVE PRVTNPFYTE 300

[0567] GQGEYTEGTN DFAYSVWKGP IIRAGNLALH PEVVKKMVED DRTLIGYGRF FISNPDIVDR 360

[0568] VEKGLPLNKY NRDTFYAMTA NGYLDYPTYD EAVKLGYK 398

[0569] Sequence Listing (ID): 40

[0570] MPFVKGFEPI SLRDTNLFEP IKIGNTQLAH RAVMPPLTRM RATHPGNIPN KEWAAVYYGQ 60

[0571] RAQRPGTMII TEGTFISPQA GGYDNAPGIW SDEQVAEWKN IFLAIHDCQS FAWVQLWSLG 120

[0572] WASFPDVLAR DGLRYDCASD RVYMNATLQE KAKDANNLEH SLTKDDIKQY IKDYIHAAKN 180

[0573] SIAAGADGVE IHSANGYLLN QFLDPHSNKR TDEYGGTIEN RARFTLEVVD ALIETIGPER 240

[0574] VGLRLSPYGT FNSMSGGAEP GIIAQYSYVL GELEKRAKAG KRLAFVHLVE PRVTDPSLVE 300

[0575] GEGEYSEGTN DFAYSIWKGP IIRAGNYALH PEVVREQVKD PRTLIGYGRF FISNPDLVYR 360

[0576] LEEGLPLNKY DRSTFYTMSA EGYTDYPTYE EAVDLGWNKN 400

[0577] SEQ ID NO: 41

[0578] MPFVKDFKPQ ALGDTNLFKP IKIGNNELLH RAVIPPLTRM RAQHPGNIPN RDWAVEYYAQ 60

[0579] RAQRPGTLII TEGTFPSPQS GGYDNAPGIW SEEQIKEWTK IFKAIHENKS FAWVQLWVLG 120

[0580] WAAFPDTLAR DGLRYDSASD NVYMNAEQEE KAKKANNPQH SITKDEIKQY VKEYVQAAKN 180

[0581] SIAAGADGVE IHSANGYLLN QFLDPHSNNR TDEYGGSIEN RARFTLEVVD AVVDAIGPEK 240

[0582] VGLRLSPYGV FNSMSGGAET GIVAQYAYVL GELERRAKAG KRLAFVHLVE PRVTNPFLTE 300

[0583] GEGEYNGGSN KFAYSIWKGP IIRAGNFALH PEVVREEVKD PRTLIGYGRF FISNPDLVDR 360

[0584] LEKGLPLNKY DRDTFYKMSA EGYIDYPTYE EALKLGWDKN 400

[0585] SEQ ID NO: 42

[0586] MSFVKDFKPQ ALGDTNLFKP IKIGNNELLH RAVIPPLTRM RALHPGNIPN RDWAVEYYTQ 60

[0587] RAQRPGTMII TEGAFISPQA GGYDNAPGVW SEEQMVEWTK IFNAIHEKKS FVWVQLWVLG 120

[0588] WAAFPDNLAR DGLRYDSASD NVFMDAEQEA KAKKANNPQH SLTKDEIKQY IKEYVQAAKN 180

[0589] SIAAGADGVE IHSANGYLLN QFLDPHSNTR TDEYGGSIEN RARFTLEVVD ALVEAIGHEK 240

[0590] VGLRLSPYGV FNSMSGGAET GIVAQYAYVA GELEKRAKAG KRLAFVHLVE PRVTNPFLTE 300

[0591] GEGEYEGGSN DFVYSIWKGP VIRAGNFALH PEVVREEVKD KRTLIGYGRF FISNPDLVDR 360

[0592] LEKGLPLNKY DRDTFYQMSA HGYIDYPTYE EALKLGWDKK 400

[0593] Sequence Listing (ID): 43

[0594] MTVGLEQSNL FKPITIGKNT LDQRVAFAPT TRFRAADDHT PSDLMLQYYS DRAQAPGSLL 60

[0595] ITEATFISPR AGLYPNIPGI WNEKHVQGWK KITDAVHAKG SYMACQFWFL GRVGSPELLK 120

[0596] KHGLDLISPS ALYESEESKK AAEAAGNPVR ALTEKEIKGI IYEDYKNAAI NAMEAGFDYV 180

[0597] EIHSAHGYML DQFLQPATNQ RTDNYGGSIE KRARIVLEII DLLSDTIGAE KLAIRLSPWA 240

[0598] KFQGMKAEQD TVHPITTFSY VVNELQKRAN NGKQLAYLSL VEPRVQGNLD VNTSDIVGSN 300

[0599] DFIKKLWKGA ILQSGNYTYD SPEFKLLKAD VNGDNRTMIG FSRYFTSNPD LIDRLKKGLE 360

[0600] LTPYVRSLFY ATNNYGYNTF ANYGKELQFD PKKEEKRRPV SLI 403

[0601] SEQ ID (ID): 44

[0602] MSSVKISPLK DSEAFQSIKV GNNTLQTKIV YPPTTRFRAL EDHTPSDLQL QYYGDRSTFP 60

[0603] GTLLITEATF VSPQASGYEG AAPGIWTDKH AKAWKVITDK VHANGSFVST QLIFLGRVAD 120

[0604] PAVMKTRGLN PVSASATYES DAAKEAAEAV GNPVRALTTQ EVKDLVYETY TNAAQKAMDA 180

[0605] GFDYIELHAA HGYLLDQFLQ PCTNQRTDEY GGSIENRARL ILELIDHLST IVGADKIGIR 240

[0606] ISPWATFQNM KAHKDTVHPL TTFSYLVHEL QQRADKGQGI AYISVVEPRV SGNVDVSEED 300

[0607] QAGDNEFVSK IWKGVILKAG NYSYDAPEFK TLKEDIADKR TLVGFSRYFT SNPNLVWKLR 360

[0608] DGIDLVPYDR NTFYSDNNYG YNTFSMDSEE VDKELEIKRV PSAIEAL 407

[0609] SEQ ID (ID): 45

[0610] atggaagaag tgaggaacaa gcaggtagta ttcaaggatt atatcaatgg cttccccaag 60

[0611] gaatcagaca tgcttctcaa atcttcttcc accatctgcc tcaaacttcc acaaggttct 120

[0612] aacggcgttc tcgttaagaa cctttatctc tcctgtgatc cctacatgcg tgctcgcatg 180

[0613] accaaaactg aaggcagtta ctttcctcct ttcactcctg gttcgcctat atcaggatat 240

[0614] ggagttgcaa aagtccttga ttctgggcat ccagacttaa agaaaggtga tctagtgtgg 300

[0615] ggagggactg gatgggagga atacagcatt atcgatgctc ccgagtctct attcaagatt 360

[0616] caacatactg atatgcctct ttcctattat acaggcattc tcggtatgcc cggtatgact 420

[0617] gcttatattg gtttctatga gatttgtgct ccaaagaaag gagagtatgt atttgtttca 480

[0618] gcggcttcag gtgcagttgg tcagctcgtc ggccaatttg caaagttgtc aggatgctat 540

[0619] gttgttggga gtgctggtac aaaagaaaag gttgatctcc tgaagaacaa atttggattt 600

[0620] gatgaggctt ttaactacaa agaagagcaa gatctaaatg cagctctgaa gaggtacttt 660

[0621] cctgatggca ttgatattta ctttgaaaat gttgggggaa agatgttgga ggcagtactc 720

[0622] tcaaatatga gattaaatgg tcggatttca gcttgcggaa tgatctcaca gtacaatcta 780

[0623] gagcaaccag agggggtgtg taacctgttt ttgctggtag gaaaacgttt gcgcatgcaa 840

[0624] gggttcatcg tgagtgatta ctatcactlg tatccaaagt atatggaaat ggtaatgccg 900

[0625] ttgataaaac aaggaacaat atcttacatt gaggacattg tggagggact tgagagtgca 960

[0626] cccgcggctt tggttgggct gttttctggc agaaatgtcg ggaagcaagt ggtggttgtg 1020

[0627] gctcgtgaat ga 1032

[0628] Sequence Listing (ID): 46

[0629] atggaagaag tgaagaacaa gcaggtggta ttgaaggatt acatcaatgg cttccccaag 60

[0630] gaatcagaca tgcttctcaa atcttcttcc accatctgcc tcaaacttcc acaaggttct 120

[0631] aatggccttc tcgttaaaaa cctttatctc tcttgtgatc cctacatgcg taatcgaatg 180

[0632] agcaaatctc aaggcagtta cgttgattca cttactcctg gtttgcctat aacaggatat 240

[0633] ggagtagcta aagtccttga ttctgggcat tcagacttca agaaaggtga cctagtttgg 300

[0634] ggatggactg gatgggagga atacagcatt atcgatgctc ccgagtctct attcaagatt 360

[0635] caacatactg atatgcctct ttcctattat acaggcattc ttggtatgcc tggtatgacc 420

[0636] gcttatgctg gcttctatga gatttgtgct ccaaagaaag gagagtatgt atttgtttca 480

[0637] gcggcctcag gtgcagttgg ccagctcgtt gggcagtttg caaagttgtc aggatgctat 540

[0638] gttgttggga gtgctggtac aaaagaaaag gttgatctcc tgaagaacaa atttggattt 600

[0639] gatgaggctt ttaactacaa agaagagcaa gatctaaatg cagctctgaa gaggtacttt 660

[0640] cctgatggca ttgatattta ctttgaaaat gttgggggaa agatgttgga ggcagtactc 720

[0641] TCAATATGATTAAATGGTCGGATTCAGCTTGC GGAATGATCTCACAGTACAATCTA 780

[0642] GAGCAACCAGAGGGG GTGTGTAACCTGTTTTTGCTGGTAGGAAAACGT TTGC GCATGCAA 840

[0643] GGGTTCATCGTGAGTGAT ACTATC ACTTG TATCCAAAGT ATATGGA AATGGTAATGCCG 900

[0644] TTGATAAAACAAGGAACAATATCTTACATTGAGGACATTGTGGAGGGACTTGAGAGTGCA 960

[0645] CCC GC G GCTTT G G T G G GCT G TTTTCT G G C AGAAAT G TCG G G A G C A AGT G G T G G T G T G 1020

[0646] GCTCGTGAATGA 1032

[0647] SEQUENCE ID (ID): 47

[0648] ATGGCAGAAGTG GTGGAGAGATCGCCGGAGGT AGTGA TTGTAAGAAACAAGCAGGTGATT 60

[0649] TTCAAAGATTA CGTGAATGGA TACCCGAAAGAAACTGACATGGTG GTTACTTCTGATGC A 120

[0650] ACCATCCGTTTAAAGCTACCCGAGAATGAAAGCGGCCTTATTTTAACAAAAAATCTATAT 180

[0651] TTGT CATGC G ATCCCT AC ATG AGGGGTC GC ATGAGCAAGACTTCCG AAGGAAGTTACGT A 240

[0652] CCTTCTTTTA CACCTGGTTC GCTTATATCT GGAATGGAGT CGCAAAGGTG TGGATTCA 300

[0653] ACTCACCCCG AATACAAGAA GGGCGACTTG ATATCGGGAA TCA TCAGTTGGG AAGAATAT 360

[0654] AGTTTGATCA AAAATCCC GAATT GTTTATC AAGATT CAGCATACGGATGTTCCCCTTT CG 420

[0655] TACTATACTG GGATCCTTGG TATGGCTGGC GTGACTGCTT ATGCTGGTTT TTATGAGATT 480

[0656] TGTTTCACCAA AGAAAGGTGA CACTGTGTTT GTGT CATCAGCATCCGGAGCGTTGGTCA A 540

[0657] CTTGTA GGCC AGTTTGC GAA ACTCCATGGTT GTTATGTTGTT GGAAGTGCTGG ATCCAAA 600

[0658] GAAAAGGTTG ATCTACTCAA GAACAAATTC GG GTTTGACGAGGCATTTAA CTACAAAGAA 660

[0659] GAGCACGATC TTAATTCCAC TTAAAGAGGT TTCCCTGATG GTATTGATATT TACTTT 720

[0660] GAAAACGTTC GTGGAAAGAT GCTGGATGCA GTACTATGCA ACATGAGACT TCA TGGCCGG 780

[0661] ATTGCTGTTT GTGGGATGAT CTCACAGTAT AACCTTAATG AACATCAGGG CATAAATAAT 840

[0662] ttatcttcg ttatcttgaa acgaatccga atggaaggct tcttggttac tgatcactat 900

[0663] cacttgtttc caaagttttt ggaaatggtt ttgcctctca ttcaagaagg caagataaca 960

[0664] tatgttgagg acactattga aggccttgag aatgctcctg ctgcacttgt tggcttgttt 1020

[0665] tcgggcaaaa atgttggaaa acaaattgtt gatttaactc aagagtaa 1068

[0666] SEQ ID (ID): 48

[0667] atgggagaaa tggtggagaa caagcagatt gtactgaaag actacgtaag tgggtatcct 60

[0668] aaggagagtg atatggttac acaagtttcg aagatgagct tgaatgtacc acatgggtct 120

[0669] aatgggattg tggttaagaa tctttatttg tcatgtgatc cttacatgcg ccctcgtatg 180

[0670] accaaatcag aaggtggcta tgttgactcc ttcactcctg gtcagcctat tacgggatat 240

[0671] ggggtggcga aagtgttgga ttcagggact ccaaagttca agaaaggtga cttggtttgg 300

[0672] ggatttaccg gatgggaaga gtatagcctc attacgaaaa cagatacttt gtttaagata 360

[0673] GAGCACACAG ATGTGCCTCT TTCCTACTAC ACAGGGGTGT TAGGTATGCC CGGTATGACT 420

[0674] GCTTATGCTG GTTTCTATAA GGTGGCTACC CCAAAGAAAG GAGAATATGT TTTTGTTC A 480

[0675] GCAGCATCTG GAGCAGTTGG GCAACTTGTT GGACAGTTTG CAAAGCTTTT GGGCTGCTAT 540

[0676] GTTGTGGAGT GCTGGAAGCA AAGAAAAGTT GACCTTTTGA AGAATAAATT TGGATTT 600

[0677] GACGAGGCTT TTAAC TACAAGGAAGAGGAAGACCTGGCTGCAGC ACTAAAAGGTACTTC 660

[0678] CCTGATGGCA TTGACATTTA CTTTGAAAAT GTTGGAGGAA AGATGCTTGA TGCAGTGCTT 720

[0679] GTTAACATGA GGCCCCATGG ACGCATTGCT GTGTGTGGGA TGATCTCTCA GTACAACCTT 780

[0680] GAAAAGCCTG AAGGGCATAT ACAATTTAAC GTACGTTATT ATGAAGCAAC TCCGCA TAGAA 840

[0681] GGCTTTTTAG TATTTC ACTACTACCATCTTTATCCC AAAC TTCTGGAGTT GGTTC TGC C A 900

[0682] TATATAAAGG AAGGGAAGAT AAATTACGTG GAAGACATAG CTGAAGGCCT GGAGAGTGCT 960

[0683] ccagccgctc tcgttggact tttctctggt cgtaacgttg gtaagcaagt ggtggccgtt 1020

[0684] gctcgtgaat ga 1032

[0685] Sequence Listing (ID): 49

[0686] atggcgagtg gtggagaaat gcaagttagc aacaaacagg tgatattcag agactatgtg 60

[0687] accggcttcc cgaaagaatc tgacatggaa ttgaccacta ggagcatcac actgaagctc 120

[0688] ccacaaggtt ccactgggct tctcctcaag aacctctact tgtcctgcga tccttatatg 180

[0689] cgagcccgta tgaccaacca ccataggctc tcttatgtcg actccttcaa gcccggttcg 240

[0690] ccaataatcg gttatggagt ggctagagta ttggaatctg ggaatccaaa atttaatcca 300

[0691] ggagacttgg tttggggatt tactggttgg gaggaatata gtgtcataac tgcaacagag 360

[0692] tctctcttca agattcacaa cactgatgtg cctctctctt actatactgg acttctcggt 420

[0693] atgcctggga tgactgctta tgctggtttt tatgagatct gctctcctaa aaaaggagag 480

[0694] acggtctacg tttcagcagc atctggagca gtaggtcagc ttgttggcca atttgcaaag 540

[0695] ttgactggtt gctatgttgt tgggagtgcc ggaagcaagg aaaaggttga tttgctgaag 600

[0696] aacaaatttg ggtttgatga ggctttcaat tataaagaag aagctgacct ggatgctgct 660

[0697] ctaaggaggt acttccctga tggtattgac atctactttg aaaatgttgg ggggaaaatg 720

[0698] ctggatgcgg tgctgccaaa catgaggcct aaaggccgaa tagcagtttg tgggatgatc 780 [[ID= / /

[0699] tcacagtaca accttgagca gcctgaaggc gtccgtaatt tgatggctct gatcgttaag 840

[0700] caggtccgca tggaaggttt catggttttc tcttactatc atctttacgg aaagtttctt 900

[0701] gaaaccgtgc tgccttacat aaaacaaggc aagattacgt acgtggaaga tgtagttgac 960

[0702] ggccttgaca atgctccagc ggctctcatt ggcctctatt ctggccgcaa tgtgggcaag 1020

[0703] caggtggtgg ttgtttccag agagtga 1047

[0704] Sequence number (ID): 50

[0705] ]atgacggcga cgaacaagca agtcatattg aaagactacg tgagtggttt ccctacggaa 60

[0706] tccgatttcg atttcactac caccaccgtc gaacttaggg ttccggaagg tactaactct 120

[0707] gttctagtga agaatctcta cttgtcatgc gatccttaca tgagaattcg catggggaaa 180

[0708] cctgatcctt ccactgctgc tcttgctcaa gcttacactc ccggccagcc aatccaaggg 240

[0709] tatggagtgt ctagaataat agaatctgga catccagatt acaagaaagg agacttactc 300

[0710] tggggtatag ttgcatggga ggagtacagt gttatcactc caatgactca cgcgcatttc 360

[0711] aagatccaac atactgatgt tccattatct tattacactg gacttttagg tatgcctggt 420

[0712] atgactgcct atgctgggtt ttatgaagtt tgttctccaa aggaaggaga gacagtttat 480

[0713] gtgtcagctg catctggtgc tgttggtcag cttgtgggac aacttgctaa gatgatgggc 540

[0714] tgttatgttg ttggaagcgc tggaagtaaa gagaaggttg atcttctgaa gaccaagttt 600

[0715] gggtttgatg atgcatttaa ctacaaggaa gaatctgacc ttactgctgc cctaaaaagg 660

[0716] tgtttcccta atggcattga catatacttt gagaatgtag gaggcaaaat gctagatgca 720

[0717] gtgcttgtga acatgaacat gcacgggcgt atcgctgtct gtggaatgat ctcacagtac 780

[0718] aatcttgaga accaggaagg tgtacacaac ctatccaaca taatctacaa aagaatccgc 840

[0719] attcaaggct ttgtagtgtc tgatttctac gacaaatact caaagttctt ggagtttgtg 900

[0720] cttccccaca ttagagaagg gaagataacg tacgtggaag atgtagctga tgggcttgag 960

[0721] aaagctcccg aagctcttgt gggactcttc catggtaaga atgttgggaa acaagttgtt 1020

[0722] gttgttgctc gtgagtga 1038

[0723] Sequence Listing (ID): 51

[0724] atggcagaag aagtgagcaa caaacaggtc attcttaaaa actatgtcac aggttaccct 60

[0725] aaggaatccg acatggaaat caagaatgtc accattaaac tcaaagttcc agaaggttct 120

[0726] aatgatgtgg ttgtgaagaa tctttactlg tcttgtgacc cttatatgcg tagccgcatg 180

[0727] aggaaaattg agggtagcta tgttgaatcc ttcgctcctg gctcccctat cacgggatat 240

[0728] ggagtggcta aagttttgga gtctggtgat ccaaaattcc aaaaaggtga cttagtttgg 300

[0729] ggaatgactg gatgggaaga gtatagtatt ataacaccta ctcagactct ctttaaaatt 360

[0730] catgacaagg atgtgcctct ttcctactac acaggaatcc tcgggatgcc tgggatgaca 420

[0731] gcttatgctg gttttcatga ggtttgctcc cccaagaagg gggaaactgt ctttgtttca 480

[0732] gctgcatctg gagcagttgg tcagctcgtt gggcaatttg caaagatgct gggttgctac 540

[0733] gttgttggta gtgctggaag caaagaaaag gttgatctgt tgaagagcaa atttgggttt 600

[0734] gacgaagctt ttaactataa agaggagcag gatttaagtg cagctttgaa gaggtacttc 660

[0735] cctgatggaa ttgacatcta ctttgagaat gtgggaggga agatgcttga tgcagttctt 720

[0736] gtgaacatga aactctatgg ccgtattgct gtgtgtggga tgatttcgca atacaacctt 780

[0737] gagcagactg aaggagtgca caacttgttt tgcctcatca caaaacgaat ccgcatggaa 840

[0738] ggatttcttg tttttgatta ctatcatctt taccccaaat atttggaaat ggtcattcct 900

[0739] caaataaagg caggcaaggt tgtttatgtg gaagatgttg cccatggcct tgaaagtgct 960

[0740] cccactgctc tagttggtct cttctctggt cgcaatattg gaaagcaagt cgtgatggtt 1020

[0741] tcgcgtgaat ga 1032

[0742] Sequence Listing (ID): 52

[0743] atggggcaac aaaagcagcg taatcgacgt tgggttctgg cctcgcgtcc acatggcgca 60

[0744] cctgttccgg agaatttccg tcttgaagaa gatgatgtcg ccacaccggg tgaaggacag 120

[0745] gtgttactgc gcacagttta tttgtccctg gacccgtata tgcgtggacg tatgagcgat 180

[0746] gagccatctt attcaccgcc tgttgatatt ggcggcgtga tggtcggcgg tacggtgagc 240

[0747] cgtgtcgtgg agtcgaatca tcctgattat cagtctggcg actgggtgct gggctacagt

[0748] ggatggcaag actatgacat atccagtggt gatgatctgg tgaaacttgg cgatcatccg

[0749] caaaatccat cgtggtcgct gggtgtgcta gggatgccag gctttaccgc ttatatgggc 420

[0750] ctactggata tcggtcagcc taaagagggc gaaacgttgg tggtagctgc ggcgacagga 480

[0751] ccagtggggg cgacggtggg gcaaatcggc aaacttaaag gttgcagagt ggtgggggta 540

[0752] gccggtggcg cggaaaaatg ccgccatgct accgaggtgt taggcttcga tgtttgtctt 600

[0753] gatcaccacg cggatgattt tgccgaacaa ctggcgaaag cgtgcccaaa aggtattgat

[0754] atctattatg aaaacgtggg cggtaaggta ttcgatgcgg tgctaccgtt acttaataca 720

[0755] tctgcgcgca ttcccgtctg cggattagtg agcagctata acgctacaga gctaccaccc 780

[0756] 840. ggtccggatc gtttacctct gttgatggct acagtgctga aaaaacgtat tcgcttgcaa

[0757] ggttttatta tcgctcagga ttatggtcac cgcatccatg agtttcagag ggagatgggg 900

[0758] caatgggtga aagaggataa aatccactac cgcgaagaaa ttactgacgg tttagagaat 960

[0759] gcgccacaga cgtttatcgg cctgctgaag ggtaaaaact tcggcaaagt ggtgatccgc 1020

[0760] gtggcgggtg atgattaa 1038

[0761] Sequence Listing (ID): 53

[0762] atggcaccag ttacaaacgg acgaatcatc ttcaactcga tccctacggg ttttccggta 60

[0763] cctggagaga cgactatcta cgacaccacg gagaccattg atctcgacac ggcacctctc 120

[0764] gatgggggat tcctcctgaa gacactcgag ctgtcggttg acccttacat gcgcggcggg 180

[0765] atgcgtgccc ccgagaagaa gtcgtactca gcccctttca ctctaggaca accgcttcgg 240

[0766] gggtatggtg ttggtgtcgt tttgaggtct gaaaaccccc aagtgaaggc cggtgatcat 300

[0767] ctttatggat tctttgagca cacacactac tcgattcgta aagacctgac gggcctccaa 360

[0768] gccatcgaga atgcgtacaa ccttccctgg tcggtgttta ttggtgttat aggaatgcca 420

[0769] ggcaaaacgg catatatggc ctggaaggag tacgctcatc cgaagcaggg tgaaaccgtc 480

[0770] ttcgtctcaa cgggagcagg ccctgttgga tccttcgtca ttcaactcgc caaagccgat 540

[0771] ggtctgaaag tcattgcctc tgcgggttcg gaagaaaagg tccaattcat gaaagaggtt 600

[0772] ggcgcggacg tagccttcaa ttacaagacc acaaatacgg ctgaagtgct ggagaaagag 660

[0773] ggcccaattg atatctactg ggacaacgtt ggcggcgaga cgcttgaagc tgccctgaat 720

[0774] gctgcgaacg tcaacgctcg atttattgaa tgcggcatga tctcgggcta caacagtgga 780

[0775] ggggcaccag tccgaaacat tttccatgtt atcggcaagt ccatcaccat gaccggtttc 840

[0776] atcgtcagcc ggatcgagcc caagtacagc gccgaatttt acaaggaggt acctgccaaa 900

[0777] gtggctagtg gagagctcaa atatcgcgaa catgtgtaca atggtctcga gaagctcggc 960

[0778] GACGTCACTT GGGCGGTACA AAAAGGAGAG AAC AAGGC GAAGGCTGT TGTCCATGT G GCT 1020

[0779] GATGAT TAG 1029

[0780] SEQ ID NO: 54

[0781] ATGGCATCAG TTACCAACGG TC GC GTGCTTTTCAACTCTATTCCC GAAGGCTTCCCGAG 60

[0782] CCC GGGAAGAC AGTCGTCTAT GATACATCAG AAAATATTGACCTCGACACC GTCCCCTTG 120

[0783] AACGGTGGAT TCCTCCTCAA GACTCTCGAC CTATCGATAG ACCCCTACAT GC GCGGT CGT 180

[0784] ATGC GTGC ACC AGAGAAGAAGTCGTATTC GC CCCCTTT CCTTCTCAACC AACC AATTGAC 240

[0785] GGCTATGGTG TTGGTGT CGT CCTCCGCTCT GAGCTTCCTG AAGTGAAGCT GGAGATCAT 300

[0786] CTATACGGAT TCTTCAAGCA TGTTC AATAGACGTGC ACACGAAC TTGG AAGGCTTGA GC 360

[0787] AAACTCCCTA ACGAGCACGG CTCTCATGGA GTGTGTACG TCGGTGCTGC TG GTATGCCC 420

[0788] GGCAAGACTG CCTATATGGC GTGGAAGGAA TACTCGC AAGCGAAGAAGGGGGAGACTGT C 480

[0789] TTCGTTAGCG CCGGTGCTGG TCCTGTTGGG TCAC TTGT CATCC AATT CGCGAAAGCTGAC 540

[0790] ggcctcaagg tcattggttc tgctggatct gatgagaaag tccagttcat gaaggagtgt 600

[0791] ggcgctgacg tcgccttcaa ctacaaaact accaatacga aggaggtcct tgagaaggaa 660

[0792] ggccccattg acatcttctg ggataatgtc ggcggtgaga cccttgaagc agcactcgaa 720

[0793] gctgcgaacg tcaatgcacg attcatcgaa tgcggcatga tctctgggta taacagtgga 780

[0794] ggcgcaccca tccgcaacct gttccatgtc gtcagcaagt ccatctccat gcacggcttc 840

[0795] atcgtcagcc gtcttgagcc caaatacggg aaggagttct acgagaccat cccacacaag 900

[0796] ttggcgagcg gagaactcaa gcatcgtgaa catgtgtttg acgggcttga taaagtcgga 960

[0797] gaagcgctcc ttgcggtgca gaagggtacg aataaggcga aggcggttgt taaggtagca 1020

[0798] gacgagtag 1029

[0799] SEQUENCE ID (ID): 55

[0800] atgaatccta agtataagcc actttttgaa ccatttacgt ttaaaagcgg cgttacaatc 60

[0801] aacaaccgga tcgcagtagc accgatgact cattacgctt ctaatgaaga cggtacaata 120

[0802] tctgaagcgg agctcgacta catcatcccc cgttcaaaag agatgggaat ggtgattaca 180

[0803] gcctgcgcaa atgttacacc ggacggaaaa gcattccccg ggcagccggc catccatgac 240

[0804] gattccaaca ttccaggttt aaaaaagtta gcacaagcca ttcaggcaca aggcgctaaa 300

[0805] gctgttgtac aaattcatca cggcggtatt gagtgcccgt ctgagctcgt tcctcaacag 360

[0806] gatgttgtgg ggccaagtga cgtgtttgat aacggcaaac aaattgctcg cgcattaaca 420

[0807] gaagaagaag tggaaaacat tgtgaaggcg tttggagaag cgacaagacg cgccattgaa 480

[0808] gccggctttg acggtgtcga aattcacggt gcaaacggct acttaattca gcagttttat 540

[0809] tctccgaaaa ccaaccagcg cacggatcgc tggggaggaa gcgatgaaaa acgattagcc 600

[0810] ttcccgctcg ctattgtcga tgaagtgaaa aaagccgctt cagaacatgc gaagggtgca 660

[0811] ttcttagtcg gctaccgcct gtctccggaa gaacctgaga caccgggatt gacaatgact 720

[0812] gaaacttata cgcttgttga tgctttaggg gataaagaat tggattatct tcatatctca 780

[0813] ctgatggacg tgaactcaaa agcgcgccgc ggtgcagatc cgactcgcac acgcatggac 840

[0814] ttattgaatg aacgtgtcgg aaacaaagtg ccgctgatcg ccgtcggttc catccattcc 900

[0815] gctgatgacg cgcttgccgt catcgaaaac ggtattccac tggtcgctat gggacgcgaa 960

[0816] attctagttg accctaactg gacggtaaaa gtaaaagaag gccgtgaaaa gcaaatcgaa 1020

[0817] acagtgatca aaggcacaga taaagaaaaa tatcatttgc ctgaaccgct atggcaagca 1080

[0818] attgtgaaca cacaaggctg ggtgccttat aaagattaa 1119

[0819] Sequence Listing (ID): 56

[0820] atgaatccga aatataatcc tttatttgaa gcttttaccc tgccatccgg tgttacattg 60

[0821] aagaaccgca ttacgatggc ccctatgact aactttgctt cccacgaaaa tggcgaagtc 120

[0822] agtgacgagg aactggcata ctaccgtgag cgctccggtg gtgtgggagc ggttattacc 180

[0823] gcttgtgtgt atgtaactcc agatggtaaa ggatttgtta atgagtttag tgcggacaag 240

[0824] gatgagatga ttcctagcct acgtcgtctg gcagatacga ttcatcagga gggcgcgaaa 300

[0825] gcgatcctgc aaatttatca tggtggccgt ctgtgtccgc cggatcaaat tccagacgga 360

[0826] caaccaatta gtgcaagcgc agtagccgag gaaaaagaag gcgcacctgt gccgcgtgaa 420

[0827] atgacatctg acgatatcca ccgcgtcatc cgtgcctatg gcgaagctac tcgccgcgcg 480

[0828] attgaagcag gctatgatgg tgtagagctt cacggagcga atggttacct ggttcagcag 540

[0829] ttcttctctc cgcattccaa cattcgtacg gatgaatggg gaggaagcct tgaagaacgg 600

[0830] ttgacttttc cgctggcggt tgttcacgaa gtgaagaaag tgatcgcaga acatgcgaag 660

[0831] cgtccgttca tcttcggata ccgcttgtct cctgaggaag gacacacgcc aggcatcacg 720

[0832] ctggatgata cgatggtgct tgtagaccgc ctggcagatg aagggctgga ttacctgcac 780

[0833] atttccgtaa atcatttctt cggcggttcg ttccgtgacc gtagtgacga acggtcacgt 840

[0834] acggttctca tccatgagaa ggttgggaac cgtgtgccag tcatgggagt tggttcactg 900

[0835] aatactccgg atgaggcgct tgcagcactg gagacaggtg taccgcttgt ttcactggga 960

[0836] cgtccgttgt tgatggagcc gcaatgggtt cagaaggtgc aaaacggcac tgaagatact 1020

[0837] attcgcacga cattatccaa gcaagcccaa caggagctgg tcattcctga ctatttgtgg 1080

[0838] ggtgcactga cgaccatccc tggctggatg ccggttacgg actga 1125

[0839] Sequence Listing (ID): 57

[0840] atgaacacag aattactgtt taaacctttt aaggcaggta atttatctct tcccaatcgg 60

[0841] attgttatgg cgcctatgac acggaatttt tctcctcaag gtattccagg gcctgaagtg 120

[0842] gccgcgtatt atcgtcgccg tgcggaaaat gcagttggat tgattattac ggagggcact 180

[0843] gctattaatc atcctgcagc tgtggagcac acaagcattc ctaattttta tggagaggga 240

[0844] ttagagggat gggccaaggt agttgaggag gttcatgcgg taggtggcaa gattataccg 300

[0845] cagctctggc atgtgggtac ggcccgtaaa ataggtgcag ataatcaacc gaatcccgag 360

[0846] gcattgcctg tcggtccgtc cggtatttct cccgctggtg aaaaggtagt cgagccattg 420

[0847] acggaggctg agattgcgga tattatctcc gcttatgctc aggccgctgc cgatgcccag 480

[0848] cgagtggggt ttgacggtat tgagcttcat ggagcacacg gctatttaat cgatcaattt 540

[0849] ttctgggaca aaacgaataa gcgtaccgat caatacggag gcaatttggt ccagcgtact 600

[0850] cggtttgcgg tggaggtcat tgaggcttgc cgtcgtgcag tggggccgaa cttcccaatt 660

[0851] gtactgcgat tctcccagtg gaagatgtat cactatgaag aaaagctggc acagacacca 720

[0852] caggaacttg aacagtttct cactccatta gtgaaggccg gggtggatat attccattgc 780

[0853] tcaagccgcc gtttttggga accggaattt gaagggtctg atctaaattt ggcagcttgg 840

[0854] accaaaaaga taacaggcaa gccagtgatt actgtgggct cgattggttt ggagaaggcc 900

[0855] tttttgagtg atttggaaaa aaataataat cgtcaaaccg atcaatccag tagtgtagag 960

[0856] gcaagattag aacaactcgt ggggcaagta gaacgagagg aagctgatct ggttgcggtt 1020

[0857] gggcgtgctt tgttggttga tccagcgttt gcggtgaagt tacgtgatca acaaatagaa 1080

[0858] gaaattattc cttacagtga tgaagtatta aaaacgttga attga 1125

[0859] Sequence number (ID): 58

[0860] atgaacacga tgctgttttc gccgtataca atccgcgggc tgacgctgaa aaaccgaatt 60

[0861] gtcatgtcgc cgatgtgcat gtattcgtgc gacacgaaag acggcgccgt acgcacgtgg 120

[0862] cataaaatcc actacccggc tcgcgctgtc ggccaagtcg gcttgattat cgttgaagcg 180

[0863] accggcgtga cgccgcaagg tcgcatttct gaacgcgact taggcatttg gagcgatgac 240

[0864] catatcgccg ggcttcgcga actcgttggg cttgtgaaag agcatggggc ggccatcggc 300

[0865] atccagcttg cccatgcggg gagaaaatcg caagtgccgg gagagatcat cgctccgtca 360

[0866] gccgtcccgt ttgatgattc gtcgccgacg ccaaaagaaa tgacgaaagc cgacattgaa 420

[0867] gaaacggtgc aagcgttcca aaacggcgca cggcgcgcga aggaagccgg ctttgacgtc 480

[0868] attgaaatcc atgccgccca cggctacctc attaacgaat ttttatcgcc gctctccaac 540

[0869] cggcgccaag acgagtacgg cggctctccg gaaaaccgtt accgtttctt gggcgaggtg 600

[0870] atcgacgctg tccgcgaggt gtgggacgga ccgctttttg tccgcatctc ggcgtccgac 660

[0871] taccatccgg acgggctgac ggccaaagac tatgtcccat acgccaagcg gatgaaagaa 720

[0872] caaggagtcg acctcgtcga tgtcagctcc ggcgctattg ttccggcgcg catgaacgtc 780

[0873] tatcccggct accaagtgcc atttgccgaa ctgatccgcc gtgaagcaga catcccgacc 840

[0874] GGCGCTGTCG GCCATTACGT CCAGCTGGCA AGCGGAAGAA ATTTGC AAAACGGCCGC 900

[0875] GCCGATCTCG TCTTTTTGGG GCACGAGCTG CTGCGCAACC CTTATTGGCC ATACGCCGCG 960

[0876] GCGAGAGAGC TGGGCGCAAA AATCTCGGCG CCCGTCCAAT ATGAGCGCGG CTGGCGGTTC 1020

[0877] TAA 1023

[0878] SEQ ID NO: 59

[0879] ATGACCGGCA AACTCTTTTC CCCGATTTCC GTCGGCCCgc tgtccctgcc caaccgcatc 60

[0880] TTCATGGCGC CGCTGACGCG CATGCgcagc cgtgagcccg gtgatgtgcc ggtgctgccg 120

[0881] CTGATGGCCG AATACTATCG CCAGCGCCAA TGCggggctg atcatcagcg aggctacg 180

[0882] CAAGTGTcGC CGCAGGGCAA GGGCTACATG GGCACGCCGG GCATCCACAG CGCCGAACAG 240

[0883] GTTGAGGCCT GGCgggACAT CACCCGCGCC GTGCACGATG AGGGCGGcca TATCGCCATC 300

[0884] CAGTTGTGGC ATGTCGGCCG GGTTCGCACC ACTCGCTGCA ACCGGACCgg CAATTGCCG 360

[0885] GTGTCCGCTT Cggccatccc ctacgaaaac aagaccacca TCCGTGGCGA GGACAGCAAG 420

[0886] ccgcagcgcg tcgcctgcga cacgccccgc gcgctgcgca cagatgaaat tcccggcctg 480

[0887] atcgaaacct accgccaggc cacgattaac gcccgcgagg ccggtttcga cctggtggaa 540

[0888] gtgcacgccg cccacggcta tctgctgcac cagttccagt ccgccgtcag caaccaccgc 600

[0889] gacgacgcct acggcggctg cctggaaaac cgcgcccgcc tgacgctgga agtggtcgac 660

[0890] gcctgcatcg ccgcctggga tgccgcccac gtcggcatcc gcatctcgcc gctgggcacc 720

[0891] ttcaacgggc tggatgactc ggccggtctg gaaatgggcc tgtatctggc cgaacaactg 780

[0892] gccaagcgca acattgccta cctgcacctg tccgaaccgg actgggcggg cggcccggcg 840

[0893] cactccgacg agttccgcca ggcgctgcgc gaccgcttcc ccggcgtcat catcggcgcg 900

[0894] ggcaactaca cggtggaaaa ggcggaggcc ttgctggcca agggctacat cgatgccgcc 960

[0895] gccttcggtc gcccctatat cagcaatccc gacctggccg agcgtttccg caccggtgcg 1020

[0896] gccttcggtc gcccctatat cagcaatccc gacctggccg agcgtttccg caccggtgcg 1020GCGCTGGCGA TGCTGAATCC GGCCACGCTC TATGGCGGCG GCGAGGAAGG TTACACC GAC 1080

[0897] TACCCGGCGC TGGCCTGA 1098

[0898] SEQ ID (ID): 60

[0899] ATGTCCGGCA AACTTTTTAC CCCGGTAACC ATTGGTGGTT TTACCCTGCC CAATCGC GTG 60

[0900] CTCATGGCAC CGCTGACGCG CATGC GCTCC AGTC AGCCGGGTG ATGTACC CAATGA ACTG 120

[0901] ATGCAGGCCT ATTACGTGCA GC GC CAGC GCCGGGATG ATCATTGCAG AGGCCACGC AG 180

[0902] ATTT CGCCAC AGGGCAAGGG TTACATGGAT ACCCCGGTAT TTACAGTGC CGAACAGGTG 240

[0903] GC GGGCTGGAA GAAGATCAC GCAGGC CGTG CATGAGGC C ACGGCCATAT CTGCCTGC AG 300

[0904] CTCTGGCATG TC GGCCTGTCT CGCATCACTC GCTGCAGCCG GACCAGCAGT TGCCGGTA 360

[0905] TCGGCCTCTG CCATACCCTA TGA AAACC GCACGACAGT GC GTGGTGA GGA TGGC AAGGTC 420

[0906] AAGCGTGTGG CCTGTGATAC TCCACGTGCA CTGGAGCTGA CCGAAATTC CCGGACTGATC 480

[0907] GAGGACTACC GACGTGCGAC AGTGAATGCG CGCGAGGCCG GTTTCGACAT GGTTGAAGTG 540

[0908] CATGCCGCCC ATGGCTATCT GCTGCACCAA TTCAGTCGGC CACCAGTAAC CAGCGTAAT 600

[0909] GACGCTTACG GCGGCTCACT GGAGAACCGT GCgcGGCTGA CACTGGAGGT GCTGGATGCC 660

[0910] GTGATTGGTG CATGGGATGC AGCGCATGTC GGcatCCGCA TCTCGCCGCT GGGCATTttC 720

[0911] AACGGCCTCG ATGATCGTGA CGGCCTGGAC ATGGGGCTGT ATCTGGCCGA GCAGTTTGCC 780

[0912] CTGCGGGGGA TTGGGTACCT GCACCTGTCC GAGCCGGACT GGGCCGgtGG TCCGgtACTT 840

[0913] AACGAGGAAT TCCGTGTCGC CCTGCgtGCC CGCTTCCCCG GcatCATCAT TGCggCAGGC 900

[0914] AActATTcGG TGGAAAAGGC CGAAGGATtg CTGGAGAAGG CTtgATTGA tgCTGCggCA 960

[0915] TTcGGTCGAC CGTTCATTGC CAATCCGGAT TTGCCGCAGC GCTTgcGCAa GGGTGCCGAG 1020

[0916] CTCAACGCGT CAATGCAGCG ACCCTCTATG GTGGCGGTGC AGAAGGCTAt ACggATTAt 1080

[0917] CCTGCgtTGG CCTGA 1095

[0918] SEQ ID NO: 61

[0919] atgtccggca agttgttcac cccgttcagc tcgggttcct tcaccttccc caaccgcgtt 60

[0920] atcatggcgc cgctgacgcg tatgcgcgct tcgcagccgg gtgacattcc caacgagctg 120

[0921] atgcagacct attacgtgca gcgcgccagc gccggcctca tcatcgccga ggccacgcag 180

[0922] atctccccgc agggcaaggg ctatatggac actccgggga tttattccgc ggagcaggtg 240

[0923] cagggctggc gcaagatcac ccaggccgtg catgaggccg gtggccatat cgccctgcag 300

[0924] ctctggcatg tgggtcgtgt ttcgcatcac agcctgcagc ccgaccagca actgccggtg 360

[0925] tccgcttctg ccattcccta ccagaaccgc accacggtcc gtggtgaaga cggcaagccc 420

[0926] acgcgcgtgg attgcgatac cccacgtgcg ctggaactgt ccgaaatccc cggtgtgatc 480

[0927] gaagactacc gccgcgccac cgtgaattcg cgcgaagccg gtttcgacat ggtggaagtg 540

[0928] catgccgcgc atggctatct gctgcaccag ttccagtccg ccgaaagcaa caagcgtgaa 600

[0929] gacgcctatg gtggttcgct ggaaaaccgt gcccgcctga cgctggaagc cctggatgcc 660

[0930] gtgatcggtg cctgggatgc caagcatgta ggtatccgca tttccccgct gggcaccttc 720

[0931] aacggcctgg acgacaagga cggcctggaa atggcgctgt atctcacgcg tgaattcacc 780

[0932] aagcgcggta tcgcctacct gcatctgtcc gagccggact gggccggcgg tccggcgcat 840

[0933] ggcgacgaat tccgccaggc cctgcgcgac gctttcccgg gcaccatcat cggtgccggc 900

[0934] aactacacgg tggaaaaatc ggagatgctg ctggccaagg gctttatcga tgccgccgcg 960

[0935] tttggtcgtc cctttattgc caatccggac ctgccggtgc gtctgcagaa gggcgctgag 1020

[0936] ttgaacaatg tggtggcggc tacgctgtat ggcggtggcg ccgaaggcta tacggattat 1080

[0937] ccggcgctgg cctga 1095

[0938] Sequence Listing (ID): 62

[0939] atgaaactct tgcaaccgct gcaaatcggc cccctcaccc tgcccaaccg tgtcttcatg 60

[0940] GCGCCCCTCA CCCGCCTGCG CAGCCTGGAG CCGGGCGATG TACCCACcac gctgatgggc 120

[0941] GAGTACTACC GTCAGCGCGC CAGTGCGGGC CTGATCATCA CTGAAGCCAC GCAGATCTCC 180

[0942] TTCCAGGCCA AGGGCTATTC TGGCTCGCCC GGCATTACAT AGCCGGAACA GATCGCTGCC 240

[0943] TGGAAGCACA TCAACGAAGG CATTCA CGCC GATGGCGGCC ACAGCGCCGT GCAGGTCTGG 300

[0944] CACACCGGGC GGGTGTCACA CACTTCTCTG CAACCTGGCG GC GAAGCGCC AGTGGCCCCT 360

[0945] TCGGC ACTTC CGGCAGGTGC GC GC ACTACC CTGC GTGACG AGCAAGGCGA CCTGATACGC 420

[0946] GTA GAAACAT CC GC GCCGC GGGCGCTC AGCGAAGCGG AAA TTGCCGGTA TTGT CGCCGAC 480

[0947] TTCGGCCTGG CC GCGATCAAC G CCCGTGAAGC CCGGTT CGACTT CATCGAGCTGC TGC G 540

[0948] GCCC ATG GTTACCTGCTGC ACCAGTTCCTTACCCCAAGTG CCAACCAGCGC GAAGACC GT 600

[0949] TACGGCGGCA GC GTCGAAAA CC GC GCACGT ATTGTGCTGG AGGC GGTGGACGC GGCCGTT 660

[0950] gccaactgga gcgccgagcg cgtcggcatc cgcgtgttcc cgttgggtgg tttcaatggc 720

[0951] gtggacaatg gcgaagacca ggaagccgcc ggcctgtatc tgatccgcga gctggccaag 780

[0952] cgcaacctcg cctacctgca cctctccgag cctgactggg ccggtggcaa gccattgcgt 840

[0953] gacgaattcc gccaggcaat ccgcgcggct tacccgggcg taatcatcgc ggccggtgct 900

[0954] tacaccgccg agaaaggcga agacctgatc gggcgtggcc tgatcgatgc cgtggcgttc 960

[0955] gggcgcagtt acatcgccaa cccggacctg gtcgagcggc tgcggctcca ggcgccgttg 1020

[0956] aacgagcacc gggcgcagtt cgactatgcc aatgggcctg aagggtatac ggattatccg 1080

[0957] ttcctgaagc aggcttag 1098

[0958] Sequence number (ID): 63

[0959] atgtcatctg aaaaactgta ttccccactg aaagtgggcg cgatcacggc ggcaaaccgt 60

[0960] atttttatgg caccgctgac gcgtctgcgc agtattgaac cgggtgacat tcctaccccg 120

[0961] ttgatggcgg aatactatcg ccaacgtgcc agtgccggtt tgattattag tgaagccacg 180

[0962] caaatttctg cccaggcaaa aggatatgca ggtgcgcctg gcatccatag tccggagcaa 240

[0963] attgccgcat ggaaaaaaat caccgctggc gttcatgctg aaaatggtca tatggccgtg 300

[0964] cagctgtggc acaccggacg catttctcac gccagcctgc aacctggcgg tcaggcaccg 360

[0965] gtagcgcctt cagcacttag cgcgggaaca cgtacttctc tgcgcgatga aaatggtcag 420

[0966] gcgatccgtg ttgaaacatc catgccgcgt gcgcttgaac tggaagagat tccaggtatc 480

[0967] gtcaatgatt tccgtcaggc cattgctaac gcgcgtgaag ccggttttga tctggtagag 540

[0968] ctccactctg ctcacggtta tttgctgcat cagttccttt ctccttcttc aaaccatcgt 600

[0969] accgatcagt acggcggcag cgtggaaaat cgcgcacgtt tggtactgga agtggtcgat 660

[0970] gccgggattg aagaatgggg tgccgatcgc attggcattc gcgtttcacc aatcggtact 720

[0971] ttgatggcgg aatactatcg ccaacgtgcc agtgccggtt tgattattag tgaagccacg 180ttccagaaca cagataacgg cccgaatgaa gaagccgatg cactgtatct gattgaacaa 780

[0972] ctgggtaaac gcggcattgc ttatctgcat atgtcagaac cagattgggc ggggggtgaa 840

[0973] ccgtatactg atgcgttccg cgaaaaagta cgcgcccgtt tccacggtcc gattatcggc 900

[0974] gcaggtgcat acacagtaga aaaagctgaa acgctgatcg gcaaagggtt aattgatgcg 960

[0975] gtggcatttg gtcgtgactg gattgcgaac ccggatctgg tcgcccgctt gcagcgcaaa 1020

[0976] gctgagctta acccacagcg tgccgaaagt ttctacggtg gcggcgcgga aggctatacc 1080

[0977] gattacccga cgttgtaa 1098

[0978] Sequence Listing (ID): 64

[0979] atgtccgctg aaaagctgtt taccccactg aaagtgggtg ccgttactgc cccaaaccgc 60

[0980] gtgtttatgg ccccacttac ccgtctgcgc agcatcgagc cgggcgatat cccaacgcca 120

[0981] ttgatgggtg agtattaccg ccagcgcgcc agcgcgggcc tgattatctc cgaagccacg 180

[0982] cagatttctg ctcaggcaaa aggctacgcc ggtgcaccgg gtctgcacag cccggaacag 240

[0983] atcgccgcgt ggaaaaaaat caccgcaggc gtgcatgctg aagatggccg tattgcggtt 300

[0984] cagctgtggc acaccggtcg tatctcacac agcagcatcc agcctggcgg tcaggcgccg 360

[0985] gtttctgcct ctgccctgaa cgccaatacc cgcacttccc tgcgcgatga aaacggtaat 420

[0986] gcgatccgcg tcgacaccac cacgccacgc gcgctggagc tggacgagat cccgggtatc 480

[0987] gtgaatgatt tccgtcaggc cgtcgccaac gcccgggaag cgggcttcga cctggttgag 540

[0988] cttcactctg cgcacggtta cctgctgcat cagttcctgt ccccgtcttc caaccagcgt 600

[0989] accgaccagt acggcggcag cgttgaaaac cgcgcgcgtc tggtgcttga agtggtggat 660

[0990] gctgtctgta atgagtggag cgcagaccgc attggtattc gtgtctcccc gatcggtact 720

[0991] ttccagaacg tcgacaacgg tccgaacgaa gaagcagacg cgctgtatct gattgaagag 780

[0992] ctggcgaaac gcggtatcgc ctatctgcac atgtccgaga cggacttggc aggcggcaag 840

[0993] ccttacagtg aagccttccg tcagaaagtg cgcgagcgct tccacggcgt gattatcggg 900

[0994] gcgggtgcgt atacggcaga aaaagccgag gatttgatcg gtaaaggcct gatcgacgcc 960

[0995] gtggcctttg gccgtgacta cattgctaac ccggatctgg ttgcccgttt gcagaaaaaa 1020

[0996] gccgaactga acccgcagcg tcctgaaagc ttctatggcg gcggcgcgga aggttatacc 1080

[0997] gactaccctt cactgtaa 1098

[0998] Sequence number (ID): 65

[0999] atgaagactg ctaaactgtt ctctcctttg aaggttggcg cgctcacttt gccaaaccgc 60

[1000] gtatttatgg caccactgac tcgcttacgc agtattgagc caggtgatat cccaacccct 120

[1001] ttaatggcgg aatattatcg tcaacgggcc agtgccggtt tgattatcac cgaagcaacc 180

[1002] cagatctctt tccaggcaaa aggctacgcg ggagcaccgg ggttacacac tcaggagcag 240

[1003] ttgaacgcgt ggaaaaaaat cactcaggcg gtgcatgagg aggggggaca tattgccgtg 300

[1004] cagctgtggc atgttggacg catttcgcac agtagcttgc agcccggcca acaagcgcca 360

[1005] gtagcgcctt cagctattgc cgctgatacc cgcaccaccg tgcgcgatga aaacggtgcc 420

[1006] tgggtgcgcg ttccctgctc caccccgcgc gccttggaaa cagaagagat cccgggcatc 480

[1007] attaatgatt tccgtcaggc caccgccaat gcgcgcgaag cgggttttga ctatatcgaa 540

[1008] ctccatgccg cccatggtta tttgctgcat caatttatgt ctccggcctc aaatcagcgt 600

[1009] accgaccaat acggtggtag cattgaaaac cgtacccgtc tgacactgga ggtggttgac 660

[1010] gccaccgctg cccaatggag tgctgaacgt attggtatcc gtatctcccc attagggccg 720

[1011] ttcaatggtc tggataatgg tgaagatcag gaagaagcgg cactgtatct gattgatgaa 780

[1012] ttgaacaaac ggcatatcgc ctacctgcac atctccgagc cagattgggc cggtggtaaa 840

[1013] ttgaacaaac ggcatatcgc ctacctgcac atctccgagc cagattgggc cggtggtaaa 840ccttactcag aggcgttccg tgatgcggtt cgtgcgcgct tcaaaggggt tattatcggt 900

[1014] gcgggtgcct ataccgccga gaaggccgaa gagttgattg agaaaggctt tattgatgcg 960

[1015] gtagcttttg gtcgcagcta tatctctaac ccagatttag tcgctcgcct acaacagcat 1020

[1016] gccccactga atgagcctga tggcgaaaca ttctacggcg gcggtgctaa gggctacact 1080

[1017] gattacccaa cgctgtga 1098

[1018] Sequence number (ID): 66

[1019] atgaagacag caaaattgtt ctctcccctg aaagtcggtg catttacgct acctaaccgc 60

[1020] gtatttatgg ctcctctgac tcgcttacgc agcattgagc caggagatat tcctacacca 120

[1021] ttaatggccg aatattatgc ccagcgcgcc agcgccggtt tgatcatcac cgaagcgacg 180

[1022] caggtttctt ttcaggccaa aggctacgcc ggtgctccgg gtttacacac tcaggaacag 240

[1023] ttggaaggat ggaaaaaaat cactcaagcg gtacatgaaa aacaaggaca tatcgccgta 300

[1024] caactttggc atgtcggtcg tatttctcac catagtttgc agccaaacca acaggctccg 360

[1025] gtagcccctt cggccattgc cgccgacacc cgcaccacca ttcgtgatga aaatggtgat 420

[1026] tgggttcgtg ttccttgctc tacaccacgc gcgctggaat tacaggaaat cccagcgatt 480

[1027] gttgatgatt ttaggaacgc gacggccaat gcccgcgaag ccggttttga tttcattgaa 540

[1028] atccatgcgg cacacggcta tttattacac caattcatgt ctccggcatc caaccagcgc 600

[1029] accgatgctt acggcggtag cattgaaaac cgcactcgcc tgacgttgga agtggttgat 660

[1030] gcgaccgccg cagaatgggg cgcggaacac attggtatcc gtatttcacc acttggccca 720

[1031] ttcaatggcc tggataacgg tgaagatcag gaagatgcgg cgctgtatct gattgatgaa 780

[1032] ctcaacaaac gtaaaattgc ttatttacat atctctgagc cagattgggc gggtggaaaa 840

[1033] ccttacaccg acgctttccg cgatgccgta cgggcgcgct tcaatggcat tatcgtcgga 900

[1034] gccggtgcct atacggccga aaaagccgaa accctgattg aaaaaggctt tattgatgcg 960

[1035] gttgcctttg gccgcagcta tattgccaac ccagatctgg tcgaacgcct gcaacaacaa 1020

[1036] gcgccactga atacaccaga cggcgacacg ttctatggtg gtggagcaaa aggctatacc 1080

[1037] gactacccga ctttatcgtg a 1101

[1038] Sequence Listing (ID): 67

[1039] atgacctcgc tcttcgaccc cctcaagatc ggcgacatcc agcttgccaa ccgcatcgtc 60

[1040] atggcgccgc tgacgcgcaa ccgctccccg ggtgcggtac cgaacacgct gaacgcggcc 120

[1041] tattacgagc agcgcgcctc ggccggcctc ctgatcaccg aagcaaccgc catctcccac 180

[1042] cagggccagg gctatgccga cgtgccgggc ctctacaagc cggaagccct tgaaggctgg 240

[1043] aagcaggtca ccgatgccgt gcacaaggct ggcggcaaga ttgtcgtgca gatgtggcat 300

[1044] gtcggccgga tctcgcatga cacgctgcag ccgaacggcg gcaagccggt cgccccgtcg 360

[1045] GCGATCCGCG CCAAGTCGAA GACCTACCTG ATCAATGCCG ATGGCACGGG CAGCTTCGCC 420

[1046] GAGACCTCCG AGCCACGCGC GCTGGAAAAG GACGAGCTTC CGGGCATCAT CGAAGACTAT 480

[1047] CGCCGTGCCG CCCGCGCCGC Cgtggatgcc ggtttcgatg gcgtcgaaat ccacgccgcc 540

[1048] AACGGCTACC TGCTCGACCA GTTCCTGCgt tccggcagca acgagcgtac cgacgaatat 600

[1049] GGCggctcga tcgaaaaccg cgcccgcctg ctcttccagg tcgtcgacgt catcaccaaa 660

[1050] GAAATCGGCG CCggccgcac cgcgatccgc atctcgccgg tgacgccggc aaacgattcc 720

[1051] TCCGATCCGA ACCCgcagcc gctcttcacc tatgtcgtgg aaggcctcgc caaatacgac 780

[1052] CTCgcctata tccacatcat cgaaggcgcg accggcggtc cgcgtgatca ccagcagggc 840

[1053] GACgcgccgt tcgactatgc ggcactgcgc gcagcctatc aggctgccgg cggcaaggcg 900

[1054] GCCTGGATGG TCAATAACGG CTACAACCgc gaactcgcca tcgacgcggt ggaagaaggc 960

[1055] aaggccgacc tcgtcgcctt cggcaagctc ttcatcgcca atccggacct cgtggagcgc 1020

[1056] ctgaagaacg acaccgtgct gaacccgccg gaccaggcca ccttctacgg cggcggcgcc 1080

[1057] aagggctata cggactatcc ggccctggaa aacgtcgcct ga 1122

[1058] SEQ ID (ID): 68

[1059] atgacaaaac tgttcgaacc ggcacaggca ggcgatatcg cactggcaaa ccgcatcgtt 60

[1060] atggcacctc tcacccgcaa ccgttcaccg ggtgctattc caaacaatct gaacgctgcc 120

[1061] tattatgaac agcgcgccac tgctggcctt atcgtcacgg aaggcacgcc cgtatcgcag 180

[1062] caaggccagg gttacgccga tgttcccggc ctgtataagc aggaagccat cgatggctgg 240

[1063] aaagcggtga ccgacggcgt tcacaaggct ggcggcaaga tcgtcgcgca gatttggcac 300

[1064] gttggccgta tctcgcacac atcgcttcag ccgcatggcg gccagccggt tgctccttca 360

[1065] ccgatcaagg ccaattccaa gacctacatc atcaatgatg atggcacggg cagcttcgca 420

[1066] GAAACATCCG AGCCACGGGA AATCTCGCTG CAGGAAATCC CCgtcattct tgaggattat 480

[1067] CGCACCggcg cgcgggccgc gatcgacgcc gggttcgacg gcgtggaaat ccCatgccgcc 540

[1068] AACGGCTATC TGATCGACCA GTTTCTGAAA TCAGGCACCA ACCAGCGCAC GGACGCTTAC 600

[1069] Ggtggctcga ttgaaaaccg cgcccgcttc ctgctggaag tcgtggacac tgtgacgaag 660

[1070] GAAATCGGCG CTGGCCGCAC Cggcattcgc ctgtctcccg tcacaccggc caacgacatt 720

[1071] TTCGAAGCAG ATCCCCAGCC GTTgttcgaa tatgtcgcac gcgaactcgg CAGCCGTGGC 780

[1072] CTCGCCTTCA TCCACGTcat cgaaggcgcg acaggtggac cgcgtgattt caagcagggc 840

[1073] GACAAGCCAT TCGACTATGA Tgcgctgaaa gctgcctaca ccaatgccgg GGGCAAAGGC 900

[1074] CTGTGGATTG ccaacaacgg ctacgaccgc gaaagcgcga TTGCCGCGAC CGAAAGCGGC 960

[1075] AAGGTCGATG CGGTCGCCTT CGGCAAAGCC TTTATTTCCA ATCCGGACCT Ggtgcagcgt 1020

[1076] ctgaaggaaa atgcggctct caacgagcca aaccagcaga cattttatgg tggtggtgca 1080

[1077] gaaggctaca ccgactatcc cgctttggca taa 1113

[1078] SEQ ID NO: 69

[1079] atgtccgatc tcttcgaacc gaccaggcc ggcgacatcg cgctcgccaa ccgcatcgcc 60

[1080] atggcgccgc tcacgcgcaa ccgttccccg ggcgaggcgc cgaacgatct caacgtcacc 120

[1081] tactaccagc agcgcgccac cgcaggcctg atcattaccg agggtacgcc gatcacccat 180

[1082] cagggccagg gctatgccca tgtgccgggg ctctacaagc ccgaggcgct ggaaggctgg 240

[1083] aaaaaagtca cggatgccgt ccacaaggct ggtggcaaga tcgtcacgca gatctggcat 300

[1084] gtcggccgcg tgtcccacac ctcgctgcag cctggcgaag gcaagccggt ggcgccctcg 360

[1085] gcgatcacgg cgaagtccaa gacctatatc atcaatcccg atggcagcgg cgcgtttgcc 420

[1086] gatacctccg agccgcgagc gctctcgctt gaggagattc ccggcattct tgaggactat 480

[1087] cgcgtggccg cgcgtgcagc cgtggatgcc ggtttcgacg gtgtcgaaat ccacgccgcc 540

[1088] aatggctatc tgcttgacca gttcctgcgc tccggctcca accagcgcac cgacgcctat 600

[1089] ggcggctcga tcgagaaccg cacgcgcctg acgctggaag tcgcagccgt ggtggccaag 660

[1090] gaaatcggcg gcggtcgcac cggcatccgc atctcgcccg tcaccccggc caatgatgtc 720

[1091] ttcgaccccg agccgcagcc gctgttcaat catctggttt cgaagctcgc ggggctcgac 780

[1092] ctggccttca tccacgtcat cgaaggcgcg accggcggtc cgcgcgactt caagcagggc 840

[1093] gacaagcctt tcgattggga cgagttgcgc aagacctatc gcgacgccgg cggcaagggc 900

[1094] gcctggatgg tcaacaacgg ctatgacaag gcatccgcca ccgaagccgt tgccagtggc 960

[1095] cgggccgaca ttgtcacctt cggcaagctg ttcatcgcca atcccgacct ggtgcgccgc 1020

[1096] ttcaaggagg atgcgccgct gaacgagccg aacaaggcca ccttctatgg cggcggcgcc 1080

[1097] gaaggctata cggactatcc gttcctgccc taa 1113

[1098] Sequence Listing (ID): 70

[1099] atgccgactc ttttcgaccc cttgactttg ggcgacctgc aatctccaaa ccgtgttctg 60

[1100] atggcaccgc taacgcgtgg ccgcgcgacc cgcgagcacg tgcctaccga gctgatgatc 120

[1101] gagtattaca cccagcgtgc cagcgcgggc ctgatcatca ccgaagccac cggcatcacc 180

[1102] caagaaggcc taggctggcc ctatgcgccc ggcatttgga gcgatgaaca ggtcgaggcc 240

[1103] tggaagccgg tgacccaggc cgtgcatgag gcaggcggac ggatcattct tcagttgtgg 300

[1104] catatgggcc gtaccgttca ttccagcttt ctcggcggag ccaagccagt atcgtcctcg 360

[1105] gccacccgtg cgccgggaca ggcgcacacc tacgaaggca agcaagacta cgacgaggcg 420

[1106] cggcctttgt cggcggatga aatcccgcgg ctattgaacg attacgaaca cgcagcgaaa 480

[1107] aacgccatgg ccgcaggctt cgacggcgtg cagatccatg ctgccaatgg ttacctaatc 540

[1108] gaccagttcc tgcgcgacaa cagcaacgtt cgcggggacg cctacggggg ttcaatcgag 600

[1109] aaccgcatcc gtctattggt cgaagtcacc cggcgcgtgg cggagaccgt aggtgccgaa 660

[1110] aaaacgggcg tgcggctgtc acccaacggt gattcccaag gcgtcaacga cagcaatccg 720

[1111] gagccgctgt tcagcgccgc ggccaaggcc ttggatgaga tcggcatcgc tcatctggag 780

[1112] ttgcgcgaac cagggtatga aggcaccttc ggcaaggccg accggccgcc cgtgcacccg 840

[1113] gtcatccgcc aggcgttcag ccgtacgctg attctcaact ctgactacac tttggaaacg 900

[1114] gctcaggctg cactagccac cggagaagcg gacgcgatca ccttcggccg cccgttcctg 960

[1115] gccaaccctg acctgcctca caggtttgcc gagagactgc cgctgaacaa ggacgtgatg 1020

[1116] gagacttggt atagccaggg gcccgaaggt tatgtggact accccaccgc tgaccaaaag 1080

[1117] tag 1083

[1118] Sequence Listing (ID): 71

[1119] atgcctaccc tgttcgatcc catccgtctt ggtgcagtta ccgctaaaaa tagaatttta 60

[1120] atggctcctc tcacgcgcgg ccgtgctacg cgtgatcatg tgccaaccga tattatgatt 120

[1121] aaatattatg cccagcgtgc gagtgccggt ctgattattt cagaggcaac aggcattagc 180

[1122] caagaagggt taggttggcc ttatgcgccg ggcatatgga atgaagcgca aacccaagca 240

[1123] tggattccta tcactcaggc cgtgcatgat gcgggcggtc ttatctttgt tcaattatgg 300

[1124] catatggggc gcttggtgcc ttctagtgtc agcggtatgc aacctgtttc agcctcggca 360

[1125] accaaggcac cggatttggc gcatacctat gaaggtaaaa aaccttttga tgttgctcgg 420

[1126] ccactagaaa ttgctgaaat tccacgcttg cttgatgatt atgagcgcgc aacacgtaat 480

[1127] gcactatccg ctggatttga tggggttcaa attcacgcgg ctaatggcta tttaattgat 540

[1128] gaattcttac gagatggtac taatcttcgt aaggatgctt atgggggtac tccagaacat 600

[1129] cgtatccgtt tattacgtga agtgaccgag cgtgttatta gtgttatcgg tgcggaccgt 660

[1130] acctcggttc ggctttctcc taatggtgaa attcaaggtg cctcggatag ccatcctgaa 720

[1131] aatatttttt taccagccgc acggatgctt tctgatctgg ggattgcttt tcttggattg 780

[1132] cgggaaggaa cgcctgaagg tacctttgga aggacagacc agcctaagct ttccccaaaa 840

[1133] attcgtgaag tcttcaatcc accgcttatt cttaatcaag attacaatct tgaaactgcg 900

[1134] caggaggctc ttgattccgg tgtagccgat gcgatcagtt ttggacgtct ctttatctct 960

[1135] aatccagatc ttccaaggcg cttttttgaa ggctcaccgc ttattaaaga caatattgct 1020

[1136] acatggtata cccaaggtgc cgaaggctat accgactatc cccttatcgg taatgaaata 1080

[1137] cccgcataa 1089

[1138] Sequence Listing (ID): 72

[1139] atgcctagct tgtttgatcc catccgcttc ggcgctttta ccgcaaaaaa tagaatttgg 60

[1140] atggcgcctc tgacccgtgg ccgtgccacg cgcgatcatg tccccactga aataatggcc 120

[1141] GAATATTATG CCCAGAGGGC AAGCGCCGGA CTGATTATTT CAGAGCGACT GGCATTAGTT 180

[1142] CAGGAAGGTT TGGGCTGGCC TTATGCTCCG GGAATCTGGA GTGATGCCCA AGTAGAAGCC 240

[1143] TGGCTGCCGA TTACGCAGGC CGTGATGATG CCAGCCGGTC TTATCTTTGC CCAGCTATGG 300

[1144] CATATGGGAC GTATGGTGCC GTCTAATGTC AGTGGGATGC AGCCTGTTGC GCCTTCTGCC 360

[1145] AGTCAGGCAC CCAGATTGGG GCATACCTAT GATGGTAAAA AGCCTTATGA TGTTCCTC 420

[1146] GCTTTGCGAT TGGATGAAAT TCCGCGTCTT CTTGATGATT ATGAAAAGGC TGCCCCTCAT 480

[1147] GCCTTGAAGG CCGTTTTGAT GGCCTACAGA TCCATGCCGT AATGGTTATT TGATTGAC 540

[1148] GAATTTATAC GGGATAGCAC CAACCATCGT CATGATGAAT ATGGGGGTGC AGTTGAAAAC 600

[1149] CGTATTCTGT TTGCTGAAAG ACGTCACCGA ACAGTTATCG AACCCTTGGA AAGAGCGGG 660

[1150] ACGGCCGTTC GTTTATCACC GAATGTTGAA ATACAGGGGA CGGTTGATAG TCTCCCGAA 720

[1151] GTTTTCCTTA TGGTTTCTTA TGGTTTCTTA TGGTTTCTTA TGGTTTCTTA TGGTTTCTTA 780caggttttta taccggcggc caaaatgttg tctgatttgg atattgcctt tttagggatg 780

[1152] cgagaagggg ctgttgatgg cacctttggc aaaacagatc agcccaaatt atcgcctgaa 840

[1153] atccgaaaag ttttcaaacc gcctttggtt cttaatcagg attatacttt tgaaaccgcg 900

[1154] caagctgctc ttgattccgg tgtggccgat gccatcagtt ttggaaggcc ttttatcggt 960

[1155] aatcctgatt tgccacggcg tttctttgag aaagcccccc ttaccaaaga tgtgattgag 1020

[1156] acttggtata cccaaacccc caagggatat acggattatc ctttgcttgg ggattaa 1077

[1157] SEQUENCE ID (ID): 73

[1158] atgaccagcc tgtttgagcc gattgaactg ggaagcattt acgccaaaaa cagaattctc 60

[1159] atggcgccgc tgacacgcgg tcggagcacc cgtgatcatg tgcccacccc catcatggcc 120

[1160] gaatattacg cgcaacgggc cggagccggt ctgatcatct cagaagcgac cgggatcagc 180

[1161] cgcgaaggtc ttggctggcc gtatgcgccg ggcctgtggt cgcaggaaca ggtggaagcc 240

[1162] TGGAAGCCCATCACCGCCGCAGTTTACGCCAAGGGCGGAAAGATTGTGGCCCAGCTCTGG 300

[1163] CATATGGGTCGGATGGTTCATTCAGCGTGACGGGCCAGCAACCTGTGTCCTGCTCGGC 360

[1164] ACAAAAGCGCCTGAAGCCCTCCATACGTACGATGGCAAGCAGGCTCCCAGAGTCGCCC 420

[1165] GCCTCTCACCAAGGAGGACATTGCCCGCATCCTGAACGACTACGAAAATGCTGCTCG 480

[1166] CAACGCCCTTCAGGCAGGCTTTGACGGTGTGCAGATTATGCCGCCAACGGTTATCTGA 540

[1167] TCGGCGGACGGCACCAATCATCGTTCCGACGAATATGGCGGTTCGCCGGAAAAC 600

[1168] CGCATCCGCTTCCTGCGTGAAGTCACCGAACGCGTGATCGCAACGATTGGCGCGCAAA 660

[1169] ACGTCAAGAAGGCTGTCCCCCAATGGCGATACGCAGGGCTGATCGACAGTATCCAGAG 720

[1170] CAGGTCTTTTGTCGGCCTCAAAGCTGCTGAATGACCTCGATATCGCTTTCCTTGAAC 780

[1171] CGCGAGCCCGGACCGAACGGCACGTTTGGCAAGACC GACCA GCCCAAGCTG CATGGTCCG 840

[1172] atccgcgaag tcttcaggaa gccgctggtt ctgaatcagg actacacacg ggaagaagcg 900

[1173] atcgagacag tcgctaccgg tgttgcggac gccatttcgt ttggtcggcc tttcctcgcc 960

[1174] aatccggacc tcgtgcgtcg tctggaagac aatctgcccc agaacaagga cgatatccgc 1020

[1175] acctggtact cgcagggtgc agaaggctat acggattatc cgcttgctcg ctga 1074

[1176] SEQ ID (ID): 74

[1177] atgacgaccc tgttcgaccc gatcaagctt ggcgcaatcg ccgctcccaa ccggatcatc 60

[1178] atggcaccgc tgacgcgcgg tcgttcgagt cgtggccatg ttcccagcgc cctgatggcg 120

[1179] gaatattacg cgcagcgggc cagtgccggt ctcatcatca ccgaagcgac cggcatttcg 180

[1180] caggaaggcc ttggctggcc ctatgcaccg ggcatctggt cggatgagca ggtggaggcc 240

[1181] tggaagccca tcgtgcgcgc ggttcatgac aagggcggcc ggatcgtcat gcagctctgg 300

[1182] cacatgggcc ggatggtgca ttcgaatgtg accggcctgc agcctgtctc ggcgtcgccg 360

[1183] acgaccgcgc cgggcgaagc gcacacctat gatggcaaga agccctacga gcaggcgcgt 420

[1184] gcgctcgaca tttcggaaat cccgcggctt ctggcggatt acgagaacgc gacccgcaac 480

[1185] gcgctggcgg cgggcttcga cggtgtccag atccatgcag ccaacggcta cctgatcgac 540

[1186] gaattcctgc gcgacagcac caacaagcgg accgatgcct acggcggcga accggaaaac 600

[1187] cgcatccgtc tgctgcgcga agtgacggag cgggtgatct cggtcgccgg tgccgatcgc 660

[1188] acggctgttc gtctcagccc gaacggcgag acgcagggca cgatcgacag caatccgatc 720

[1189] tcggtcttcg tgccggcagc gaagatgctg tacgatctcg gcctcgcctg gctcgaactt 780

[1190] cgcgagcccg gcccgaacgg cacgttcggc cggaccgacc agccaaagct gtcgccgcag 840

[1191] atccggcagg tcttcaaggc gccgctggtc ctgaactcgg actacacgct cgaggaagcc 900

[1192] gagacggcgg tgctggaaga tcgggccgat gcgatcagct tcggacgcaa gtttctggcc 960

[1193] aatccggacc tgccgcaccg cttcaagtcc ggtctgccgc ttaacaggga cgagatgaag 1020

[1194] acgtggtatt cccaggggcc gcagggctac gtcgattatc ctgccgcctc ctaa 1074

[1195] SEQ ID (ID): 75

[1196] atgccaaccc tgttcgatcc cattgatttc ggtcccattc acgcgaaaaa ccggatcgtg 60

[1197] atgtccccgc tgacgcgcgg acgtgctgac aaggaggccg ttccgacccc catcatggcg 120

[1198] gaatactacg cccagcgcgc cagtgccggg ctgatcatca cggaagccac gggtatctcc 180

[1199] cgcgaaggtc tgggctggcc gttcgcaccg ggaatctggt ccgatgcgca ggtcgaagcc 240

[1200] tggaagccga tcgtggccgg tgtgcatgca aagggcggaa agatcgtctg ccagctctgg 300

[1201] cacatgggcc gcatggtcca ctcgtccgtg accggaacgc agcccgtctc gtcctccgcc 360

[1202] accacggccc ccggcgaggt ccatacctat gaaggcaaga agccgttcga gcaggcccgc 420

[1203] gcaatcgatg ccgcggatat cagccgtatt ctgaacgact atgagaacgc cgcccgcaat 480

[1204] gcgatccgcg ccggcttcga cggggtgcag atccacgccg ccaatggcta cctcatcgac 540

[1205] gagttcctgc gaaacggtac gaatcaccgc acagatgaat acggcggcgt ccccgaaaac 600

[1206] cgcatccgtt tcctgaagga agtcaccgag cgcgtgatcg ctgccatcgg tgccgaccgc 660

[1207] acaggcgtgc gcctgtcccc caacggcgat acgcagggct gcatcgacag cgcacctgag 720

[1208] acggtctttg tcccggcggc aaagctgctt caggatctgg gcgtggcctg gctcgaactg 780

[1209] cgcgaacccg gcccgaacgg caccttcggc aagacggacc agcccaaact gtccccgcag 840

[1210] atccgcaagg tgttcctgcg cccgctggtg ctcaatcagg actatacgtt cgaggcagca 900

[1211] cagaccgcgc tggcagaagg gaaggctgat gcgatcgcct tcggtcgcaa gttcatctcg 960

[1212] aaccccgacc tgccggagcg cttcgcccgc ggcatcgccc tgcagccgga tgatatgaaa 1020

[1213] acctggtaca gtcagggccc cgaaggatac acggactacc cgtccgccac ctccggcccc 1080

[1214] aactaa 1086

[1215] Sequence Listing (ID): 76

[1216] atgcctagcc tgttcgattc catcgacctt ggcgcagttc acgctgccaa tcgcatcatc 60

[1217] atgtcgcccc tgacgcgtgc gcgtgccacc gagggagctg ttcctacgcc tctcatggtt 120

[1218] gaatattacg cccagcgcgc tggcgccggt cttattattt cggaagccac aggaatttca 180

[1219] cgagaaggtc ttggctggcc ctgggctcca ggaatctgga gtgcagagca ggtggccgcc 240

[1220] tggaagccga tcaccaaggc cgttcatgag cgtggtggga aaattgtatg ccagctttgg 300

[1221] catatgggcc gtatggttca ttcgtctgtg acagggcttc agccggtctc ggcgtctccg 360

[1222] acgactgctc ccgggcaatc ccatacttat gagggcaaga agccctatga agaagcccgc 420

[1223] gagcttcgag ttgatgaaat tcctcgtatt ctggctgatt atgagaatgc ggcacggaat 480

[1224] gcgattgaag ccgggtttga cggtgttcag atacacgctg cgaatggcta tctgatcgac 540

[1225] gaattcctgc gtgatggaac caaccatcgc aaggacgagt acggtggggc cccagagaat 600

[1226] cggatccgtt tgcttcgtga agtgacagag cgcgttgtgg ccacgatcgg tgcggatcgt 660

[1227] acaagcgtgc gtctatcgcc aaatggtgac acgcagggca ccgatgacag cgcgccggaa 720

[1228] aaggttttcg tgcccgctgc gaaggttttg caggatctgg gcgtggcatg gcttgaactg 780

[1229] cgtgagccgg ggcctgaagg aacgtttggc aagactgacg aaccgaagct gtcccctgaa 840

[1230] attcgtaagg tgtttagtcg tcctctggtc ctcaatcagg attatacgct tgaggatgct 900

[1231] cagaaggctg tctcttccgg tctggccgat gctgtgagtt ttgggcgcaa atttattgca 960

[1232] aacccggatc tccctcgccg ctttgctgaa gaaatccctt tggcgaagga cgacatggcg 1020

[1233] acatggtaca gtcagggccc aaagggttac acggactacc ccttcgcgga tgaataa 1077

[1234] Sequence Listing (ID): 77

[1235] atgccgaacc tcttcgaccc gctccaactc ggccccatca cgctccccaa ccgcgtcatc 60

[1236] atggccccac tcacgcgcct gcggggcacg cccgaccaca tccccacgcc cctcatcgcg 120

[1237] GAGTACTACG CCCAGCGCGC CTCCGCCGGC CTCATCATCT CCgaaggcac gcccgtcagc 180

[1238] CCCATGGGCG TCGGCTACGC GCAGGTCCCg GGcatctggt cggagcaaca gactgagcag 240

[1239] TGgtcgcaca tcaccaccgc cgtccacgcc gccggcggcc gcatcttcgc gcagatctgg 300

[1240] CACgtcggcc gcgtctcgca cccactcttc ctcaacggcc agcagcccgt tgcgcccacc 360

[1241] GCTCTCGCg CCgGAGGGCT TcGTCTCGCT CGTTCGCCCT CAGAGGCCCT TTGAGACGCC C 420

[1242] CGCGCGCTCG ACATCGCCGA AATCCGCAGC ACCATCGCCG ACTACAAGCG CGGCgCTCAG 480

[1243] AACGccaagg CCgCCGGCTT CGACGGCGTC GAACtCCACG GCGCCaATGG CTACCTCATC 540

[1244] GACCAGTTCC TGCAGTCAGG CACCAACCAC CGCACCgACG CCTACGgtGG CCCGgtCGAA 600

[1245] AACCGCGCCC GCTTcatGCT GGAGGCAGTC GATGCCGTCT CCGAGGTCTG GGGCGCCGAC 660

[1246] CGTGTcGGCA TGCACCTGGC CCCGCgCGGA GGATATATGA GCATCTCCGA CGCCaACCC 720

[1247] tccgagacct tcggctacgt cgctactgag ctcggcaagc gcggcctcgc cttcctcatg 780

[1248] tcccgcgagc acgaagggcc tgattggctc acgccacagc tcaagcagca gttcggcggc 840

[1249] gtctacatcg ccaacgaggg cttcacctat gagagcgcaa acgccgccgt cgaacgcggc 900

[1250] gactgcgacg ccgtcggctt cggcaagctg ttcatctcca accctgatct gcccgcacgc 960

[1251] tttgcccgcc aggcagaact cacggctccc atcccggaaa ccttctactc ccacagcccc 1020

[1252] gagggctaca tcgactaccc cgcactcgcc taa 1053

[1253] Sequence Listing (ID): 78

[1254] atgcccacac tctttgaccc gatccgtatc ggcgacctcg accttcccaa ccgcgtcatc 60

[1255] atggcgcctc tgacgcgttc gcgcgcagtg ggcggcggcc gcgtgcccaa cgcgttgatg 120

[1256] gccgaatact atgtacagcg cgcttcagcg ggcctgatcc tgagcgaagc cacggccgtg 180

[1257] actccgcaag gcgtgggtta tgccgacacc ccgggcatct ggtcggaaga acaagtggct 240

[1258] ggctggaagc acgttaccga cgccgtgcac gccgccggcg gccgcatctt cctgcaactg 300

[1259] tggcacgtgg gccgcatctc cgacccggtc ttcctcgacg gcgaactgcc ggtggcaccc 360

[1260] agcgcgatcg cggccggcgg ccatgtcagc ctggtgcgcc ccaagcgcgc ctttgtcacc 420

[1261] ccgcgcgcgc ttgaaaccga ggaaatcccg ggcattgtcg ccgcctaccg gcacggcgcg 480

[1262] gagaacgcca aggccgccgg cttcgacggc gttgaagtgc acggcgccaa tggctacctg 540

[1263] ctcgatcaat tcctgcaaga cagcaccaac cagcgcaacg atgcctacgg cggctcgatc 600

[1264] gaaaatcgcg cccggctgct gctggaagtc acggatgcct gcatcgcggt ttggggtccg 660

[1265] gcgcgcgtgg gcgtgcacct ggccccgcgc ggcgatgccc acagcatggg cgactccgac 720

[1266] cccgccgcca ccttcggcta tgtggcacgc gaactgggca agcgcggcat tgccttcatc 780

[1267] tgctcgcgcg aagcgctcgg cgataaccgc ctggggccgg aactgaagcg ggccttcggc 840

[1268] ggcacctata tcgccaacga aaaaatgacc aaggccaccg ccgagcacgt cttgcaggcc 900

[1269] ggcgaagccg acgcagtggc cttcggccag ctcttcatcg ccaacccgga cctgccgcgc 960

[1270] cgcctgcaac tggatgcgcc gctcaacgcg ccgcagccgg aaaccttcta ccatcccggc 1020

[1271] gccgaaggtt atatcgatta ccccgcgctc gcctga 1056

[1272] SEQ ID (ID): 79

[1273] atgccaactt tatttgatac cctcaccctg ggtgatttaa ctctgaaaaa ccgtattgtg 60

[1274] atggcgcctt taacccgctg tcgcgccgac gaaggccgtg tgcccaatgc catgatggct 120

[1275] gagtattatg cccagcgcag cagcgcaggt ttaattttat ccgaagccac atcagtcaca 180

[1276] gctatgggtg tgggttaccc tgacacaccg ggtatttggt ctgacgccca agtgcaaggc 240

[1277] tggaagctga tcactgacgc agtgcacgaa gcgggcagcc gtattttcct gcagctgtgg 300

[1278] catgtaggtc gtatttccga tccatcttac ttaaatggcg cacaacctgt agcaccaagc 360

[1279] GCGTCGGCCGGTCATATCAGCCTGGTACGTCCGCTGAAAGATATGACGAACCA 420

[1280] CAGTTCCTGGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTT 60

[1281] AACCACGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTTTC 120

[1282] GACCAGTTTTTACAGGACAGCACTAATTTACGTGACGACGAATACGGTGGTTCC 180

[1283] AACCACGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTTTCTGGTTTC 240

[1284] AGAGTCGCATGCATTAGCGCCCCCGATGGATGCTCACGATATGGGTGATTCC 300

[1285] ACAGCCACTTTTGTTATGTTCGCCACAGAGCTGGGTA AAAAGAGGTATAGCTTT 360

[1286] ACCCGTGAACATGCAGCTGACGACAGCATCACGCCGCTGATCAAACAGCTGTT 420

[1287] CCAGTGATTGCGAATGAAAAATTCAACA AAGCAGAAGCGAATCAGTGGCTGGCC 480

[1288] AAAGCCGACGCAGTAGCCTTTGGTTATTCTTTTATTGC AACCCC 540

[1289] ttagagctgg atgccccact caacgagcca cgcaaagaac tgttttacgg taaaggcccg 1020

[1290] ttaggttata ccgattatcc aaccttagcc tag 1053

[1291] Sequence number (ID): 80

[1292] atggcgacta ttttcgaccc catcaaactc ggcgacatcg agttgaagaa ccgcatcatc 60

[1293] atggccccgc tcacccgctg ccgcgccgac gcaggtcgcg tgcccaacgc tctgatggcc 120

[1294] gaatattacg tgcaacgcgc ctccgccggc ctgatcctca gcgaagcaac ttcggtcacg 180

[1295] ccgatgggcg tgggctaccc ggacaccccg ggcatctggt ccaacgacca ggtgcgcggc 240

[1296] tggtccaacg tcaccaaggc gatccacggc gctggcggca agatcttcct gcaactgtgg 300

[1297] cacgtgggcc ggatctccca cccgtcgtac ctgaacggcg aaaccccggt ggcgcccagc 360

[1298] gcgatccaac ccaagggcca cgtgagcctg gtgcgtccgc tggccgacta cccgacccca 420

[1299] cgcgcactgg aaaccgctga aatcgccgac atcgtcgagg cgtaccgcgt cggtgccgag 480

[1300] aatgccaagg ctgccggttt cgatggcgtg gaaatccacg gcgccaacgg ctacctgctc 540

[1301] gaccagttcc tgcaaagcag caccaaccag cgcaccgaca gctacggcgg ctccctggaa 600

[1302] aatcgtgccc gcctgctgtt ggaagtgacc gacgcggcca ttgaagtctg gggcgccggc 660

[1303] cgggttggcg tgcacctggc accgcgcgcc gactcccatg acatgggtga cgagaaccgc 720

[1304] ctggaaacct tcagctacgt ggctcgcgag ctgggcaaac gtggcatcgc cttcatctgc 780

[1305] tcccgtgaaa aggaaggcga tgacagcatc ggcccgcaac tcaagcaggc tttcggcggc 840

[1306] ccgtacatcg ccaatgaacg cttcaccaag gacagcgcca atgcctggct ggccgagggc 900

[1307] aaggccgatg ccgtggcctt cggagtgccg ttcattgcca acccggacct gccagcacgc 960

[1308] ttgaaagccg atgcaccact gaacgaagca catccggaaa ccttctatgg caaagggccg 1020

[1309] gtggggtaca tcgattaccc tgtgctctga 1050

[1310] Sequence Listing (ID): 81

[1311] atggcaacta ttttcgatcc gatcaaactg ggcgacctcg agctgtccaa ccgcatcatc 60

[1312] atggccccgc tgactcgctg ccgcgccgac gaaggccgcg tacccaacgc actgatggcc 120

[1313] gagtactacg tgcaacgtgc ctccgccggc ctgattctca gcgaagccac ttcggtgacg 180

[1314] ccgatgggcg tcggctatcc ggacaccccg ggcatctggt ccaacgatca ggtacgcggc 240

[1315] tggaccaaca tcaccaaagc cgtacacgct gccggcggca agatcgtcct gcaactttgg 300

[1316] cacgtcggcc gcatctcgca cccgttgtac ctgaacggcg aagcaccggt cgcgccgagc 360

[1317] gccatccagc ctaaaggcca cgtcagcctg gtgcgtccac tggccgatta cccgactcca 420

[1318] cgcgccctgg aaaccgctga aatcgccgag atcgtcgagg cctaccgcac cggtgccgag 480

[1319] aacgccaagg ccgccggttt cgacggcgtg gaaatccacg gcgccaacgg ctacctgctc 540

[1320] gaccagttct tgcaaagcag caccaaccag cgcaccgaca attacggcgg ctccctggaa 600

[1321] aaccgtgcgc gtctgttgct ggaagtgact gatgccgcga tcgacgtctg gggcgccggc 660

[1322] cgtgtcggtg tgcacctggc accgcgcgcc gactcccacg acatgggcga cgacaacctc 720

[1323] gccgagacct tcacctatgt tgctcgcgag ctgggcaagc gtggcatcgc cttcatctgc 780

[1324] tcccgcgaga aagaaggcgc cgacagcctc ggcccacaac tgaaagaagc ctttggcggc 840

[1325] gcgtacatcg ccaacgagcg tttcaccaag gacagcgcca atgcgtggct ggctgaaggc 900

[1326] aaggctgacg ctgtagcgtt cggcgtgcca ttcattgcca acccggacct gccggcacgc 960

[1327] ctgaaagccg atgccccgct gaacgagccg cgtcctgagc tgttctatgg caaaggcccg 1020

[1328] gtcggctaca tcgactaccc gacgctgtaa 1050

[1329] Serial number (ID): 82

[1330] atgtcgtaca tgaactttga ccctaagcca ttgggagaca ccaatatctt caagccaatc 60

[1331] aagatcggta acaatgagct aaaacacaga gtagtcatgc cagcattgac tagaatgaga 120

[1332] gccattgcac caggaaacat cccaaacact gaatgggccg aggaatacta cagacaacgt 180

[1333] tctcaatacc ctggtaccct tattatcacg gaaggtactt tcccttctgc gcaatcaggt 240

[1334] ggttacccaa atgtgccagg tatctggtcc aaagagcaat tggctgaatg gaaaaagatc 300

[1335] ttcaatgcaa tccatgagaa caaatcgttc gtgtgggtgc aattgtgggt tctaggtaga 360

[1336] caagcatggc cagaagtgtt gaagaaggaa ggtttgcgtt acgatagtgc taccgatgac 420

[1337] ttgtacatgg gtgaagaaga aaaagagcgt gccttaaagg ctaacaaccc acagcacggt 480

[1338] atcaccaagg aagaaatcaa gcagtacatc aaggagtacg tggatgctgc caagaaagcc 540

[1339] atcgatgcag gtgcagacgg tgtgcaaatc cattctgcca acggttactt gttgaaccag 600

[1340] tttttggacc ctatttctaa caacagaacc gacgagtacg gtggatcgat cgagaaccgt 660

[1341] gcgagattca ctttggaagt ggtcgatgcc gttgtcgatg cagttggtgc cgaaagaacc 720

[1342] tccatcagat tctctccata cggtactttt ggtaccatgt ccggtggtga gaaccctggc 780

[1343] atcgttgctc aatatgcata cgtcattggt gagttggaaa agagagctag agctggcaag 840

[1344] agattggcgt tcatcgattt ggtcgagcct cgtgtgaccg acccattcct accagaattc 900

[1345] gagaagtggt tcaaggaagg taccaacgaa ttcatctact ctatctggaa gggtccagtt 960

[1346] ctcagagttg gtaactatgc tttggaccca gatcaagcca ctctcgactc taagaagcct 1020

[1347] aacactttga tcggttacgg tagatccttc atcgccaacc cagacttggt gtaccgtttg 1080

[1348] gaaaagggtt tgccattgaa caagtatgat agaaacacct tttacacatt cactaaggaa 1140

[1349] ggttacaccg attacccaag ctacgaagaa tccgtcgcaa agggttacaa gaaagaggaa 1200

[1350] aagaagtact aa 1212

[1351] SEQUENCE ID (ID): 83

[1352] atgtcttttg ttcaagattt caaaccaatt gcactagctg acactaagct tttcaagcca 60

[1353] atcaaaattg gtaacaatga attggcacac cgtgtggtta tgccaccttt gaccagaatg 120

[1354] agagctactc atccaggcaa tgttcctaac aaggactggg ctgttgagta ctatgaccaa 180

[1355] cgttctaaaa gacctggaac tttgataatc actgagggtg ctttcccatc agcacaaagt 240

[1356] ggtggttacg acaatgtacc aggtatctgg tctccagcac aacttgaaca atggaaaaag 300

[1357] atcttcgcca agattcacga gaacaagtct tttgtctggg ttcaactttg ggttttagga 360

[1358] agacaatctt ttgctgatac gttggcaaga gatggccttc gttatgattc tgcttccgat 420

[1359] ggagtttaca tggacgaaga gcaacgtgaa agagctgtga agagcaataa cccacaacat 480

[1360] ggtttgacca aggctgaaat taaacagtac attagcgaat acgtcgatgc cgccaagaag 540

[1361] tccattgaag caggtgccga tggtgtggaa attcacagtg ccaacggtta cctattaaac 600

[1362] caattcttgg accctatttc caacaagaga accgatgaat atggtggatc tatcgagaac 660

[1363] agagctcgtt tcgtgctgga agttgtcgat gctgtcaccg aggctatcgg ttgcgacaaa 720

[1364] gttggtatca gattatctcc atatggtact ttcggtacta tgtctggtgg ttctgagcca 780

[1365] ttgatcgttg ctcaatttgc ctatgtattg ggtgaattgg aaaagagagg aaaggctggg 840

[1366] aaacgtctat cattcgttca ccttgtcgaa cctcgtgtga caaatccatt ctacactgaa 900

[1367] ggccaaggtg agtacaccga aggcaccaat gactttgcat actctgtctg gaaaggtcca 960

[1368] atcatcagag ctggtaactt ggctctacac ccagaagttg ttaagaaaat ggtcgaagac 1020

[1369] gacagaactc tgataggtta cggtagattt tttatctcaa atcccgatat cgtcgaccgt 1080

[1370] gtggaaaaag gtttgccatt gaacaagtac aacagagata ctttttacgc catgacagct 1140

[1371] aatggttacc ttgactaccc aacttatgat gaggcagtta agcttggtta caaatag 1197

[1372] SEQUENCE ID (ID): 84

[1373] atgccatttg taaaaggttt tgagccgatc tccctaagag acacaaacct ttttgaacca 60

[1374] attaagattg gtaacactca gcttgcacat cgtgcggtta tgcccccatt gaccagaatg 120

[1375] agggccactc accccggaaa tattccaaat aaggagtggg ctgctgtgta ttatggtcag 180

[1376] cgtgctcaaa gacctggtac catgatcatc acggaaggta cgtttatttc ccctcaagcc 240

[1377] ggcggctatg acaacgcccc tgggatttgg tctgatgagc aggtcgctga gtggaagaat 300

[1378] atctttttag ccatccatga ttgtcagtcg ttcgcgtggg tacaactttg gtctttaggc 360

[1379] tgggcatcct tcccagacgt attggcaaga gacgggttac gctatgactg tgcatctgac 420

[1380] agagtgtata tgaatgctac gttacaagaa aaggccaaag atgcgaataa tctcgaacat 480

[1381] agtttgacta aagacgacat taaacagtat atcaaggatt acatccatgc ggctaagaat 540

[1382] tctatcgcgg ctggcgccga tggtgtagaa attcatagcg ccaatgggta cttgttgaat 600

[1383] cagttcttgg atccacattc taataagagg accgacgaat acggcggaac gatcgaaaac 660

[1384] agggcccgct ttacactgga ggttgtcgat gctcttatcg aaactatcgg tcctgaacgg 720

[1385] gtgggtttga ggttgtcgcc gtacggcact tttaacagta tgtctggggg tgctgaacca 780

[1386] ggtattatcg ctcaatattc gtatgttttg ggtgaattag agaagagggc aaaggctggt 840

[1387] aagcgtttgg cctttgtgca cctcgttgaa ccacgtgtca cggacccatc gttggtggag 900

[1388] ggcgaaggag aatattccga gggtactaac gattttgcct actctatatg gaagggtcca 960

[1389] atcatcagag ctggtaatta cgctcttcat ccagaagtgg ttagagaaca agtaaaggat 1020

[1390] cccagaacct tgataggcta tggtagattc ttcatctcta acccagattt agtctaccgt 1080

[1391] ttagaagagg gcctgccatt gaacaagtat gacagaagta ccttctacac catgtccgcg 1140

[1392] gaaggttata ccgactaccc aacatatgaa gaggcagtag atttaggttg gaacaagaac 1200

[1393] tga 1203

[1394] SEQUENCE ID (ID): 85

[1395] atgccatttg ttaaggactt taagccacaa gctttgggtg acaccaactt attcaaacca 60

[1396] atcaaaattg gtaacaatga acttctacac cgtgctgtca ttcctccatt gactagaatg 120

[1397] agagcccaac atccaggtaa tattccaaac agagactggg ccgttgaata ctacgctcaa 180

[1398] cgtgctcaaa gaccaggaac cttgattatc actgaaggta cctttccctc tccacaatct 240

[1399] gggggttacg acaatgctcc aggtatctgg tccgaagaac aaattaaaga atggaccaag 300

[1400] attttcaagg ctattcatga gaataaatcg ttcgcatggg tccaattatg ggttctaggt 360

[1401] tgggctgctt tcccagacac ccttgctagg gatggtttgc gttacgactc cgcttctgac 420

[1402] aacgtgtata tgaatgcaga acaagaagaa aaggctaaga aggctaacaa cccacaacac 480

[1403] agtataacaa aggatgaaat taagcaatac gtcaaagaat acgtccaagc tgccaaaaac 540

[1404] tccattgctg ctggtgccga tggtgttgaa atccacagcg ctaacggtta cttgttgaac 600

[1405] cagttcttgg acccacactc caataacaga accgatgagt atggtggatc catcgaaaac 660

[1406] agagcccgtt tcaccttgga agtggttgat gcagttgtcg atgctattgg ccctgaaaaa 720

[1407] gtcggtttga gattgtctcc atatggtgtc ttcaacagta tgtctggtgg tgctgaaacc 780

[1408] ggtattgttg ctcaatatgc ttatgtctla ggtgaactag aaagaagagc taaagctggc 840

[1409] aagcgtttgg ctttcgtcca tctagttgaa cctcgtgtca ccaacccatt tttaactgaa 900

[1410] ggtgaaggtg aatacaatgg aggtagcaac aaatttgctt attctatctg gaagggccca 960

[1411] attattagag ctggtaactt tgctctgcac ccagaagttg tcagagaaga ggtgaaggat 1020

[1412] cctagaacat tgatcggtta cggtagattt tttatctcta atccagattt ggttgatcgt 1080

[1413] ttggaaaaag ggttaccatt aaacaaatat gacagagaca ctttctacaa aatgtcagct 1140

[1414] gagggataca ttgactaccc tacgtacgaa gaagctctaa aactcggttg ggacaaaaat 1200

[1415] taa 1203

[1416] SEQUENCE ID (ID): 86

[1417] atgtcatttg taaaagattt taagccacaa gctttaggtg acaccaacct attcaaacca 60

[1418] atcaagatcg ggaacaatga acttttgcac cgtgctgtca ttcctccatt gaccagaatg 120

[1419] agagctcttc accctggtaa tatcccaaac agggactggg cagtcgaata ctacacccaa 180

[1420] cgtgctcaaa gacctggtac catgattatc actgaaggtg ccttcatatc cccacaagcc 240

[1421] ggcggttacg ataacgctcc aggtgtttgg tcggaagaac aaatggtgga atggaccaaa 300

[1422] atcttcaacg ctattcatga aaagaaatcg ttcgtttggg ttcagttatg ggttttgggt 360

[1423] tgggctgctt tcccagacaa tcttgccaga gatggtttgc gttacgattc agcttctgac 420

[1424] aacgttttca tggatgccga gcaagaagct aaggccaaga aggccaacaa cccacaacac 480

[1425] agcctaacca aggacgaaat caagcaatac attaaggaat acgtccaggc tgccaagaac 540

[1426] tctattgctg ctggtgccga tggtgttgaa attcacagtg ctaacggtta cttgttaaac 600

[1427] cagttcttgg accctcattc caatactaga accgatgaat atggtggatc tattgaaaac 660

[1428] agagctcgtt tcaccttgga agttgttgat gctcttgtcg aagccattgg tcatgaaaaa 720

[1429] gttggtttga gattgtcccc atacggtgtt ttcaacagta tgtctggtgg tgccgagacc 780

[1430] ggcattgttg cccaatatgc ttacgttgct ggtgaattag aaaagagagc taaagccgga 840

[1431] aaacgtttag cttttgttca tttggttgaa cctcgtgtaa ctaacccatt cttgactgaa 900

[1432] ggggagggtg aatacgaagg aggtagcaac gattttgttt actccatctg gaagggccca 960

[1433] gtcattagag ctggtaattt tgctctccac ccagaagtcg ttagagaaga agttaaggac 1020

[1434] aagagaacct tgatcggtta cggtagattc ttcatttcta acccggattt ggttgatcgt 1080

[1435] ttggaaaaag gtctacctct gaacaaatat gacagagata ctttctacca gatgtctgct 1140

[1436] catggttata ttgactaccc cacctatgaa gaagctctca aattaggctg ggacaaaaag 1200

[1437] taa 1203

[1438] Sequence Listing (ID): 87

[1439] atgactgtcg gattggaaca atcgaattta tttaaaccga ttactattgg taaaaataca 60

[1440] ctggatcaaa gggtagcttt cgctcctaca acaagattcc gtgctgcaga tgatcatact 120

[1441] ccaagcgact tgatgctaca atactattct gatagagcac aagctcctgg ttcgttgctc 180

[1442] attacggaag ccactttcat ttctcctcgc gctggcttat accctaatat tcctggcatt 240

[1443] tggaatgaga aacatgttca aggatggaaa aagattactg atgcagtaca tgctaaagga 300

[1444] agctatatgg cgtgtcaatt ttggttctta ggaagagttg gatccccaga gcttttgaaa 360

[1445] aagcatggct tggatttgat atctccctct gctttatatg aaagcgaaga gtctaagaag 420

[1446] gctgcagaag ctgcaggcaa tcctgtgaga gcattgactg aaaaggaaat caagggcatt 480

[1447] atttatgaag attacaagaa tgcagcaatc aatgctatgg aagctggatt tgattatgtg 540

[1448] gaaattcata gtgcacatgg atacatgctt gatcaattct tacagcccgc tacgaatcaa 600

[1449] agaacagata actatggtgg ttctattgag aagcgtgcaa gaatcgtgct tgagattatc 660

[1450] gaccttttaa gcgatacaat tggtgctgaa aagcttgcaa tcagattgtc tccttgggcc 720

[1451] aaattccaag gaatgaaagc tgaacaagat actgtgcatc ctattaccac atttagttat 780

[1452] gtggtgaatg agcttcaaaa acgtgcaaac aatggtaaac agcttgctta tctttccctt 840

[1453] gtggaaccta gggtccaagg aaacttggat gtcaacacat ctgacattgt tggttccaac 900

[1454] gactttataa aaaaattatg gaaaggagcc attttgcaga gtggtaatta tacttatgac 960

[1455] agtcctgagt ttaagttatt gaaggctgat gtcaatggtg acaaccgtac tatgattgga 1020

[1456] ttctcgagat attttacatc aaatccagat ttaattgata gattaaagaa gggtcttgag 1080

[1457] cttactcctt acgttcgttc tttgttctat gctactaaca actatggtta taacactttc 1140

[1458] gcaaattatg gcaaggaatt gcaatttgat cccaaaaaag aagaaaagag acgtcctgtt 1200

[1459] tctttgatct ga 1212

[1460] Sequence Listing (ID): 88

[1461] atgtcttcag tcaaaatttc tccattgaag gattctgaag cattccagtc tatcaaagtt 60

[1462] ggtaacaaca ctcttcaaac caagattgtc tatccaccaa ctactagatt tagagcttta 120

[1463] gaagaccaca ctccttctga tttgcaattg cagtactatg gcgacagatc cactttccca 180

[1464] ggtactttgc ttatcactga agctactttt gtctctcctc aagcctctgg ttatgaaggt 240

[1465] gctgctccag gtatttggac tgacaagcac gctaaagcat ggaaggttat tactgataaa 300

[1466] gttcatgcca acggttcttt cgtttcaacc cagttgattt ttttgggaag ggttgcagat 360

[1467] ccagctgtta tgaagacccg tgggttgaat ccagtttctg cctctgctac ttatgaaagt 420

[1468] gatgccgcta aagaagctgc cgaagcagtt ggtaaccctg ttagagcttt gactacccaa 480

[1469] gaagtcaagg atcttgttta cgagacttac accaacgctg ctcagaaggc catggatgct 540

[1470] ggtttcgact atattgaact ccatgctgct cacggctacc ttttagatca atttttgcaa 600

[1471] GAGAATTCGAGATCAAAGAATTCATGATTAACGGTGGATCCATTGAGAACAGAGCCAGGTTA 660

[1472] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1473] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1474] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1475] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1476] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1477] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1478] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1479] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1480] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1481] AATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTCCTTGAAGTTAATTC 660

[1482] Sequence Listing (ID): 89

[1483] atggaggaag ttcgtaataa acaagtggtc ttcaaagatt acattaacgg cttcccgaaa 60

[1484] gaaagcgaca tgctgctcaa atccagctct accatctgtc tcaaactgcc gcagggctct 120

[1485] aacggcgttc tggtaaaaaa cctgtacctg tcctgtgacc catatatgcg tgctcgtatg 180

[1486] accaaaactg aaggcagcta ctttcctccg ttcaccccgg gtagcccgat ctctggttat 240

[1487] ggtgttgcga aagtgctgga ctccggtcat ccagacctga agaaaggtga tctggtttgg 300

[1488] ggtggcaccg gctgggagga atatagcatc attgacgctc cggaatctct gtttaaaatt 360

[1489] cagcataccg atatgccgct gtcttattac actggcattc tgggcatgcc gggtatgacc 420

[1490] gcttatattg gtttttatga aatctgcgca ccgaagaaag gcgagtacgt tttcgtgtcc 480

[1491] gctgcatccg gtgctgttgg ccagctggtt ggtcagtttg ctaaactgtc tggctgctac 540

[1492] gttgtaggtt ctgctggtac taaagaaaaa gtagatctcc tgaagaacaa attcggtttt 600

[1493] GATGAGGCCT TAACTATAAA GAAGAGCAGG ACCTGAACGC TGCGCTGAAG CGTTATTTTC 660

[1494] CCGGACGGCA TC GACATCTAT TTTGAAAATG TAGGCGGTAA ATGCTGGAAA GC GGTGCTG 720

[1495] AGCAACATGC GTCTGAACGG TCGCATCTCC GC GTGCGGTAT GATCAGCCAG TACAACCTG 780

[1496] GAACAGCCGG AAGGTGTTTG CAACCTGTTC CTCCTGGTGG GCA AACGTCTG CGCATGCAG 840

[1497] GGCTTTCATC GTTTCTGATT ATTACCACCT GTACCCAAAA TACATGGAGA TGGTTATGCC G 900

[1498] CTGATCAAAC AAGGTACCAT CAGCTACATT GAAGATATCG TTGAAGGCCT GGAATCCGCG 960

[1499] CCAGCAGCGC TG GTTGGCCTG TTCTCTGGTC GTAACGTTCG GCA AACAGGTC GTTGTAGTC 1020

[1500] GCTCGTGAA TGA 1032

[1501] SEQUENCE ID (ID): 90

[1502] ATGGAGGAAG TAAAGAACAA GCAGGTAGTC CTGAAAGACT ACATCAACGG CTTCCCGAAA 60

[1503] GAA TCCGATATG CTCCTGAAAT C TTCCTCTAC CATCTGCCTG AAAC TGC C AAGGTTC T 120

[1504] aacggcctcc tggtgaaaaa cctgtatctg tcctgcgacc cgtacatgcg caaccgcatg 180

[1505] agcaaatccc agggtagcta cgtcgactct ctgaccccgg gcctgccgat caccggctac 240

[1506] ggtgttgcta aggtcctgga ctccggtcac tccgatttca aaaagggtga cctcgtttgg 300

[1507] ggttggacgg gctgggagga atattccatc attgatgctc cggaatctct gttcaaaatt 360

[1508] cagcacactg acatgccgct gtcctactat accggcatcc tgggtatgcc gggcatgacc 420

[1509] gcgtatgcgg gtttctacga aatctgtgct ccgaagaaag gcgaatatgt ctttgtctct 480

[1510] gcggcttccg gtgcggtcgg tcagctggtt ggtcagtttg ccaaactgtc cggctgttac 540

[1511] gtcgttggta gcgcaggcac caaagagaaa gtggacctcc tgaaaaacaa gttcggtttc 600

[1512] gacgaagcgt tcaattacaa agaggaacag gatctgaacg cggccctgaa acgttatttc 660

[1513] ccggacggta tcgacattta cttcgaaaac gttggcggta agatgctgga agcagttctg 720

[1514] ccggacggta tcgacattta cttcgaaaac gttggcggta agatgctgga agcagttctg 720agcaacatgc gtctgaatgg ccgcatctct gcatgcggca tgatttctca gtataatctg 780

[1515] gaacagccgg aaggcgtgtg caacctcttt ctcctggtgg gtaaacgtct gcgtatgcaa 840

[1516] ggcttcattg tatctgacta ttaccacctg tacccgaagt atatggaaat ggttatgccg 900

[1517] ctgatcaaac agggtaccat cagctatatt gaagacatcg tggagggcct ggaaagcgca 960

[1518] cctgcggctc tcgtaggcct gttctccggt cgtaatgtgg gtaaacaggt ggtcgtagtt 1020

[1519] gctcgcgaat aa 1032

[1520] Sequence Listing (ID): 91

[1521] atggcggaag ttgtggaacg ttccccggag gtagttatcg tccgtaataa acaggtaatt 60

[1522] ttcaaggatt atgtgaatgg ctaccctaag gaaacggaca tggttgtgac ttccgacgct 120

[1523] accatccgtc tgaaactgcc ggaaaacgaa tccggcctca tcctgactaa aaatctgtac 180

[1524] ctgtcctgcg atccttacat gcgtggccgt atgtccaaga ccagcgaggg tagctacgtt 240

[1525] ccatccttta cgccgggctc cctgattagc ggttatggcg ttgcgaaagt gctggacagc 300

[1526] acccacccag agtacaagaa aggcgacctg atttccggca tcattagctg ggaggaatac 360

[1527] tccctgatca aaaacccgga actgttcatc aaaatccaac acaccgacgt gccgctgtct 420

[1528] tattacaccg gtattctggg tatggctggt gtgactgctt atgctggttt ctacgaaatc 480

[1529] tgctccccga agaaaggtga caccgtgttc gtgagctccg cgtccggcgc agttggtcag 540

[1530] ctcgtcggcc agttcgctaa actgcacggt tgttatgtcg tgggttctgc tggttccaaa 600

[1531] gaaaaagttg atctcctgaa aaacaaattt ggtttcgatg aggcttttaa ctataaagag 660

[1532] gaacacgacc tgaacagcac cctgaagcgt tgtttcccag acggcatcga tatctatttc 720

[1533] gaaaacgttg gcggtaaaat gctggatgcg gttctgtgta acatgcgcct gcacggtcgt 780

[1534] attgcagttt gcggtatgat ctctcagtac aacctgaacg aacaccaagg tattaataac 840

[1535] ctgatcttcg tgatcctgaa acgtatccgt atggaaggct tcctcgtgac tgaccattac 900

[1536] cacctgtttc cgaaatttct ggagatggtg ctgcctctga tccaggaagg taaaattacg 960

[1537] tacgttgaag atactatcga aggtctggaa aatgccccgg cggctctggt tggtctgttc 1020

[1538] tctggcaaaa acgttggtaa acaaatcgtc gacctgaccc aggaataa 1068

[1539] SEQ ID (ID): 92

[1540] atgggtgaga tggtcgagaa caagcaaatt gtgttgaaag attatgtgag tggctatcca 60

[1541] aaggagtctg acatggtgac gcaagtcagt aagatgagtt taaatgtccc ccatggttca 120

[1542] aacggcattg ttgtcaagaa tctgtacttg agttgcgacc cttacatgcg tccccgcatg 180

[1543] acaaagagcg aaggcggata cgttgactcg ttcactccgg gtcagccgat cacgggctac 240

[1544] ggtgtggcaa aggttttgga ctcagggacc cctaaattta agaaaggtga tctcgtttgg 300

[1545] ggattcaccg gctgggaaga gtattccttg attacaaaga cggacacact tttcaaaatt 360

[1546] GAACACACCG AC GTGCCATT GTCGTACTAC ACAGGGCTCT TGGGAATGC CTGGCATGACC 420

[1547] GCATACGCAG GCTTCTACAA GGTTCGCCAC CCC AAGAAGGG CGAATATGTT TTCGTATCC 480

[1548] GCTGCAAGCG GGGCTGTGGG ACAGCTTGTC GGCCAATTTG CAAAGCTTCT TGGCTGCTAC 540

[1549] GTTAGTCGGA AGTGCAGGCT CGAAAGAAAA GTGGATTTGC TGAAGAACAA GTTTGGTTTC 600

[1550] GACGAGGCAT TTAATTACAA GGAAGAGGAA GACTTGGCAG CGGCTCTTA A GC GTTATTTT 660

[1551] CCGGACGGGA TCGACATCTA TTTCGAGAAT GTAGGCGGCA AGATGCTGGA CGCAGTCCTT 720

[1552] GTTAACATGC GCCCTCACGG CC GTATTGCC GTTTGTGGTA TGATCTCGCA ATACAACCTT 780

[1553] GAAAAGCCGG AAGGATCTAC AATTAACTT TATGTGATCA TGAAGCAATT GC GTATCGAG 840

[1554] GGCTTTCTGG TGTTTCGATT ACTATCACTT GTATCCTAAG CTCCTTGAGC TTGT CCTGCCG 900

[1555] TATATCAAAG AGGGGAAGAT TAAC TATGTAGAG GATATTGCAG AGGGGCTCGA ATCAGCC 960

[1556] cccgccgcgt tagttggctt attttcaggc cgcaatgttg ggaagcaggt agttgccgtg 1020

[1557] gcacgtgagt aa 1032

[1558] Sequence number (ID): 93

[1559] atggcgagcg gcggcgaaat gcaagtgtcg aacaagcaag ttattttccg tgactacgtt 60

[1560] accggattcc caaaggagtc ggatatggaa ctgactacac gctctatcac tctgaagctt 120

[1561] cctcaaggta gtaccgggtt actgttgaag aacctctatt tatcttgtga tccctatatg 180

[1562] cgtgcccgta tgacgaatca ccaccgtctc agctatgtag actctttcaa gccaggtagc 240

[1563] cctattattg gatatggcgt cgcgcgtgta ttggagagtg gcaaccctaa attcaatcca 300

[1564] ggggacctcg tttggggctt cactggctgg gaagaataca gcgtgattac cgcgacagag 360

[1565] agcttattta agatccacaa tacggacgta ccgttgtctt actataccgg cttattaggc 420

[1566] atgcccggaa tgacggcgta tgccgggttt tatgagatct gcagcccgaa gaagggtgag 480

[1567] accgtatacg tgtcagctgc gtcgggagcg gtaggccaac ttgtgggtca gttcgcaaag 540

[1568] ttgacgggtt gttacgtggt tggcagtgca ggttccaaag agaaggtgga tctgcttaag 600

[1569] aataagttcg ggtttgacga ggccttcaat tataaggaag aggccgattt agatgccgcg 660

[1570] ttgcgtcgtt acttccccga tggtatcgat atctacttcg aaaacgtcgg cggtaagatg 720

[1571] ctcgatgccg tcctgccgaa tatgcgcccc aagggccgca ttgcggtttg cggcatgatt 780

[1572] tctcagtata atctggaaca accggaagga gttcgcaatt taatggcgtt gatcgtaaag 840

[1573] caagtgcgta tggaaggttt catggtgttc tcttattatc atctctatgg caagtttctc 900

[1574] gaaaccgtgc ttccatacat caagcaggga aagattacgt acgttgaaga tgtcgttgac 960

[1575] ggtcttgaca acgcaccggc ggcgctgatt ggtctctact caggccgtaa tgttggaaag 1020

[1576] caagtggtgg tggtctctcg tgagtga 1047

[1577] SEQUENCE ID (ID): 94

[1578] atgacggcca ccaacaagca agtgatcctg aaagactacg tttcaggttt ccccacggag 60

[1579] agcgactttg attttacaac tacgacagtg gaacttcgtg ttcctgaagg caccaactcc 120

[1580] gtcttggtta agaacttata tctgtcgtgc gacccctata tgcgcatccg catgggcaag 180

[1581] cctgacccta gcacagcggc acttgcgcaa gcgtataccc cgggccagcc tattcaaggt 240

[1582] tacggggtca gccgtatcat cgagtcgggg catccggact acaagaaggg cgacctgctc 300

[1583] tggggcatcg tagcatggga agagtatagc gtcatcaccc ctatgacgca cgcccatttc 360

[1584] aaaatccagc atactgacgt acctcttagt tattacacgg gtttgttagg catgcctggt 420

[1585] atgaccgctt acgcggggtt ctatgaggtg tgcagcccaa aagagggtga gacggtatac 480

[1586] gttagcgccg cgtcaggcgc agtcgggcaa cttgtcggcc aattagctaa gatgatgggc 540

[1587] tgctatgtag tcgggtctgc gggaagcaag gagaaagttg acctgctgaa gacaaaattc 600

[1588] gggttcgacg atgcgttcaa ttataaagag gagtcggatt taacggccgc gttaaagcgc 660

[1589] tgtttcccca atggaatcga catttacttt gagaacgttg gtgggaaaat gttagatgct 720

[1590] gttctggtta acatgaatat gcatggccgc attgccgtat gtggtatgat ctcacaatat 780

[1591] aatcttgaaa atcaggaagg tgttcataat ctgagtaaca ttatctacaa gcgcatccgt 840

[1592] attcaaggat ttgtcgtgag tgacttctac gataagtaca gcaagttcct cgaattcgtt 900

[1593] ctgccgcata ttcgtgaagg taaaatcacg tatgtagagg acgtcgcgga tggcttggag 960

[1594] aaagcgcctg aggccttggt gggcttattc catgggaaga atgtcggtaa gcaagtggtg 1020

[1595] gtagtggccc gcgagtga 1038

[1596] Sequence Listing (ID): 95

[1597] atggcggaag aggtatccaa taagcaggtc attctcaaga attatgtgac tggatatcct 60

[1598] aaggaaagcg acatggagat caagaatgta acgattaagt taaaggttcc tgagggtagt 120

[1599] aatgacgttg tggttaagaa cctctacctg tcatgcgacc cgtacatgcg ctcacgcatg 180

[1600] cgcaagatcg aagggtcata cgttgagagt tttgcaccag gaagccccat caccggttac 240

[1601] ggcgtcgcta aggtcctgga gtcaggagat ccgaaattcc agaaaggcga tttagtatgg 300

[1602] ggtatgaccg ggtgggaaga atattcgatt attaccccta cccaaaccct ctttaaaatc 360

[1603] cacgacaaag atgtgccttt atcatactac accggtattt taggaatgcc tggtatgacc 420

[1604] gcttacgctg gtttccacga ggtctgttca ccaaagaagg gcgagaccgt tttcgtttca 480

[1605] gcggcgagcg gcgcggtcgg gcaactcgtc ggtcaattcg cgaagatgtt aggatgttat 540

[1606] gtcgtcggta gtgcaggcag caaggagaaa gtagatctgc ttaagagcaa atttggtttc 600

[1607] gacgaggcgt tcaactacaa ggaagagcag gatttgagtg cggcgttgaa gcgttacttt 660

[1608] ccagacggca tcgatatcta cttcgagaat gtcggcggaa agatgctgga cgccgttctt 720

[1609] gtgaacatga agttgtatgg tcgcattgca gtatgtggca tgatttcgca atacaattta 780

[1610] gagcaaacag aaggcgtcca caatctgttc tgtctcatca cgaaacgtat ccgcatggaa 840

[1611] ggcttcctgg tcttcgacta ctatcacttg tatccgaagt acttggagat ggtaattcct 900

[1612] caaatcaagg cggggaaggt agtctatgta gaggacgtgg cgcatggctt agagagcgcg 960

[1613] ccgacagcac ttgtaggcct tttcagtggc cgtaatatcg gtaagcaagt agtcatggtg 1020

[1614] agccgcgagt aa 1032

[1615] Sequence number (ID): 96

[1616] atgggtcaac aaaagcaacg taaccgccgt tgggttctcg ctagccgccc tcacggtgcc 60

[1617] ccggtaccgg agaattttcg cctggaagag gacgacgtag ccactccggg tgagggtcaa 120

[1618] gtactcctgc gcacggttta cctgtcgtta gacccctata tgcgtggtcg tatgagtgat 180

[1619] gagcctagtt acagcccgcc ggtcgacatt ggtggtgtga tggttggtgg cactgtcagt 240

[1620] cgcgttgtcg aatctaatca tccagattac cagagtggtg actgggtgct tggctacagt 300

[1621] ggttggcaag attatgatat ctctagcggt gatgacctcg tcaagctcgg cgaccacccg 360

[1622] caaaatccta gttggagcct cggcgttctg ggtatgccag gctttacggc ctatatgggt 420

[1623] ctcctggaca tcggccagcc taaagagggt gagaccttag ttgtagctgc ggccaccggc 480

[1624] ccggtaggcg ctacggtagg ccaaattggc aaattgaagg gctgccgtgt tgtcggcgta 540

[1625] gcgggcggtg cagagaaatg tcgccacgcc actgaggtat tagggttcga cgtatgcctc 600

[1626] gaccaccatg ctgacgactt tgccgagcag ctcgcgaaag cctgccccaa gggcattgac 660

[1627] atttactacg agaatgtggg tggcaaggta ttcgacgccg tcctgcccct cttgaacacc 720

[1628] tctgctcgca tccctgtgtg cggcctcgtt agcagctaca acgccacaga gttaccgccc 780

[1629] ggtccggatc gtttaccgtt gttaatggcc acggtgctga agaagcgtat ccgtttacag 840

[1630] gggtttatca tcgctcaaga ttacggccac cgtatccacg agtttcagcg tgaaatgggt 900

[1631] caatgggtaa aggaagacaa gatccattac cgcgaggaga ttacagacgg gctggagaat 960

[1632] gcaccacaaa ctttcatcgg tctgttaaag ggcaagaatt tcggaaaggt cgtcattcgc 1020

[1633] gtcgctggtg acgattaa 1038

[1634] Sequence Listing (ID): 97

[1635] atggccccgg ttactaacgg ccgtatcatt tttaacagca ttccgaccgg cttcccggtt 60

[1636] ccgggcgaaa ccactatcta tgatacgacc gaaaccatcg atctggatac tgctccgctg 120

[1637] gatggcggtt tcctcctgaa aaccctggaa ctgtctgttg atccgtacat gcgtggcggt 180

[1638] atgcgcgcac cggaaaagaa aagctactcc gccccgttca ctctgggcca gccgctgcgc 240

[1639] ggctatggtg taggtgtggt tctgcgttcc gagaacccac aggtaaaggc aggtgaccac 300

[1640] ctgtacggct ttttcgagca cacccattat agcatccgta aggacctgac cggcctgcag 360

[1641] GCGATCGAAA ATGCA TAT AACC TGCCTTGGAGCGTTTCA TTGGCGTGAT CGGTATGCCA 420

[1642] GGTA AAAC TGC TTAC ATGGC GTGG AAAG AAT ATGC GCACC CGAAAC AGGG TGAAACTGTC 480

[1643] TTCGTTAGCAC TGGTGCTGGTCCGGTTGGCAGCTTTGTATCCAGCTGGC AAAAGCGGAT 540

[1644] GGTCTGAAGGT GATCGCGTCTGC GGGCTCT GAGGAAAAAG TTCAGTTCAT GAAAGAAGTT 600

[1645] GGCGCTGACG TAGCGTTCAA CTAC AAAACC ACTAACACTG CAGAAGTTCT GGAGAAAGAA 660

[1646] GGCCCGATCG ACATCTATTG G GACAACGTC GGC GGTGAGACTCT GGAAGCTGC GCTGAAC 720

[1647] GCAGCTAACG TGAACGCTCG CTT CATTGAA TGC GGC ATGATTTCTGGCTA CAAC TCCGGC 780

[1648] G GTGCTCCGGT GCGTAACATC TTCCACGTG AT TGGCAAATCC AT TACC AT G ACCGGTTTT 840

[1649] ATCGTATCTC GTATCGAACC GAAGTACTCT GCAGAATTCT ACAAAGAAGT ACCGGCAAAG 900

[1650] GTGGCGTCTG GC GAAC TGA AAT ATCGTGAAC AC GTTTACAAC GGTCTGGAGAAGCTGGGC 960

[1651] GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTGGT GCGTGGTgatgtcattc tggcagtcca gaaaggtgag aacaaagcaa aagcagttgt gcatgttgcc 1020

[1652] gatgactaa 1029

[1653] Sequence Listing (ID): 98

[1654] atggcgagcg tgaccaacgg ccgtgtgctc ttcaactcca ttccggaggg tttcccggaa 60

[1655] ccgggtaaaa cggtcgttta tgacacttct gaaaacatcg atctggacac tgttccgctg 120

[1656] aacggtggct ttctcctgaa gaccctggac ctgtccattg acccgtacat gcgcggtcgt 180

[1657] atgcgtgcac ctgaaaagaa aagctactct ccgcctttcc tcctgaacca gccgatcgat 240

[1658] ggctacggtg ttggcgtagt tctgcgttcc gaactgccgg aagtcaaggc tggcgaccat 300

[1659] ctgtatggct ttttcaagca cgttcagtac gacgtacgta ccaacctgga aggcctgtct 360

[1660] aaactgccga acgaacacgg tctgtcctgg tctgtgtatg taggtgctgc aggtatgcca 420

[1661] ggcaaaactg cgtatatggc gtggaaggaa tatagccagg caaagaaagg tgagactgta 480

[1662] ttcgtgtctg ctggtgcggg tcctgtaggt agcctggtaa ttcaatttgc gaaggctgat 540

[1663] ggcctgaaag tgatcggttc cgcaggttct gacgaaaagg ttcagttcat gaaagagtgc 600

[1664] ggtgcagacg tagcattcaa ctacaaaacc acgaacacca aggaagtcct ggaaaaagag 660

[1665] ggccctatcg atatcttttg ggataacgtt ggtggcgaaa ccctggaagc ggccctggag 720

[1666] gctgcgaacg ttaacgcgcg ttttattgag tgcggtatga tctctggcta caacagcggt 780

[1667] ggcgcgccga tccgtaacct gttccacgta gtgagcaaga gcatctctat gcacggcttc 840

[1668] atcgttagcc gtctggagcc gaaatatggt aaagaatttt acgaaaccat cccgcacaag 900

[1669] ctggcatctg gtgaactgaa acaccgtgaa cacgtctttg atggtctgga taaagtcggt 960

[1670] gaagcgctgc tcgccgttca gaaaggcacc aacaaggcga aagctgttgt gaaagttgct 1020

[1671] gatgagtaa 1029

[1672] SEQUENCE ID (ID): 99

[1673] atgaatccga agtataagcc attgtttgaa ccgtttacct tcaaaagcgg cgtcaccatt 60

[1674] aacaatcgta ttgccgtagc gccaatgact cactacgcct cgaatgagga cggcacgatt 120

[1675] tcagaggcgg agcttgatta catcatcccg cgcagcaagg agatgggtat ggttatcacg 180

[1676] gcgtgtgcca atgtcacccc cgacggcaaa gcgtttcctg gccaacctgc catccacgac 240

[1677] gactcgaata tccctggtct taagaagctg gcccaggcca ttcaagcgca aggcgccaag 300

[1678] gcggttgttc aaattcatca tggtgggatc gagtgtcctt ctgagttggt tccgcaacaa 360

[1679] gacgtggtgg gcccctctga cgtgtttgac aatggcaagc aaattgcccg cgcgttgacc 420

[1680] gaggaagagg ttgaaaacat tgtaaaggcc tttggcgagg caacccgccg tgcaattgag 480

[1681] gcgggattcg acggcgtgga gatccacggt gcgaacggct acttgatcca gcaattctac 540

[1682] tcgccgaaga cgaatcaacg cacagatcgc tggggcggaa gcgatgaaaa gcgcctcgct 600

[1683] ttccccttag cgatcgtaga tgaggtaaag aaagccgcat ctgaacacgc caagggcgcg 660

[1684] ttccttgtcg gttaccgttt gagccctgag gaaccagaga cacctgggct tacaatgact 720

[1685] gagacgtaca cactcgtgga cgccctcggt gacaaggagc tggactatct tcatatctca 780

[1686] ttgatggacg ttaattctaa ggcccgccgt ggtgcggatc ccacacgtac tcgtatggac 840

[1687] cttctgaacg agcgcgtagg aaataaggta ccgctgattg cggtgggctc aatccacagc 900

[1688] gcggacgacg cactggccgt cattgagaat ggcatcccac tggttgcaat gggacgcgag 960

[1689] attctggtgg accccaattg gacagtgaag gttaaggaag gtcgtgagaa gcaaatcgag 1020

[1690] acagtaatta aaggcacgga caaggaaaag taccatttgc cagagccgct ctggcaagcc 1080

[1691] attgtgaata ctcagggttg ggtaccgtat aaggactaa 1119

[1692] Sequence Listing (ID): 100

[1693] atgaacccaa aatataaccc actgttcgag gcttttaccc tgccgtctgg tgttaccctg 60

[1694] aagaaccgta tcactatggc cccgatgact aacttcgctt cccacgagaa cggcgaagtt 120

[1695] tccgacgaag agctggctta ttaccgcgaa cgtagcggcg gtgtcggtgc agtgatcacc 180

[1696] gcgtgcgtat acgttacccc ggacggcaaa ggcttcgtca atgaattctc tgcagataag 240

[1697] gacgaaatga ttccatctct gcgtcgcctg gccgacacta ttcaccagga aggcgctaag 300

[1698] gcaattctgc agatctatca cggtggccgc ctctgccctc cggatcaaat cccagatggc 360

[1699] cagccgattt ctgcaagcgc tgttgctgag gaaaaagaag gtgctccagt accgcgtgaa 420

[1700] atgacctctg atgacatcca ccgtgtaatc cgtgcgtacg gcgaggctac gcgccgtgcc 480

[1701] atcgaggcgg gttacgatgg tgttgagctg cacggcgcga acggttacct ggtgcaacag 540

[1702] tttttctccc cgcactctaa catccgtacc gacgaatggg gtggctccct ggaagagcgt 600

[1703] ctgactttcc cgctggccgt ggttcacgaa gttaaaaagg ttatcgctga acatgcgaaa 660

[1704] cgtccgttca tctttggcta ccgcctgagc ccggaggaag gccacactcc aggcatcacg 720

[1705] ctggatgaca ctatggttct ggttgatcgt ctggcagatg agggcctcga ctatctgcat 780

[1706] atctctgtaa accacttctt tggcggttcc ttccgtgatc gtagcgacga gcgttcccgt 840

[1707] accgttctga ttcacgaaaa agtgggcaac cgtgttccag tgatgggtgt aggtagcctg 900

[1708] aataccccgg acgaggcact ggcggcactg gaaaccggcg tgccactggt atctctcggt 960

[1709] cgcccgctcc tgatggaacc gcagtgggtt cagaaagtcc agaacggtac tgaggacacc 1020

[1710] atccgtacta ccctgagcaa acaggcgcag caagagctgg ttatcccgga ttacctgtgg 1080

[1711] ggcgctctga cgactatccc gggctggatg ccggtaactg attaa 1125

[1712] SEQUENCE ID (ID): 101

[1713] atgaataccg agctgctttt caaacctttc aaggcgggta acttatcgct tcccaatcgc 60

[1714] atcgttatgg cccccatgac acgtaatttt agccctcaag gtatcccggg cccggaagtt 120

[1715] gcggcctact accgccgtcg tgcagaaaat gcggtaggtc tcattatcac cgagggtacg 180

[1716] GCGATTAATC ATCCCGCCGC TGTCGAGCAC ACCTCAATCC GAACTTCTAC GGC GAGGGC 240

[1717] CTTGAGGGAT GGGCAAAGGT CGTCGAGGAA GTCCATGCGG TAGGCGGGAA GATTATTCCT 300

[1718] CATGAATTGT GGCATGTCGG CACCgCTCGC AAGATTGGCG CCgACAACCA GCCGAACTC 360

[1719] GAAGCCCTGC CTGTAAGCCC TTCGGGTATT AGCCCggCGG TGAAAAGGT GGTGGAGCCC 420

[1720] CTCACCgAGG CCgAAATCGC GGACATTATT AGTGCCTACG CCAAGCCGCG GCTGATGCA 480

[1721] CAACGTGTTG GGTTCGATGG GATCGAGCTG CACGGCGCAC ACGGATACTT AATCGATCAA 540

[1722] TTCTTTTGGG ACAAGACAAA TAAGCgTACG GACCAATACG GCGGGAATTT GGTGCAACGT 600

[1723] ACCCGCTTTG CAGTGGAAgt TATCGAGGCG TGTGCCCgCG CCgtTgGTCC GAATTTTCCA 660

[1724] ATCgtTCTTC GTTTCTCACA ATGGAAGATG TACCATTACG AGGAGAAGCT CGCTCAAACT 720

[1725] CCTCAAGAGT TGGAGCAATT CTTGACCCCC TTGgtTAAGG CTGGAGTAGA CATCTTTCAC 780

[1726] tgcagctcac gccgcttctg ggaaccggag ttcgagggta gcgatctgaa cctggcggcc 840

[1727] tggaccaaga agattaccgg aaagcctgta atcactgttg gaagcattgg ccttgagaag 900

[1728] gcctttctca gcgatttaga gaagaacaat aatcgtcaga ccgaccaatc aagctctgta 960

[1729] gaagcccgtt tggagcaatt agtcggtcag gtggagcgcg aagaagctga tctggtggcc 1020

[1730] gttggacgcg cgcttcttgt tgacccggcg ttcgccgtga aactccgcga ccaacagatc 1080

[1731] gaagagatca tcccttacag tgatgaggtt ttaaagacac tcaactaa 1128

[1732] Sequence Listing (ID): 102

[1733] atgaatacca tgcttttcag tccctatact attcgtggtt tgacacttaa gaaccgtatc 60

[1734] gtcatgagcc ctatgtgcat gtactcctgc gacacgaagg atggcgccgt acgcacgtgg 120

[1735] cacaagattc attacccggc acgcgccgta ggccaagtgg ggctgattat tgtggaagcg 180

[1736] actggagtga cccctcaagg acgtatctcc gaacgcgact tgggcatttg gagcgatgac 240

[1737] cacattgcgg gacttcgcga gctggtcggt ctggtgaaag agcatggagc ggccatcggc 300

[1738] atccagctgg cgcatgcggg acgcaaatcg caagtcccag gggagatcat cgctcctagc 360

[1739] gcggtacctt ttgacgacag tagtccgacc cctaaagaga tgactaaggc ggatatcgag 420

[1740] gagacggtac aagcgtttca gaatggtgcc cgccgtgcta aagaggccgg cttcgatgtc 480

[1741] attgagattc atgcggcgca cggttacctg atcaacgagt tcctgtctcc tctgagcaat 540

[1742] cgtcgccaag atgaatatgg cgggtcgccc gagaatcgct atcgttttct tggggaagta 600

[1743] attgatgccg tgcgtgaggt gtgggatggc ccattattcg tacgtatcag cgcatcggac 660

[1744] tatcatccgg acggtttgac tgctaaagac tacgtaccct acgcaaagcg tatgaaggaa 720

[1745] cagggagtag acttagtgga cgtgtccagc ggcgccatcg tcccagcccg tatgaatgtc 780

[1746] tacccaggtt atcaagtgcc atttgcggag ctgatccgtc gcgaggccga cattccaacc 840

[1747] ggcgcggttg ggttgattac gtctggctgg caagccgaag aaattctgca aaacggtcgc 900

[1748] gcggacttag tgtttctggg acgcgagttg ttgcgtaatc cttactggcc ttatgcggca 960

[1749] gcccgtgagc tgggagccaa gatctcggcc cccgtccaat atgagcgcgg ctggcgtttc 1020

[1750] tga 1023

[1751] Sequence Listing (ID): 103

[1752] atgaccggca aactgttcag cccgatctct gttggcccgc tgtctctgcc aaaccgtatc 60

[1753] tttatggctc cgctgacccg tatgcgttct cgtgaacctg gtgacgttcc ggttctgccg 120

[1754] ctgatggctg agtactatcg tcagcgtgct aacgcaggcc tgatcattag cgaagcaacc 180

[1755] caggttagcc cgcagggtaa aggttacatg ggcactccgg gtatccacag cgctgaacag 240

[1756] gttgaagcgt ggcgcgacat tactcgtgca gttcatgacg aaggcggtca cattgctatt 300

[1757] cagctgtggc atgtcggccg tgtttcccat cactctctgc agccggatcg ccagctcccg 360

[1758] gtgtctgctt ccgccatccc gtatgagaac aaaactacca ttcgtggcga agatagcaaa 420

[1759] ccgcaacgtg ttgcttgcga taccccgcgc gctctgcgta ctgatgaaat tccgggtctg 480

[1760] atcgaaactt accgtcaagc cacgatcaac gcgcgcgaag caggtttcga cctggttgaa 540

[1761] gttcacgcag cgcacggcta cctcctgcac caattccagt ccgccgtgtc taaccaccgt 600

[1762] gatgacgctt atggcggttg cctggaaaac cgcgcgcgtc tgactctgga ggttgtggac 660

[1763] gcctgtattg cggcatggga cgcagcgcat gtcggtatcc gtatctcccc gctgggtacc 720

[1764] ttcaacggcc tggatgactc cgctggtctg gaaatgggtc tgtatctggc cgaacagctg 780

[1765] gcgaaacgta atatcgccta cctccacctg tccgaaccgg actgggctgg cggtccggct 840

[1766] cactccgatg aattccgcca ggctctccgt gatcgtttcc ctggtgtcat tatcggcgcg 900

[1767] ggtaactata ccgttgaaaa agccgaagca ctgctcgcaa agggctatat cgatgccgct 960

[1768] gcattcggtc gtccatacat ctccaacccg gatctggcgg aacgtttccg caccggtgca 1020

[1769] GCGCTGGCTA TGCTGAACCC GGCCACCCTG TACGGTGGCG GTGAGGAAGG TTATACC AAC 1080

[1770] TACCCGGCCC TGGCCTAA 1098

[1771] SEQ ID NO: 104

[1772] ATGTCCGGTA AACTGTTCAC CCCG GTTACC ATCGGTGGCT TC ACTCTGCC GAACC GC GTT 60

[1773] CTGATGGCGC CGCTGACTCG TATGC GCTCTTCCC AGCCGGGTGA CGTGCCGAAC GAAC TG 120

[1774] ATGCAAGCGT ACTATGTCAG CGTG CATCCGCAGG CATGATTATC G CAGAAGCTAC TC AG 180

[1775] ATTTCCCCAC AGGGTAAGGG TTATATGGAT ACCCCTGGCA TCT ACTCTGCAG AACAGGTT 240

[1776] GC GGGTTGGAAG AAAATTACC AAGCAGTTCA TGAAGCGAAC GGCCACATCT GCCTGCAG 300

[1777] CTGTGGCATG TTGGTCGTGT GTCTCATCAC TCCCTCCAGC C GGATCAACAG CTGCCTGTG 360

[1778] TCCGCTAGCG CGATCCCATA CGAAAACCGC ACTACC GTGCGTG GTGAAGACGG TAAAGTG 420

[1779] AAACGTGTTC GTGC GATACC CC GCGCGCCC TGG AACTGACTG AAATCCC GGGTCTGATC 480

[1780] GAAGATTACC GCCGTGCCAC TGTA AACGC GCGAAGCAGGCTTCGATAT GGTGGAAGTT 540

[1781] CACGC GGCTC ACG GTTA CCT CCTGC ATC AGTTCCAGTCCGCAACCTCCAA CCAGCGCAAC 600

[1782] GACGCTTATGGTGGCAGCCTGGAGAACC GCGCGC GTCTGACCCTGGAAGTTCTGGACGCT 660

[1783] GT CATCGGTGCTTGGGACGCTGCACACGTGGGTATCCGTATCTCCCCGCTGGGTATTTTC 720

[1784] AACGGCCTGGACGATCGTGACGGTCTGGACATGGGTCTGTACCTGGCTGAACAGTTCGCT 780

[1785] CTGC GTGGTATTGGTTACCTGC ATCTGTCTGAACC GGATTGGGCCG GTGGCCCTGTTC TG 840

[1786] AATGAAGAGTTCCGCGTAGC ACTCCGTGCACGTTTCCC GG GTATTATCAT TGCAGCCGGT 900

[1787] A ACTACAGCGTAGAAAAGGC AGAAGGCCTCCTGGAAAAAGGTCTGATCGATGCCGCGGCC 960

[1788] TTCGGTCGCCCGTT CATCGCAAACCCGGACCTGCCGCAGC GTCTGCGTAAAGGC GC GGAA 1020

[1789] CTGAATGCAGTTAACGCAGCGACCCTGTATG GTGGCGGTGCGGAAGGCTACACCGACTAC 1080

[1790] CCGGC ACTGG CCTAA 1095

[1791] SEQUENCE ID (ID): 105

[1792] atgtcgggta agctgtttac acccttttcc tcgggctctt ttacattccc taaccgtgta 60

[1793] atcatggcac ccttgacccg tatgcgtgcg tcgcagccgg gtgacattcc caacgagctt 120

[1794] atgcaaactt actatgtaca acgcgcgtct gccggattaa tcatcgcaga ggcgactcag 180

[1795] atctctcctc aggggaaggg ctacatggac acaccgggta tctatagcgc cgagcaagtt 240

[1796] caaggctggc gcaagattac gcaagcagta catgaggccg gtggtcacat tgctctgcaa 300

[1797] ctgtggcatg tcggtcgcgt atctcaccac tccttgcaac ctgatcaaca gcttcccgta 360

[1798] tcagcgtcag ccattcccta ccaaaatcgc acaactgttc gcggtgagga cgggaaacca 420

[1799] acacgcgtgg attgtgatac cccgcgtgcg ctggagttaa gcgagattcc gggcgttatt 480

[1800] gaagactatc gccgtgcaac ggttaatagt cgcgaggccg gttttgacat ggttgaagtg 540

[1801] catgccgccc acggttattt acttcatcag tttcaatcgg ccgaatcaaa caagcgcgag 600

[1802] GATGCATCGG CGGAGTTTAG AGAACCAGCG CGCCTTAACC CTGGAAACCT TGGACGCC 60

[1803] GTTATCGGAG CGTGGGACGC GAAGCACGTC GGGATTCGCA TCAGCCCTCT GGGTACTTTC 720

[1804] AACGGTCTGG ATGACAAAGA TGGCTTGGAA ATGGCCTCTA CTTCACGCAC GAGTTTACG 780

[1805] AAGCGTGGAA TTGCCTACCT TCACCTCTCT GAGCCGGACT GGGCGGGCGG CGCCTAC 840

[1806] GGAGATGATT TTCGCCAGGC ATTGCCTGAC GCCTTTCCCG GTACCATCAT CGGGGCGGGA 900

[1807] AATTACACTG TGGAAAAGTC TGAGATGCTT CTTGCCAAGG GCTTTCATCG ACGCTGCAGC 960

[1808] TTTGGACGCC CGTTTTCATC GCAGAACCCT ACCTTCCCGT ACGTCTGCAA AAGGGCGGAG 1020

[1809] TTAAACAATG TAGTGGCCGC TACACTCTAC GGGGGGGGTG CCGAGGGCTA CACAGACTAT 1080

[1810] CCAGCGCTGG CCTGA 1095

[1811] SEQUENCE ID (ID): 106

[1812] ATGAAACTGC TCCAGCCGCT TCAGATTGGT CCCTAACCCT GCCTAACCCT GTTTTATG 60

[1813] gcacccctca ctcgtcttcg ctcactggag ccgggcgatg tcccgaccac tctgatgggt 120

[1814] gaatattatc gccagcgtgc cagcgccggc cttatcatca ccgaagcgac ccaaattagc 180

[1815] tttcaagcaa aaggttacag tggtagcccc gggatccact ccgcagaaca aattgctgcg 240

[1816] tggaaacaca tcaatgaagg cattcatgct gacggcggtc acagcgcggt tcaggtgtgg 300

[1817] cacacgggac gcgtcagcca cacttcactg cagccaggcg gagaagcacc tgttgcaccc 360

[1818] tcggcactgc cagctggggc gcgtacgact cttcgcgacg aacagggtga tcttattcgt 420

[1819] gtggaaacta gcgccccgcg cgccttgtcg gaagctgaga tcgcgggtat tgtggcggat 480

[1820] tttggactcg cggcgattaa tgcgcgtgaa gcgggatttg atttcattga actgcatgct 540

[1821] gcacatggct acttactgca ccaatttctt actccttccg caaatcagcg cgaagatcgt 600

[1822] tacggcggct ccgtggagaa ccgcgcccgt attgtcctgg aagccgtaga tgcggcggta 660

[1823] gccaactggt ctgccgaacg cgtagggatc cgcgtctttc ccttaggtgg gttcaacggc 720

[1824] gtagacaatg gggaagatca ggaagcggcc ggcctgtact taattcgtga actggccaaa 780

[1825] cgtaacttag cgtacctgca tctgtctgaa ccagactggg cgggcggtaa accgcttcgt 840

[1826] gatgagtttc gccaagccat tcgcgcagca tatccgggag taattatcgc cgccggggcg 900

[1827] tacaccgccg agaaaggcga ggaccttatc ggtcgcggcc tcatcgatgc cgtagccttt 960

[1828] ggtcgttcgt atatcgcaaa tccggacttg gtggaacgtt tacgtcttca agcgccgtta 1020

[1829] aacgaacacc gcgcgcagtt tgattacgcg aatggcccgg aaggatatac cgattatccc 1080

[1830] ttccttaaac aggcctaa 1098

[1831] Sequence number (ID): 107

[1832] atgtctagcg aaaaactgta ctctccgctc aaagtcggtg caatcaccgc cgcgaaccgt 60

[1833] atcttcatgg ctccgctgac ccgtctgcgc agcatcgaac cgggcgatat cccgaccccg 120

[1834] ctgatggcag aatattaccg ccagcgtgct tctgctggcc tgatcatttc cgaggcaact 180

[1835] cagatctccg ctcaggcaaa aggctacgcg ggcgcgccgg gcatccactc cccggaacaa 240

[1836] atcgcagcgt ggaagaaaat taccgctggt gttcacgcag aaaacggtca catggcagtc 300

[1837] cagctgtggc atactggccg catctcccac gcgtccctgc agccgggtgg ccaagcccct 360

[1838] gttgctccgt ctgcgctgag cgccggtacc cgtactagcc tgcgtgacga aaacggccag 420

[1839] gctatccgcg tcgaaacctc tatgccgcgc gccctggaac tggaggaaat cccaggcatc 480

[1840] gttaacgact tccgccaggc gatcgcgaac gcgcgtgaag ctggtttcga tctggttgaa 540

[1841] ctgcacagcg cgcacggcta cctcctgcac cagttcctgt ctccgtctag caaccaccgc 600

[1842] actgaccagt atggcggtag cgtggaaaac cgtgctcgcc tcgttctgga agtggttgat 660

[1843] gcgggcatcg aggaatgggg cgccgatcgt attggtatcc gtgtcagccc gattggcacc 720

[1844] tttcagaaca ccgataacgg cccgaacgag gaagcggacg ctctgtacct gatcgagcag 780

[1845] ctgggtaaac gtggtatcgc gtatctgcac atgtctgagc ctgactgggc aggcggtgag 840

[1846] ccgtacaccg atgcattccg cgagaaagtt cgcgctcgtt ttcacggccc aatcattggt 900

[1847] gcgggcgcgt acaccgtcga gaaggcggaa actctgattg gcaagggcct gatcgatgcg 960

[1848] gttgcattcg gccgcgactg gatcgcgaac ccggatctgg tagcgcgcct gcagcgtaag 1020

[1849] gctgaactga acccgcagcg tgctgaatcc ttctatggtg gcggtgcgga gggctacacc 1080

[1850] gattacccta ccctgtaa 1098

[1851] Sequence number (ID): 108

[1852] atgagcgctg aaaagctgtt cacccctctc aaggttggtg ctgtaaccgc gccgaatcgt 60

[1853] gtcttcatgg cgccactgac tcgtctgcgt agcatcgaac ctggcgacat cccgaccccg 120

[1854] ctgatgggtg agtattaccg tcagcgcgcc tccgcgggcc tgattatctc cgaagcgacc 180

[1855] caaattagcg cgcaagcgaa aggctacgcg ggcgcgcctg gtctgcactc cccagaacag 240

[1856] atcgccgctt ggaagaaaat taccgctggt gtgcatgccg aagatggtcg tatcgcggtt 300

[1857] caactgtggc acaccggtcg catcagccat tcctctattc agccgggcgg tcaggctccg 360

[1858] gtttctgcat ctgctctgaa cgcgaacact cgtacctctc tgcgtgacga aaatggtaat 420

[1859] gctattcgtg ttgacaccac gactccgcgt gctctggaac tggatgaaat tccgggcatc 480

[1860] gtaaacgact ttcgtcaagc ggttgcaaac gcacgtgaag caggcttcga tctcgtcgaa 540

[1861] ctgcatagcg ctcatggtta tctcctgcac cagttcctgt ctccgagctc caaccagcgc 600

[1862] accgaccagt acggcggtag cgttgaaaac cgtgcgcgtc tggtactgga agttgtagat 660

[1863] gccgtttgca acgaatggtc cgctgaccgt atcggtatcc gtgttagccc tatcggcacc 720

[1864] tttcagaacg tggataacgg tccgaacgag gaagcggacg ctctgtacct gatcgaggaa 780

[1865] ctggctaaac gcggtattgc atacctccac atgtctgaaa ctgatctggc aggcggtaag 840

[1866] ccgtattctg aggctttccg tcagaaagtt cgcgagcgct tccacggtgt aattatcggc 900

[1867] gctggtgctt acaccgcaga gaaagcagaa gatctgatcg gcaagggtct gattgatgct 960

[1868] gtggcctttg gccgtgatta catcgccaac ccggacctgg tggcacgtct gcagaagaaa 1020

[1869] gctgaactga acccgcagcg cccggagagc ttctatggtg gcggtgcaga aggttatacc 1080

[1870] gattacccgt ccctgtaa 1098

[1871] Sequence number (ID): 109

[1872] atgaaaaccg ctaagttatt ttctcccctc aaggtcggtg cgctgaccct gcccaatcgc 60

[1873] gtgtttatgg cccccttgac gcgtttgcgc tctattgagc caggtgatat cccgacccct 120

[1874] ttaatggcgg agtactatcg tcaacgcgca agcgccggcc tcatcatcac tgaggctacc 180

[1875] cagatcagct ttcaggccaa ggggtacgca ggcgcaccgg ggcttcacac acaagaacaa 240

[1876] ttaaatgcgt ggaagaagat tacgcaagcg gttcacgagg agggaggtca tattgcggtc 300

[1877] caattatggc acgttggccg cattagtcac tcaagcctgc aacccggtca lcaggcaccc 360

[1878] gtggccccta lcgctattgc tgcagacacc cgtaccaccg ttcgtgacga aaacggcgca 420

[1879] tgggtacgtg tgccatgctc tacaccgcgc gcattagaga cggaagagat cccgggcatc 480

[1880] atcaacgatt tccgtcaggc gactgctaat gctcgtgagg ccggattcga ctatatcgaa 540

[1881] ctccacgccg cgcacggtta tctcctgcac caatttatgt cacccgcctc aaaccagcgt 600

[1882] actgaccaat atggcggtag tattgagaac cgcactcgct taactttaga ggttgtcgat 660

[1883] gcgacggccg cccagtggtc agcagagcgc attggtatcc gtatcagccc acttggaccc 720

[1884] ttcaacggtc tggataacgg tgaagaccaa gaggaagctg ccctgtacct gatcgacgag 780

[1885] ctgaataagc gccatattgc atacttacat atctctgagc ccgactgggc gggtggcaag 840

[1886] ccttattcag aggcgttccg cgatgctgtg cgcgcgcgct tcaagggcgt gattatcggg 900

[1887] gcgggagctt ataccgcaga gaaagccgaa gaattaattg agaaaggctt tatcgacgcc 960

[1888] gtagcatttg gacgcagcta cattagcaat cctgacctgg tggcacgctt gcagcaacac 1020

[1889] gcgcccctga atgaacccga tggtgagacg ttttatggtg gcggggctaa gggttacacc 1080

[1890] gactatccaa ccctttga 1098

[1891] Sequence Listing (ID): 110

[1892] atgaaaaccg ccaaactgtt ctctccgctg aaagtgggtg cgttcaccct cccgaaccgc 60

[1893] gttttcatgg cacctctgac ccgtctgcgt tctattgaac caggcgatat cccgaccccg 120

[1894] ctgatggcag aatattacgc gcagcgtgcc tctgcaggcc tgatcattac tgaagccacc 180

[1895] caagttagct tccaggcgaa aggttacgcg ggcgcgccgg gcctgcacac ccaggaacag 240

[1896] ctggaaggtt ggaagaaaat cacccaggca gttcacgaga aacaaggcca tattgctgtt 300

[1897] CAGCTCTGGC ATGTGGGTCG CATTTC TCA TC ACTCTCTGC AGCCTAACCA GCAAGCACCA 360

[1898] GTTCGTTGCT CC GAGCGCCAT CGCGGCTGAT ACCCGCACCA CGATCCGCGAT GAAATGGTGAT 420

[1899] TGGGTCCGCG TCCC GTGTAG CACTCCGCGC GC ACTGGAAC TGCAGGAAAT CCCGGCTATC 480

[1900] GTCGATGACT TCCGCAACGC CACC GCA AACGCACGC GAAGCAGGTTTC GACTTCAT TGA A 540

[1901] ATCCATGCAG CGCATGGTTA CCTCCTGCAT CAGTTCATGT CTCCGGCGTC TAACCAACGC 600

[1902] ACTGACGCAT ACGGCGGTTC TATTGAAAAC CGCACCCGTC TGACTCTGGA AGTTGTCGAC 660

[1903] GCAACTGCCG CTGAA TGGGGCGCGGAGCACATCGGTATCCGTATCTCTCCGCTGGGCCCG 720

[1904] TTTAACGGCC TGGATAACGG C GAAGACCAG GAGGATGCAG CTCTGTACCT GATTGATGAA 780

[1905] CTGAATAAAC GCAAAATTGC CTACCTGCAC ATCTCTGAAC C GGACTGGGCT GGTGGCAA A 840

[1906] CCGTATACC GACGCTTTCC GTGATGCGGT GC GTGCACGTT TCAATGGCAT TATCGTGGGT 900

[1907] gctggtgcct acaccgccga aaaagccgaa actctgatcg aaaaaggttt catcgacgct 960

[1908] gtcgcttttg gtcgtagcta catcgcgaac ccggacctgg tcgaacgtct gcagcaacag 1020

[1909] gctccgctga acaccccgga cggcgatacc ttctacggcg gtggcgcgaa aggttacacc 1080

[1910] gattatccga ccctgagcta a 1101

[1911] Sequence Listing (ID): 111

[1912] atgacttctc tcttcgaccc tctgaagatt ggcgacatcc agctggcgaa ccgtatcgtc 60

[1913] atggcgccgc tcactcgtaa tcgttctcct ggcgctgtac caaacaccct gaatgcagct 120

[1914] tattacgagc agcgtgcctc tgcaggcctc ctgatcaccg aagcaacggc aatctctcac 180

[1915] cagggccagg gctacgccga cgttccgggt ctgtataaac cagaggcgct ggagggttgg 240

[1916] aaacaggtga ctgacgctgt gcataaagcg ggtggcaaaa tcgtggtcca aatgtggcac 300

[1917] gttggtcgca tctctcacga caccctgcag ccgaacggtg gcaagccggt tgccccgtcc 360

[1918] gctatccgcg ctaaaagcaa aacgtacctg attaatgctg atggtactgg tagctttgca 420

[1919] gaaacctctg agcctcgtgc cctggaaaaa gacgaactgc cgggcattat cgaagattac 480

[1920] cgccgtgcgg cacgcgcagc cgtcgacgcg ggtttcgatg gtgttgaaat tcacgccgca 540

[1921] aacggttacc tcctggatca gtttctgcgc tccggttcta acgaacgtac tgatgaatac 600

[1922] ggcggttcca ttgaaaaccg tgcgcgcctc ctgttccaag ttgtggatgt tatcaccaaa 660

[1923] gaaattggcg cgggtcgcac cgcaattcgt atttcccctg tgaccccagc gaacgacagc 720

[1924] tctgatccga acccacaacc gctcttcacc tacgttgtgg aaggtctggc aaaatatgat 780

[1925] ctggcttaca tccacattat cgaaggtgcg acgggtggcc cgcgtgacca ccaacagggt 840

[1926] gacgccccgt tcgactacgc ggccctgcgc gccgcttacc aggcagccgg cggtaaagca 900

[1927] gcttggatgg ttaataacgg ctacaaccgc gagctggcga ttgacgcggt agaggaaggc 960

[1928] aaagcagacc tggtggcatt cggcaaactg ttcatcgcga acccggatct ggtagagcgt 1020

[1929] ctgaaaaacg acaccgtgct gaacccaccg gaccaggcga ccttctacgg cggtggcgcg 1080

[1930] aaaggctaca ccgattatcc ggcactggaa aacgtggctt aa 1122

[1931] Sequence number (ID): 112

[1932] atgaccaaac tgttcgaacc ggcacaggcg ggtgatatcg cactggcgaa ccgcatcgtc 60

[1933] atggctcctc tgacccgtaa ccgttctcct ggtgcgatcc ctaacaatct gaacgcggca 120

[1934] tattacgagc aacgtgcgac cgctggtctg atcgtaaccg aaggcacccc ggttagccag 180

[1935] caaggccagg gttacgcaga tgtaccgggc ctgtataaac aggaagctat cgacggttgg 240

[1936] aaagcagtaa ccgatggcgt ccataaggct ggcggtaaaa tcgtagcaca gatctggcac 300

[1937] gtgggccgta tctcccacac ctctctgcag cctcacggtg gccaaccggt ggccccatct 360

[1938] cctattaaag cgaattccaa aacttatatt atcaacgacg atggcaccgg ctccttcgcc 420

[1939] GAAACTTCTG AACCgcgcga aatcagcctg caagaaattc cggtaatcct ggaggactac 480

[1940] CGTACTGGCG Cgcgtgcggc tattgatgcg ggttttgacg gcgttgaaat ccacgctgcc 540

[1941] AACGgttacc tgattgatca gtttctgaaa tctggcacca atcaacgtac ggacgcgtac 600

[1942] Ggtggctcca tcgagaaccg tgcgcgcttt ctcctggaag tagtcgacac cgtgactaaa 660

[1943] GAAATCggtg cgggccgtac tggtatccgc ctctccccgg tgaccccggc taatgacatc 720

[1944] TTcgaggcgg acccgcagcc actgttcgaa tatgtggctc gtgaactggg cagccgtggc 780

[1945] CTggcgttca ttcacgttat cgaaggcgct accggtggcc cgcgcgattt caaacagggt 840

[1946] GACAAACCgt tcgactatga cgccctcaaa gccgcgtata ctaatgccgg cggtaaaggt 900

[1947] CTgtggatcg cgaataacgg ttatgatcgt gaatccgcga tcgctgcgac cgaatctggc 960

[1948] AAAGTTGATG CCgttgcgtt tggcaaggcc ttcatctcta acccggacct ggtgcagcgt 1020

[1949] ctgaaagaaa acgctgcgct gaatgaaccg aaccaacaga ctttctatgg cggtggcgcg 1080

[1950] gaaggctaca ccgactaccc ggcgctggca taa 1113

[1951] SEQ ID (ID): 113

[1952] atgtctgatc tgttcgagcc gactaaggcc ggcgacatcg ccctggcgaa ccgtattgct 60

[1953] atggcgccgc tgactcgcaa ccgttccccg ggtgaagcgc ctaacgatct gaacgttact 120

[1954] tattaccaac agcgcgcgac tgccggcctg atcattactg agggcacccc tatcacccac 180

[1955] cagggtcaag gctacgctca cgttccaggc ctgtacaaac cggaagcact ggaaggctgg 240

[1956] aagaaagtga cggatgctgt tcacaaagct ggcggtaaaa ttgttaccca gatttggcac 300

[1957] gttggtcgtg ttagccacac ctctctgcag ccaggtgaag gcaaacctgt agcaccgagc 360

[1958] gcaatcaccg caaaatctaa aacctatatt atcaaccctg atggcagcgg tgccttcgca 420

[1959] gatacttctg aaccgcgtgc tctgtccctg gaggaaatcc cgggcatcct ggaagattac 480

[1960] cgcgttgccg cgcgcgctgc ggtcgacgcc ggcttcgacg gtgttgaaat ccacgctgcg 540

[1961] aacggttacc tcctggatca gttcctgcgt tccggctcca accagcgcac cgacgcgtac 600

[1962] ggtggctcta ttgaaaatcg tacccgtctg actctggaag ttgcagctgt tgtcgcgaaa 660

[1963] gaaatcggtg gcggtcgtac tggcattcgt atctctccgg taaccccggc taacgacgta 720

[1964] ttcgatccgg aacctcagcc gctcttcaat catctggttt ccaaactggc tggcctggat 780

[1965] ctggcattca tccatgtaat cgaaggtgcc accggtggcc cgcgtgactt caaacagggt 840

[1966] gataaaccat tcgattggga cgaactgcgt aaaacttatc gtgacgccgg tggcaagggt 900

[1967] gcatggatgg ttaataacgg ttacgacaag gcttctgcga ccgaagctgt ggcgtctggt 960

[1968] cgcgcggaca ttgtgacttt tggcaagctg ttcattgcta acccggacct ggtacgtcgc 1020

[1969] ttcaaggaag atgccccgct gaacgaaccg aacaaagcta ctttttacgg cggtggcgct 1080

[1970] gaaggttata ccgactaccc tttcctgccg taa 1113

[1971] Sequence Listing (ID): 114

[1972] atgcctaccc tgtttgatcc gctgaccctc ggtgatctgc agagcccgaa ccgtgtgctc 60

[1973] atggccccgc tgacgcgtgg ccgtgcgacc cgcgagcatg tacctaccga actgatgatc 120

[1974] gaatactata ctcagcgtgc gtccgcgggt ctgattatca ccgaagccac tggcatcact 180

[1975] caggaaggtc tgggctggcc gtacgcaccg ggtatctggt ccgacgaaca ggtcgaagcg 240

[1976] tggaaaccgg tcacccaggc ggtacatgag gcaggcggtc gtattatcct ccaactgtgg 300

[1977] cacatgggcc gtaccgtgca cagctccttc ctgggcggtg ctaaaccggt atcttcctct 360

[1978] gccacccgtg ctccgggcca ggcacatacc tacgaaggta aacaggacta cgacgaggca 420

[1979] cgtcctctca gcgctgatga aatcccgcgc ctgctcaatg actacgagca cgcggctaaa 480

[1980] aacgctatgg ctgcgggttt cgacggcgtt cagattcacg cggccaacgg ctatctgatc 540

[1981] gaccagttcc tgcgcgataa ctctaacgtt cgtggcgacg cttacggtgg ctccattgaa 600

[1982] aaccgcatcc gcctcctggt agaagtgact cgccgtgtag cggaaacggt gggtgctgaa 660

[1983] aaaactggtg tgcgtctgtc tccaaacggt gattcccagg gcgtgaacga ctctaatccg 720

[1984] gagccgctgt tctctgccgc agcgaaagca ctggatgaga ttggcatcgc gcatctggaa 780

[1985] ctgcgcgaac caggttacga gggtacgttc ggcaaagcag accgcccacc ggtacacccg 840

[1986] gtaatccgtc aggctttcag ccgtacgctg attctgaact ccgactacac cctggaaacc 900

[1987] gctcaagcgg cactggctac tggtgaagcg gacgccatca cctttggccg tccgttcctg 960

[1988] gcgaacccgg atctgccgca ccgcttcgct gaacgtctgc ctctgaacaa agatgttatg 1020

[1989] gaaacctggt actctcaggg cccggaaggc tatgtggact acccaaccgc cgaccagaaa 1080

[1990] taa 1083

[1991] Sequence Listing (ID): 115

[1992] atgcctaccc tgtttgatcc gatccgtctg ggtgcggtta ccgctaaaaa ccgtatcctc 60

[1993] atggcgccgc tgacccgtgg tcgcgcgacc cgtgaccatg ttccaaccga catcatgatc 120

[1994] aaatattacg cccagcgtgc atctgcaggt ctgattatct ctgaagccac cggcattagc 180

[1995] caagaaggtc tgggttggcc ttacgcaccg ggcatctgga acgaagccca gacccaggcg 240

[1996] tggatcccga tcacgcaggc ggtgcacgac gctggcggtc tgattttcgt gcagctgtgg 300

[1997] cacatgggcc gcctcgtacc gtcttccgtt tctggcatgc agccagtgag cgccagcgcg 360

[1998] actaaagccc cggatctggc tcatacttac gaaggtaaga aacctttcga cgtcgctcgt 420

[1999] ccgctggaga tcgcggaaat cccgcgcctc ctggatgact acgagcgtgc gacgcgtaac 480

[2000] gcgctgtccg caggcttcga cggcgtccag atccatgctg ccaacggcta tctgattgat 540

[2001] gaatttctgc gcgacggcac gaacctgcgc aaagatgcat acggtggcac tccggaacac 600

[2002] cgcatccgcc tcctgcgtga agtgactgaa cgtgtaatct ccgttatcgg tgcagatcgc 660

[2003] acttccgtgc gcctgtctcc aaacggtgaa attcaaggcg catctgatag ccaccctgaa 720

[2004] aacattttcc tgccggcggc ccgcatgctg tctgatctgg gcatcgcttt tctgggtctg 780

[2005] cgtgaaggta ccccggaagg cacttttggc cgtaccgatc agccaaagct gtccccgaaa 840

[2006] atccgtgagg ttttcaaccc accgctgatc ctcaaccaag actataacct ggaaaccgcg 900

[2007] caggaagctc tggacagcgg tgtcgccgat gcaatctctt tcggccgcct cttcatcagc 960

[2008] aacccggacc tgccgcgtcg cttctttgaa ggctccccgc tgatcaaaga taacatcgca 1020

[2009] acctggtata ctcagggcgc ggaaggttac actgattacc cgctgatcgg taacgagatt 1080

[2010] ccggcgtaa 1089

[2011] Sequence Listing (ID): 116

[2012] atgccttcgt tgtttgaccc tatccgtttt ggcgccttca cagccaagaa ccgcatctgg 60

[2013] atggcgccct tgactcgcgg tcgtgccacc cgcgatcatg tacccaccga aatcatggcg 120

[2014] GAATATTATG Cgcagcgcgc ccagcgcggGcctcatcatcagtGaggcaactGGcatctct 180

[2015] CAGGAAGGGT TGGGTTGGCC TTATGCCCCA GGAATCTGGT CTGATGCCCC AAGTTGAAGC 240

[2016] TGGCTTCCAA TCACCCAGGC GGTACACGAT GCCGGCGGTC TGATCTTTGC GCAATTATGG 300

[2017] CACATGGGCC GTATGgtacc TAGCAACGTC AGTGGTATGC AGCCTGTtGC ACCGAGCGCA 360

[2018] TCGCAGGCgc cGGGcctGGG CCAtAcGTAc GATGGCAAGA AACCAtACGA TGTcGCgcGC 420

[2019] GCACtCcgCT TAGAtGAAAT CCCGCgtCTG CTTGAtGAtT ATGAAAgGC CGCCCgtCAT 480

[2020] GCGCTTAAAG CGGGCTTCGA TGGTGTACAA ATTcATGCgg CTAACGGCTA CCttATTGAT 540

[2021] GAATTCATTC GCGATTCGAC CAACCACGCc ATGACGAAT ATGGTGGAGC GGTcGAAAgC 600

[2022] CGCATCCGCC TGCTGAAAGA TGTCAccGAA CGTGTtATCG CAACCAtCGG TAAGGAACGC 660

[2023] ACTGCGGTCC GTCTGTCGCC TAACGGAGAA ATTcAGGGCA CTGTTGATAG CCATCCGGAA 720

[2024] caggtgttta ttccggcagc gaaaatgttg agcgatctgg acatcgcatt cttaggaatg 780

[2025] cgcgagggcg ctgtagacgg tactttcggt aagaccgatc agccaaaatt gtctccggag 840

[2026] attcgcaaag tgtttaagcc ccctctcgtg ctgaatcagg actatacatt cgagaccgca 900

[2027] caggcggcgc tggattccgg cgttgccgac gcgatttcgt tcggccgtcc ttttatcggc 960

[2028] aacccggatt tgccacgccg tttcttcgaa aaggccccac ttactaaaga tgttattgaa 1020

[2029] acctggtaca cacaaacccc gaaaggatat acggattacc ctctgttagg cgactga 1077

[2030] SEQUENCE ID (ID): 117

[2031] atgaccagcc tgtttgagcc gatcgaactg ggttccatct acgcaaaaaa ccgtatcctg 60

[2032] atggcaccac tgacccgtgg ccgttctact cgcgaccacg tgccgactcc tattatggcg 120

[2033] gaatattacg ctcagcgtgc tggtgctggc ctgattatct ccgaagctac cggcatcagc 180

[2034] cgtgaaggcc tgggctggcc gtatgctcca ggtctgtggt cccaggagca ggttgaagcc 240

[2035] TGGAAGCCGA TCACCgcGGC AGTACACGCG AAAGGCGGTA AAATCGTTGC ACAGCTGTGG 300

[2036] CACATGGGCC GTATGGTTCA TTCTAGCGTA ACCGGTCAAC AGCCGGTATC CTGCTCTGCG 360

[2037] ACCAAGCGCC GGAAGCGCTG CACACCTATG ACGGCAAAC A GGCACCggA AGTGGCTCGT 420

[2038] CCGCTCACGA AAGAAGATAT CGCCCGATC CTGAACGATT ACGAAAACGC CgcACGTAAC 480

[2039] GCCCTGCAGG CGGTTTTGAC GGCgtACAG ATTCACGCTG CCAATGgtTA CCTGATTGAC 540

[2040] GAATTCCTGC GCGACGGTAC CAATCACCGT TCTGACGAgt ACggCGGTTc TCCGGAGAAC 600

[2041] CgcATTcGCT TCCTGCgcGA AGTGACCgAA CgtGTTATcG CGACCATCGG TGCTCATAAA 660

[2042] ACGTCCGTTC GTCTGTCTCC GAACGGTGAC ACTCAAGGCT GcatCGACTC TcatCCGGAa 720

[2043] CAGGTGTTcg TTCCGGCATC TAAACTCCTG AACGACCTGG ACATTGCATT TCTGGAACtg 780

[2044] CgtGAACcGG GTCCGAACGG CACCTTTGGC AAAACCgATC AGCCAAAGCT GCACGGCCCA 840

[2045] attcgtgaag tgttccgtaa accgctggtg ctgaaccagg actacactcg cgaagaggca 900

[2046] atcgaaactg tcgcaaccgg cgtggccgac gctattagct ttggccgccc gttcctggcc 960

[2047] aacccggatc tggtgcgtcg cctggaagat aacctgccgc agaacaaaga cgatattcgt 1020

[2048] acctggtaca gccagggtgc cgaaggttac accgattatc cactggctcg ttaa 1074

[2049] SEQ ID (ID): 118

[2050] atgaccactc tgttcgatcc gatcaaactg ggcgcgattg cagccccaaa ccgtattatc 60

[2051] atggctccgc tgactcgcgg tcgctcttcc cgtggtcacg tgccgagcgc actgatggct 120

[2052] gaatattacg cccagcgcgc ctccgctggc ctgattatca cggaggccac cggtatcagc 180

[2053] caggaaggtc tgggctggcc gtacgcgccg ggcatctggt ctgatgaaca ggttgaagca 240

[2054] tggaagccga ttgttcgtgc tgttcacgat aaaggtggcc gtattgtgat gcaactgtgg 300

[2055] cacatgggcc gtatggtgca ctctaacgtg accggcctgc agccggtttc tgcctctcca 360

[2056] atggctccgc tgactcgcgg tcgctcttcc cgtggtcacg tgccgagcgc actgatggct 120acgactgctc cgggtgaggc gcatacttat gacggtaaga aaccatacga acaggcgcgt 420

[2057] gctctggaca tctctgaaat cccgcgcctc ctggcggact acgagaacgc cactcgtaac 480

[2058] gctctggctg caggcttcga cggtgttcaa atccacgcgg caaacggcta tctcatcgat 540

[2059] gaattcctgc gtgatagcac caacaaacgt actgatgctt acggcggtga accagaaaac 600

[2060] cgtatccgcc tcctgcgcga agtcaccgaa cgtgttatca gcgtggccgg tgcagatcgc 660

[2061] accgcagtcc gtctgtcccc gaacggtgag actcagggta ctattgattc taacccgatc 720

[2062] tctgtattcg taccggccgc aaaaatgctg tacgacctgg gtctggcctg gctggaactg 780

[2063] cgtgagccgg gccctaacgg cacgttcggc cgcactgatc agccgaaact gagcccgcag 840

[2064] attcgtcagg ttttcaaagc accgctggtg ctgaactccg actacactct ggaagaggcg 900

[2065] gaaaccgctg tgctggagga tcgtgcagac gctatctcct ttggtcgtaa attcctcgct 960

[2066] gaaaccgctg tgctggagga tcgtgcagac gctatctcct ttggtcgtaa attcctcgct 960aacccggacc tgccgcatcg ttttaagtct ggcctgccgc tgaaccgtga cgaaatgaag 1020

[2067] acttggtact ctcagggtcc gcagggctac gtggactacc cagcggcaag ctaa 1074

[2068] Sequence number (ID): 119

[2069] atgcctacat tatttgaccc aatcgatttt ggccccattc atgcgaagaa ccgcatcgta 60

[2070] atgtctcccc tgacccgtgg acgcgctgat aaagaggccg tccctactcc tatcatggcc 120

[2071] gaatattatg cccagcgcgc aagcgcaggc ctcatcatca ctgaagcaac gggaatcagt 180

[2072] cgcgagggcc tcggttggcc atttgcaccg ggcatctggt cagatgccca ggttgaggcg 240

[2073] tggaaaccga ttgtcgcagg ggtacatgcc aaaggtggca agatcgtatg ccagctgtgg 300

[2074] cacatgggac gcatggtaca ttctagcgtt accggcacgc agcctgtgtc gtcaagcgcg 360

[2075] acaaccgctc cgggtgaagt gcatacctat gaaggtaaga agccatttga gcaggcgcgt 420

[2076] gcaatcgatg cggccgatat ctcccgtatt ctgaacgatt acgaaaatgc ggcacgcaac 480

[2077] gccattcgtg ctgggtttga tggtgtgcag attcatgcgg cgaacggcta tctgatcgac 540

[2078] gaattccttc gtaacggaac caatcaccgc actgacgaat atggcggagt tcccgaaaat 600

[2079] cgtatccgtt tcctcaaaga ggtcaccgag cgtgtcatcg cagcaatcgg tgccgatcgt 660

[2080] actggagtgc gtctttctcc taatggcgat acacaggggt gcatcgatag cgcgcccgag 720

[2081] actgtgtttg ttccggccgc gaaactgctt caggatctcg gtgttgcgtg gttagaactt 780

[2082] cgtgaaccgg gtccaaacgg gacgttcgga aagacggatc aacccaagtt atcaccccag 840

[2083] attcgcaaag tctttctgcg ccctctcgtc ctgaatcaag attatacttt tgaagctgcg 900

[2084] cagaccgcct tggctgaagg taaagcggat gccattgcct tcggccgtaa gtttatcagt 960

[2085] aatccggatt tgccagaacg cttcgctcgt ggtatcgctt tgcaaccgga tgacatgaaa 1020

[2086] acatggtatt ctcaggggcc ggaaggatac actgattatc cctctgcgac aagtggtccg 1080

[2087] aactaa 1086

[2088] Sequence Listing (ID): 120

[2089] atgccgtccc tgtttgattc tatcgatctg ggcgcggtcc acgccgcaaa ccgcatcatt 60

[2090] atgtctccgc tgacgcgtgc tcgcgccacc gaaggtgctg tgccgacccc gctcatggtt 120

[2091] gaatattacg cccagcgcgc gggcgctggt ctgatcattt ctgaggccac cggtatctcc 180

[2092] cgtgaaggcc tcggttggcc gtgggctccg ggcatctgga gcgcggaaca ggtagcagcg 240

[2093] tggaaaccga tcactaaagc tgtccacgaa cgtggcggta agatcgtgtg ccaactgtgg 300

[2094] cacatgggtc gtatggtaca tagctctgtc accggtctgc aacctgtgtc cgcgtccccg 360

[2095] accacggcac cgggccagtc ccacacctac gaaggtaaga aaccatacga ggaagcacgt 420

[2096] gagctgcgtg tagatgagat cccacgcatc ctggcggact atgaaaacgc agcccgcaac 480

[2097] gctatcgagg ccggcttcga cggtgtacag attcacgccg ctaatggcta cctgattgac 540

[2098] gagttcctgc gcgacggtac taaccaccgt aaagatgaat atggcggtgc accggaaaat 600

[2099] cgtattcgcc tcctgcgtga ggttactgaa cgtgtagtgg cgactatcgg tgcagatcgt 660

[2100] acttctgtcc gtctgtcccc gaacggtgat actcagggca cggatgactc cgccccggaa 720

[2101] aaagtttttg taccggcagc taaagttctg caggatctgg gcgttgcctg gctggagctg 780

[2102] cgcgaaccag gcccagaagg caccttcggc aaaaccgatg aaccgaaact gagcccggaa 840

[2103] atccgcaagg ttttctctcg tccgctggtt ctgaaccagg actatactct ggaggatgcg 900

[2104] cagaaagcgg tgagctctgg cctcgccgac gcggtgtctt tcggccgtaa attcatcgcg 960

[2105] aacccagatc tgcctcgccg ttttgcggaa gagatcccgc tggccaaaga tgacatggcg 1020

[2106] acctggtact ctcaaggccc taagggttac accgattatc cgttcgcgga cgaataa 1077

[2107] SEQUENCE ID (ID): 121

[2108] atgccgaacc tgttcgaccc gctgcagctg ggtccgatca ccctgccgaa ccgcgttatc 60

[2109] atggcaccgc tgacccgcct gcgtggtacc ccggatcaca tcccgacccc gctgatcgct 120

[2110] GAATACTATG CCCAGCgtgc gtccgcaggt ctgatcattt ctgaaggtac ccggtttct 180

[2111] CCAATGGGTG TAGGTTATGC TCAAGTCCCg ggcatctggt ctgaacaaca gactgaacag 240

[2112] TGGAGCCACA TTACGACCgc agtacacgcg gccggcggtc gtattttcgc ccagatctgg 300

[2113] CACGTtggtc gcgtttctca cccgctgttc ctgaacggtc aacagccagt ggcaccgacc 360

[2114] GCACtggccc cggaaggttt cgtgtccctg gtccgtccgc aacgcccatt cgaaacccct 420

[2115] Cgtgctctgg atatcgctga aattcgttcc accatcgctg actacaaacg tggtgcgcag 480

[2116] AACgcgaaag cagcgggctt cgacggcgta gaactgcatg gcgcgaacgg ttacctgatc 540

[2117] GATCAGTTCC TGCAGTCCGG CACCAACCAC Cgtacggacg cctatggtgg cccggttgaa 600

[2118] AACCGCGCAC GTTTcatgct ggaggctgta gatgctgtta gcgaagtatg gggcgcagac 660

[2119] CGCgtcggta tgcatctggc gccgcgtggt ggctatatga gcatctccga cgctaacccg 720

[2120] agcgaaacct tcggctatgt cgcgactgaa ctgggtaaac gtggtctggc gttcctgatg 780

[2121] tctcgcgaac atgagggtcc tgactggctg accccacagc tgaaacaaca gttcggtggc 840

[2122] gtgtacattg ccaacgaagg tttcacttac gaatccgcga acgccgcagt agaacgtggt 900

[2123] gactgtgacg ctgttggctt cggtaaactg ttcatttcta atcctgacct gccggctcgt 960

[2124] ttcgctcgcc aggcagaact gaccgcacct attccggaaa ccttctactc tcactctcct 1020

[2125] gagggttaca ttgattatcc ggcgctggcc taa 1053

[2126] Sequence Listing (ID): 122

[2127] atgccgaccc tgttcgatcc gatccgtatc ggtgacctcg acctgccgaa tcgtgtcatt 60

[2128] atggctccgc tgacccgtag ccgcgctgtt ggcggtggcc gcgtaccgaa cgcgctgatg 120

[2129] gcagaatatt acgttcagcg tgccagcgct ggcctgatcc tgtccgaagc taccgcagtt 180

[2130] accccacaag gcgtgggtta cgcggacacc ccgggcatct ggtctgagga acaggttgcc 240

[2131] ggctggaaac acgtgactga cgcggtgcat gctgcaggcg gtcgcatctt tctgcagctg 300

[2132] tggcacgtcg gccgtatttc cgatccggtt ttcctggacg gtgaactccc ggttgcaccg 360

[2133] tctgcaatcg ctgcaggtgg ccatgttagc ctggttcgtc cgaaacgtgc attcgtgacc 420

[2134] ccgcgtgctc tggaaactga agagattcca ggtatcgtag ccgcgtatcg tcatggcgcg 480

[2135] gaaaacgcaa aagctgccgg tttcgatggc gttgaagttc acggtgcgaa cggctacctc 540

[2136] ctggaccagt tcctgcagga ctccaccaac cagcgtaacg acgcctacgg tggctccatt 600

[2137] gagaaccgtg ctcgtctgct cctggaggta actgacgctt gtatcgccgt ttggggtccg 660

[2138] gcacgcgtag gtgtacatct ggctccgcgt ggtgatgcgc actctatggg cgattctgat 720

[2139] ccagcggcca ccttcggtta tgtggcacgc gaactgggca aacgtggcat cgctttcatc 780

[2140] tgctcccgtg aagcgctggg cgacaaccgt ctgggtccgg aactgaaacg cgcgttcggc 840

[2141] ggtacctata ttgccaacga aaaaatgacc aaagctactg cggagcatgt tctgcaggca 900

[2142] ggtgaggccg atgcagtcgc gtttggtcag ctcttcatcg cgaacccgga cctccctcgc 960

[2143] cgtctgcagc tcgacgcacc gctgaacgcg ccgcagccag aaacctttta tcacccaggt 1020

[2144] gcggaaggtt acattgatta cccggcgctg gcataa 1056

[2145] Sequence Listing (ID): 123

[2146] atgccgaccc tcttcgacac cctgacgctg ggtgatctga ccctgaaaaa tcgtatcgtg 60

[2147] atggcaccgc tgacccgctg tcgtgcagac gaaggtcgtg ttccaaatgc gatgatggca 120

[2148] gaatactatg ctcagcgttc tagcgcgggt ctgatcctga gcgaggcaac tagcgtaacg 180

[2149] gcaatgggcg ttggctatcc ggacacgcca ggcatctggt ccgatgcaca ggtacagggc 240

[2150] tggaagctga tcactgatgc ggtgcacgag gctggctccc gcattttcct gcagctgtgg 300

[2151] cacgtgggtc gtatctccga cccgagctat ctgaatggcg cgcagccggt cgccccgtct 360

[2152] atgccgaccc tcttcgacac cctgacgctg ggtgatctga ccctgaaaaa tcgtatcgtg 60

[2148] gaatactatg ctcagcgttc tagcgcgggt ctgatcctga gcgaggcaac tagcgtaacg 180

[2149] gcaatgggcg ttggctatcc ggacacgcca ggcatctggt ccgatgcaca ggtacagggc 240

[2150] tggaagctga tcactgatgc ggtgcacgag gctggctccc gcattttcct gcagctgtgg 300

[2151] cacgtgggtc gtatctccga cccgagctat ctgaatggcg cgcagccggt cgccccgtct 360gctgtgcgtc cggcaggtca tatctccctg gtgcgtccgc tgaaggacta cgacgaaccg 420

[2153] cgtgccctca ccctggctga gatcaaagaa gtcgtgcaag catatcgcca gggcgctatc 480

[2154] aacgccaaag ccgcaggctt cgatggtgtg cacatccacg gtgcaaacgg ctacctcctg 540

[2155] gatcagttcc tgcaggactc cacgaacctg cgtgacgatg agtacggcgg tagcctggaa 600

[2156] aaccgtgcgc gtctgatgct ggaagtcacc gatgcgtgca ttgacgtgtg gggtaaagac 660

[2157] cgtgtggcaa tgcatctggc gccgcgcatg gatgcgcacg acatgggcga ttctaaccgc 720

[2158] actgctacct tcggttatgt ggcgacggaa ctcggcaagc gcggtatcgc gttcatctct 780

[2159] acccgtgaac acgcagcgga tgactctatc accccgctca tcaaacagct gtttggcggt 840

[2160] ccggtgatcg ctaatgagaa attctccaag gcggaagcga atcagtggct ggccgagggt 900

[2161] aaagctgatg cagttgcctt tggtattccg tttatcgcta acccagacct gccgaaacgt 960

[2162] ctggagctgg acgcgccgct gaatgaaccg cgcaaagaac tgttttacgg caaaggtccg 1020

[2163] ctgggttata ccgactatcc gactctggct taa 1053

[2164] SEQ ID (ID): 124

[2165] atggccacga ttttcgaccc aatcaaactg ggcgatatcg aacttaaaaa ccggattatt 60

[2166] atggctccac tgactcgttg ccgggcggat gcgggtcgtg tgccgaatgc gctgatggca 120

[2167] gaatattatg ttcaacgtgc gtcagccggt ctcatccttt ccgaggcgac gagtgttacc 180

[2168] ccaatgggcg tgggttaccc agatacaccg ggaatctggt cgaacgatca agtccgtgga 240

[2169] tggagcaatg ttaccaaagc cattcatggc gcaggcggca aaattttcct gcagctgtgg 300

[2170] catgtcggtc gtatttcgca tccaagttat ctcaacggcg agacgccggt cgcgccgagc 360

[2171] gctattcagc caaagggtca cgttagcctg gtgcgtccct tagcggatta tccgacgccg 420

[2172] cgggccttag aaaccgcgga aatcgcggat atcgtggaag cttatcgtgt gggggcagaa 480

[2173] aacgcaaaag ccgccggctt tgacggtgta gaaattcatg gagcgaatgg ctatcttttg 540

[2174] gaccaatttc tgcaatcgag cacgaaccag cggaccgata gctatggtgg ctccctggaa 600

[2175] aatcgtgccc gtctgttact ggaagttacg gacgcggcga ttgaggtgtg gggtgccggg 660

[2176] cgggtcggag tgcatctggc acctcgggcg gacagtcatg atatgggcga cgagaatcgc 720

[2177] ttggaaacat tcagctatgt ggcgcgtgaa ttaggcaaac gcggtatcgc gtttatttgc 780

[2178] tcgcgtgaga aagagggcga tgatagtatt ggcccgcaac tgaaacaggc atttgggggg 840

[2179] ccgtatattg ccaacgaacg tttcacgaaa gattcagcga acgcttggct ggcggaaggc 900

[2180] aaagcggatg cagttgcctt cggtgtcccg tttatcgcga atcctgattt accagcccgc 960

[2181] ttgaaggcgg acgcgccgct gaatgaagca caccctgaaa cgttctacgg taaaggtccg 1020

[2182] gtgggttaca tcgactatcc cgttctctga 1050

[2183] Sequence Listing (ID): 125

[2184] atggcgacca tttttgatcc gatcaaactg ggcgatctgg agctgtctaa ccgcattatc 60

[2185] atggccccgc tgacccgttg ccgtgctgat gaaggtcgtg ttccgaatgc gctgatggct 120

[2186] gaatattacg tgcagcgtgc gtccgccggc ctgattctgt ccgaagcaac tagcgttacc 180

[2187] ccgatgggcg ttggctatcc ggataccccg ggcatttggt ccaatgacca agtacgtggc 240

[2188] tggactaaca tcactaaagc tgtgcacgct gcaggcggta aaatcgtcct ccagctgtgg 300

[2189] catgtgggtc gtatttccca cccgctgtac ctgaatggtg aagccccggt agcgccgtcc 360

[2190] gcaattcagc cgaagggtca cgtaagcctg gtacgtccgc tggctgacta cccaactcca 420

[2191] cgtgctctgg aaaccgctga gatcgcagaa atcgtcgaag cgtaccgtac cggcgcggaa 480

[2192] aacgctaaag cggctggctt cgacggcgtt gaaattcatg gtgcgaacgg ttacctcctg 540

[2193] gaccagtttc tgcagagctc caccaaccag cgtaccgata actatggtgg ctctctggaa 600

[2194] aaccgtgcgc gtctgctcct ggaagttacc gacgcagcga ttgacgtttg gggcgcgggt 660

[2195] cgcgtaggcg tacatctggc accgcgtgca gattctcacg atatgggtga tgacaacctg 720

[2196] gctgaaacct ttacctacgt ggcccgtgaa ctgggtaaac gcggcattgc tttcatctgc 780

[2197] tctcgtgaga aagagggcgc tgatagcctg ggtccgcagc tgaaggaagc gttcggtggc 840

[2198] gcttacatcg cgaacgagcg tttcactaaa gactccgcca acgcctggct ggctgaaggt 900

[2199] aaagccgacg ctgtagcgtt tggcgtaccg ttcatcgcta atccggacct gccggctcgt 960

[2200] ctgaaagcag acgcaccgct gaatgaaccg cgtccggaac tgttctacgg taaaggtccg 1020

[2201] gtcggttata ttgactatcc gaccctgtaa 1050

[2202] Serial number (ID): 126

[2203] atgagctaca tgaacttcga tccgaaaccg ctgggcgaca ccaacatctt caaaccgatt 60

[2204] aaaatcggta ataacgaact gaagcaccgt gttgtgatgc ctgcgctgac ccgcatgcgt 120

[2205] gcgatcgcgc cgggtaacat tccgaacacg gaatgggcag aagagtacta tcgccagcgt 180

[2206] agccaatatc cgggcaccct gattatcact gaaggtactt tcccgagcgc gcagagcggc 240

[2207] ggttatccga acgtcccggg catctggtct aaagaacagc tggcagagtg gaaaaagatc 300

[2208] ttcaacgcaa tccacgaaaa caagtccttc gtttgggtac agctgtgggt gctgggtcgt 360

[2209] caggcatggc cggaggtgct gaaaagag ggcctgcgtt acgattccgc tactgatgac 420

[2210] ctgtacatgg gcgaagga aaaagaacgc gctctgaagg caaacaatcc gcagcacggt 480

[2211] atcaccaagg aggaaatcaa acaatatatc aaagagtatg ttgacgccgc taagaaagca 540

[2212] attgacgcag gtgctgatgg cgtgcagatc cactccgcga atggttacct cctgaaccag 600

[2213] ttcctggatc cgatctccaa caatcgtacg gacgaatacg gtggctctat tgaaaatcgc 660

[2214] gcccgtttta ccctggaggt tgtggacgct gttgtggacg cggttggcgc agagcgtacc 720

[2215] tctattcgtt tttctcctta tggtaccttt ggtaccatgt ctggcggtga aaacccgggt 780

[2216] atcgtcgcac aatacgctta tgtaatcggc gaactggaaa aacgtgcacg tgcaggtaag 840

[2217] cgtctggcgt tcatcgacct ggttgaacct cgtgtgaccg atccgtttct gccggaattc 900

[2218] gaaaaatggt ttaaagaagg tactaacgaa ttcatttatt ctatctggaa aggcccagtt 960

[2219] ctgcgtgtgg gtaactacgc gctggatccg gatcaggcga ccctggactc taagaaacct 1020

[2220] aacaccctga ttggctacgg tcgttctttt attgctaacc cggacctggt gtaccgcctg 1080

[2221] gagaagggcc tgccgctgaa caaatacgat cgtaacactt tctacacttt cactaaagaa 1140

[2222] ggctatactg attacccgtc ctacgaggaa tctgtggcca agggctacaa gaaagaggaa 1200

[2223] aaaaagtatt aa 1212

[2224] SEQUENCE ID (ID): 127

[2225] atgtcctttg tgcaagattt taagccgatc gcgcttgctg acaccaaatt attcaagcca 60

[2226] attaagatcg gaaataacga gttggcgcac cgcgttgtaa tgccaccttt gacgcgtatg 120

[2227] cgtgcgaccc atccaggaaa tgtacctaat aaggattggg cggtagagta ttatgaccaa 180

[2228] cgttccaagc gtccaggcac gctgatcatt acagagggcg cctttcctag cgcgcaaagc 240

[2229] ggtggttatg acaatgtgcc tggcatttgg agcccagcgc aattggaaca atggaagaag 300

[2230] atctttgcga agatccacga gaataagtca ttcgtttggg tccaactgtg ggttcttggc 360

[2231] cgccagagtt tcgcggatac acttgcccgc gacggcttgc gttacgactc tgcttcagac 420

[2232] ggcgtgtata tggacgaaga gcaacgtgag cgtgccgtga agtccaacaa tcctcagcac 480

[2233] ggtctgacaa aggcggaaat caaacaatac atctcagagt acgtggacgc ggccaagaag 540

[2234] agtattgaag ccggggctga tggcgtggaa attcacagtg cgaacggata cctgttgaac 600

[2235] caatttctgg atcctattag taataaacgt actgacgagt atggtgggag catcgagaat 660

[2236] GCGTCGGCGGTTTCGTTCTGGAAATTTGTGGATGCCGTTACAGAGGGCCATTGGTTGC GATAAA 720

[2237] GTTGGTATTCTGTCTGAGCCCTTATGGCACGTTTG GTACCATGTCGG GTGGTCGGAGCCG 780

[2238] CTTATCGTGGCACAATTCGC GTACGTGCTCGGC GAATTAGAAAAGCGGCGCAAGGCTGGT 840

[2239] AAGCGCTTAAGCTTCGTGCACCTGTGCGAGCCGCGTGTTCACAACCCGTTCTACACCGAG 900

[2240] GGTCAGGGCGAATACAGAAGGAACAAATGACTTCGCCTATTCA GTGTGGAAGGGGCCCA 960

[2241] ATCATTCGTGCCGGCAATTTGGCTCTCCATCCC GAGGTAGTCAAGAAGATGGTTGAGGAC 1020

[2242] GACC GC ACTCTGATCGGGTACGGACGCTTCTTTATTTC C AATCCGGACATTGT T G ACCGT 1080

[2243] GTCGAAAAGGGTTTACCCCTTAACAAGTACAACC GTGATACCTTCTACGC GATGACCGCC 1140

[2244] AATGGTTACCTTGACTACCCGACGTATGATGAGGCCGTCAAGCTTGGCTATAAGTGA 1197

[2245] SEQUENCE ID (ID): 128

[2246] ATGCCTTTCGT TAAGGGGTT CGAACCCATCTCTCTCCGTGACACGAATTTATTTGAACCC 60

[2247] atcaaaatcg gtaataccca actcgcgcat cgtgctgtga tgccgccgtt aacgcgcatg 120

[2248] cgtgcgacgc atccggggaa catcccgaac aaaggaatggg cagcggtcta ctatgggcag 180

[2249] cgtgcccaac gtcctgggac catgatcatc actgagggca ccttcatcag tccgcaagcc 240

[2250] ggtggctacg acaatgcgcc tgggatctgg tctgatgagc aagtggcaga atggaagaat 300

[2251] atctttctcg cgattcacga ttgccagagc ttcgcatggg tacagttgtg gagcctcggc 360

[2252] tgggcgtcat tcccagacgt cttagcgcgc gatggtcttc gctatgattg cgcctcagac 420

[2253] cgtgtatata tgaacgcaac tcttcaagaa aaggcgaagg acgccaacaa cttagagcac 480

[2254] tcactgacta aggacgatat taagcaatat attaaagact acatccatgc ggcaaagaat 540

[2255] tcaatcgccg ctggtgccga cggtgtggag attcacagcg caaacggcta tctgttaaat 600

[2256] cagtttctgg acccccatag caataacgc accgacgagt atggcggtac gattgagaat 660

[2257] cgcgcccgtt tcacccttga ggtagtggac gccctgattg agacgattgg acctgagcgt 720

[2258] gttggactcc gccttagccc ttatggtacc tttaactcaa tgagcggtgg cgctgagcct 780

[2259] ggtatcattg cgcaatactc gtacgtcttg ggcgagttgg agaaacgtgc taaggccgga 840

[2260] aagcgcttag cgtttgtcca tcttgttgag cctcgcgtca ctgatccgtc gctggtcgag 900

[2261] ggcgagggtg agtatagcga gggcactaac gacttcgcat atagtatctg gaaaggtccg 960

[2262] attatccgcg cgggtaatta tgcgctccat cccgaggtgg tacgcgagca ggttaaggac 1020

[2263] ccacgcaccc tcattggata cggccgtttc tttatttcaa acccggacct tgtttaccgt 1080

[2264] ttggaagagg gtctgcctct caataagtac gaccgcagta ccttttatac catgtcagcc 1140

[2265] gaaggataca ctgattatcc aacctatgaa gaagcagttg acctcggttg gaataagaat 1200

[2266] tga 1203

[2267] SEQUENCE ID (ID): 129

[2268] atgccattcg tgaaggactt taagccgcaa gctctgggcg atactaactt atttaagcct 60

[2269] attaagatcg gtaacaacga acttttacat cgcgccgtga tcccgccttt aacccgcatg 120

[2270] cgcgcgcaac accctggtaa catccctaac cgtgattggg ctgtggaata ttacgcccag 180

[2271] cgtgcgcaac gtcctggtac tttaatcatt acggaaggga cattccccag cccgcagagt 240

[2272] ggtggttacg ataacgcgcc cggcatttgg tcagaggagc aaatcaagga atggacgaag 300

[2273] atctttaaag cgatccacga gaacaaaagc ttcgcttggg tgcaactgtg ggttctcggt 360

[2274] tgggctgctt ttccagatac cctggcccgt gacggattac gctacgactc cgcctcagat 420

[2275] aacgtataca tgaacgcgga acaagaggag aaggcaaaga aggctaacaa cccacaacat 480

[2276] tctatcacga aggatgaaat caagcaatat gtaaaagagt acgtccaagc agccaagaat 540

[2277] agtatcgctg cgggagctga tggtgtagag atccattcgg ccaatggcta tctcctgaac 600

[2278] caattcttag acccacacag caataaccgc acagatgagt atggcggatc catcgaaaat 660

[2279] cgtgcacgct ttacccttga ggttgtggac gccgttgtgg acgccatcgg tcctgagaaa 720

[2280] gtcggcctgc gcttatcccc atacggcgtg tttaattcta tgtctggcgg agcggagact 780

[2281] ggcatcgttg cgcaatatgc gtacgtatta ggtgaattgg agcgccgcgc taaggcaggc 840

[2282] aagcgcttag cgtttgtaca cttagtggag cctcgtgtta ctaatccatt cttaacagag 900

[2283] ggtgagggcg agtacaatgg tggtagcaac aagttcgcct atagcatttg gaaagggcct 960

[2284] atcatccgtg ccggaaactt cgcattacac ccggaagtcg ttcgtgaaga agtcaaagac 1020

[2285] ccgcgtactc tgatcggata cggacgtttc ttcatcagta atccggatct tgtggatcgc 1080

[2286] ctggagaaag gcttaccctt gaacaagtat gaccgcgaca cgttctacaa gatgtccgcc 1140

[2287] gaagggtata tcgattatcc tacatacgag gaagcgttaa agcttggctg ggataagaac 1200

[2288] taa 1203

[2289] Sequence Listing (ID): 130

[2290] atgagctttg taaaggattt caagccacag gcgcttggtg acactaactt attcaagcca 60

[2291] atcaagatcg gtaataatga gctcctgcat cgcgctgtaa ttccaccttt aacgcgcatg 120

[2292] cgcgcattgc acccggggaa tattccgaat cgtgattggg cggttgaata ctatacccag 180

[2293] cgtgcgcagc gtcccggcac gatgattatt actgagggag cttttatttc tcctcaagcg 240

[2294] ggtgggtacg ataatgcgcc gggagtatgg agcgaggaac agatggtgga atggacgaaa 300

[2295] atcttcaacg cgatccatga aaagaagagt tttgtctggg ttcagttatg ggtactgggg 360

[2296] tgggctgcct ttcctgataa cttagcacgt gacggtttgc gttacgactc cgctagcgat 420

[2297] aatgtattta tggacgccga gcaagaagcc aaggcaaaga aggcgaacaa ccctcaacac 480

[2298] tcacttacta aagatgagat caagcagtac atcaaggagt acgtgcaggc cgccaagaat 540

[2299] agtatcgccg ccggcgctga cggggtagag attcacagcg cgaatggata ccttctcaac 600

[2300] caatttctgg acccgcattc gaacacgcgc accgacgagt acggcggtag catcgagaac 660

[2301] cgcgcgcgtt ttactttaga ggtggtagat gcattggttg aggccatcgg tcatgagaag 720

[2302] gtcggccttc gcctctcgcc gtacggggtt ttcaattcta tgtccggtgg cgccgagacc 780

[2303] ggcattgtgg cccaatatgc ctacgttgcg ggcgaattag agaagcgtgc gaaggcaggc 840

[2304] aagcgcttag cctttgttca cttagtggag cctcgcgtga ccaacccgtt tctgaccgag 900

[2305] ggtgagggcg agtacgaagg cgggagcaat gactttgtgt acagtatctg gaagggaccg 960

[2306] gtcattcgcg ctggtaattt tgcgcttcac cccgaggtag tacgcgaaga agtgaaggac 1020

[2307] aaacgtacac ttatcggtta tggccgtttc ttcatttcta atccggatct cgtggatcgc 1080

[2308] ttagagaagg gcttaccgtt aaacaagtac gaccgcgata ctttctacca aatgtctgca 1140

[2309] catgggtaca ttgactaccc aacgtacgaa gaggccttaa agctcggttg ggacaagaag 1200

[2310] taa 1203

[2311] Sequence Listing (ID): 131

[2312] atgaccgtag gcctcgaaca gtctaacctg ttcaaaccga tcaccatcgg caaaaacact 60

[2313] ctggaccagc gtgttgcttt cgctccgact acccgttttc gcgcggccga cgatcatacg 120

[2314] ccgagcgacc tgatgctcca atactattct gaccgtgcgc aggcaccggg ttccctcctg 180

[2315] attaccgaag ccacgtttat ttctccgcgt gctggcctgt atccgaacat tccgggtatc 240

[2316] tggaatgaaa aacatgtgca gggttggaag aaaatcacgg atgcggttca cgcaaaaggt 300

[2317] tcctacatgg cctgccaatt ctggttcctg ggtcgtgtcg gctctccgga gctcctgaaa 360

[2318] aagcacggtc tggatctgat ctccccgagc gcgctgtatg aatctgagga aagcaagaaa 420

[2319] gcggctgaag cggctggcaa cccggttcgt gcgctcactg aaaaagaaat caagggtatc 480

[2320] atttacgagg attacaaaaa cgccgcgatc aacgctatgg aggcaggctt cgactacgtg 540

[2321] gaaatccact ccgcccacgg ttatatgctg gatcagttcc tgcagccggc gaccaatcag 600

[2322] cgcaccgata actatggcgg ttctattgaa aaacgtgctc gtatcgtgct ggagatcatt 660

[2323] gacctcctga gcgacaccat cggcgctgag aagctggcaa tccgcctctc tccgtgggcc 720

[2324] aaatttcaag gtatgaaagc tgaacaggac accgtgcatc cgatcacgac cttctcttat 780

[2325] gtagttaacg aactgcagaa gcgcgcaaat aacggtaaac agctggctta cctgtctctg 840

[2326] gtcgaaccgc gtgtacaggg taacctggac gttaacacga gcgacattgt tggttccaac 900

[2327] gatttcatca agaaactgtg gaaaggtgct attctgcagt ctggtaacta tacttatgat 960

[2328] tctcctgaat tcaaactcct gaaggcagac gtaaacggcg acaaccgtac gatgattggc 1020

[2329] ttctctcgct atttcactag caacccggac ctgatcgacc gcctgaaaaa gggtctggag 1080

[2330] ctgaccccgt acgtccgttc cctgttttac gccaccaata actacggtta caacaccttc 1140

[2331] gcgaactacg gtaaagaact gcaattcgat ccgaagaaag aggaaaaacg ccgtccggtg 1200

[2332] tctctgattt aa 1212

[2333] SEQUENCE ID (ID): 132

[2334] atgagctccg tgaagatcag cccattaaaa gactccgagg cgtttcagag tattaaagtt 60

[2335] ggaaataata cgctgcaaac caagatcgtt tatccgccga ccacccgctt ccgtgccctc 120

[2336] gaagaccaca cgccgtccga cctgcagttg cagtattacg gcgaccgttc aacattcccg 180

[2337] gggactctct taattactga ggctactttc gtgagtccgc aggcttcggg ctatgaagga 240

[2338] gcagcaccgg ggatttggac ggacaagcac gcgaaggcct ggaaggtcat taccgacaag 300

[2339] gtccacgcca acggtagttt cgtatcgacc cagcttattt tcttgggtcg tgtggctgac 360

[2340] cccgcggtca tgaaaacccg tggcttaaac ccggtgtcag catccgccac ctatgagagc 420

[2341] gatgccgcga aagaggccgc cgaggcagtc ggcaatcctg ttcgtgcact gacaacccaa 480

[2342] gaggtgaagg atctggtgta cgagacgtac actaacgcag cacaaaaggc catggatgcg 540

[2343] ggctttgact acattgagct tcacgcggca catgggtacc ttttagatca atttctgcaa 600

[2344] ccgtgtacaa accaacgcac cgacgagtat ggtggtagca tcgaaaaccg tgcccgctta 660

[2345] attttggaac tgatcgatca tttgtctact attgtcggtg cggataaaat cggtattcgt 720

[2346] atctcaccgt gggcgacttt tcaaaacatg aaggcccata aagacacggt acatccttta 780

[2347] accacgtttt catatttagt tcatgaactt caacaacgtg ccgataaagg gcagggcatc 840

[2348] gcatacatct ccgtggttga gccacgcgtt tcagggaacg tggatgtatc ggaagaggat 900

[2349] caggcgggtg acaacgaatt tgtcagcaag atttggaaag gcgtgatctt gaaggccgga 960

[2350] aactactctt acgacgcgcc ggagttcaag accctgaaag aggacatcgc cgataagcgt 1020

[2351] accttagttg gattttcgcg ctattttacg tcaaacccga acttagtctg gaagctgcgt 1080

[2352] gatggaatcg acctggtgcc atacgatcgc aatacctttt attctgataa taactacggt 1140

[2353] tataacacat tcagtatgga ctccgaagag gtggataagg aactggagat caaacgtgta 1200

[2354] cctagcgcga tcgaggcgct ttaa 1224

[2355] Sequence Listing (ID): 133

[2356] MTKVLAVLYP DPVDGFPPKY VRDDIPKITH YPDGSTVPTP EGIDFKPGEL LGSVSGGLGL 60

[2357] KKYLESKGVE FVVTSDKEGP DSVFEKELPT ADVVISQPFW PAYLTADLID KAKKLKLAIT 120

[2358] AGIGSDHVDL NAANEHNITV AEVTYSNSVS VAEAEVMQLL ALVRNFIPAH DIVKAGGWNI 180

[2359] ADAVSRAYDL EGMTVGVIGA GRIGRAVLER LKPFGVKLVY NQRHQLPDEV ENELGLTYFP 240

[2360] DVHEMVKVVD AVVLAAPLHA QTYHLFNDEV LATMKRGAYI VNNSRGEEVD RDAIVRALNS 300

[2361] GQIGGYSGDV WYPQPAPKDH PWRTMPNEAM TPHMSGTTLS AQARYAAGAR EILEDFLEDK 360

[2362] PIRPEYLIAQ GGSLAGTGAK SYTVKKGEET PGSGEAEK 398

[2363] Sequence Listing (ID): 134

[2364] MAKVLCVLYD DPVDGYPKTY ARDDLPKIDH YPGGQILPTP KAIDFTPGQL LGSVSGELGL 60

[2365] REYLESNGHT LVVTSDKDGP DSVFERELVD ADVVISQPFW PAYLTPERIA KAKNLKLALT 120

[2366] AGIGSDHVDL QSAIDRNVTV AEVTYSNSIS VAEHVVMMIL SLVRNYLPSH EWARKGGWNI 180

[2367] ADCVSHAYDL EAMHVGTVGA GRIGLAVLRR LAPFDVHLHY TQRHRLPESV EKELNLTWHA 240

[2368] TREDMYPVCD VVTLNVPLHP ETEHMINDET LKLFKRGAYI VNTARGKLCD RDAVARALES 300

[2369] GRLAGYAGDV WFPQPAPKDH PWRTMPYNGM TPHISGTTLT AQARYAAGTR EILECFFEGR 360

[2370] PIRDEYLIVQ GGALAGTGAH SYSKGNATGG SEEAAKFKKA V 401

[2371] Sequence Listing (ID): 135

[2372] atgaccaaag tgttagcagt tctgtatcca gatccagtgg atggtttccc accaaaatat 60

[2373] gtgcgggacg acattccaaa gattacccac tatccagatg gctcgacggt tccgacacct 120

[2374] gaggggattg acttcaagcc gggtgagtta ttgggcagtg tgtctggtgg cttgggactg 180

[2375] aagaaatatt tggaatctaa aggtgttgaa tttgtggtca cttcagacaa ggaaggcccc 240

[2376] gattcagtat ttgaaaagga acttccaacc gctgacgttg tgatttccca accattctgg 300

[2377] ccagcctatc tgacagctga tttaattgat aaagccaaga aattaaaatt agcgatcact 360

[2378] gccgggattg gttcagatca cgttgatttg aacgctgcca atgagcacaa tattaccgtt 420

[2379] gccgaagtca cttatagcaa cagtgtcagt gtggctgaag ctgaagtcat gcagttattg 480

[2380] gcattagttc gaaacttcat tccggctcac gacattgtta aagctggcgg ctggaacatc 540

[2381] gctgacgccg tttcacgggc ctatgatttg gaaggcatga ccgtcggcgt gatcggtgct 600

[2382] ggtcgaattg gccgggccgt actggaacgg ttaaaaccat ttggggttaa attagtttac 660

[2383] aaccagcgtc atcaattacc tgatgaagtt gaaaatgagc tgggactgac ctatttccct 720

[2384] gacgttcatg aaatggtcaa agtcgttgac gccgttgtct tagctgcacc actgcacgct 780

[2385] cagacctacc acctgtttaa cgacgaggtg ctcgctacta tgaaacgtgg ggcttacatc 840

[2386] gttaacaaca gtcgtggtga agaagttgat cgagacgcga ttgtgcgggc cctgaattct 900

[2387] ggtcaaattg gcggctactc tggggatgtt tggtacccac agccggcacc aaaggatcac 960

[2388] ccttggcgga ccatgccgaa tgaagctatg accccacata tgtccggaac aactttatct 1020

[2389] gcccaggcac gatacgcagc cggcgctcgg gaaattctcg aagacttctt agaggacaaa 1080

[2390] ccgatccgtc ctgaatacct gattgcccaa ggcggtagtt tagctggaac gggtgctaag 1140

[2391] tcctacactg tcaagaaagg tgaggagaca cccggaagtg gggaagctga gaagtag 1197

[2392] Sequence Listing (ID): 136

[2393] atggctaaag ttctgtgcgt tctctacgat gacccggtgg acggctaccc taaaacctac 60

[2394] gcgcgcgatg acctgccgaa aatcgatcac tacccgggcg gtcagattct gccaacccct 120

[2395] aaagcgattg acttcactcc tggtcagctc ctgggctccg tgtctggtga actgggcctc 180

[2396] cgtgaatatc tggaatccaa cggtcatacc ctggtggtta ccagcgacaa ggacggtccg 240

[2397] gacagcgttt ttgagcgtga actcgttgac gcggacgtag tgatctctca gccattctgg 300

[2398] ccagcttacc tgaccccgga gcgcatcgcc aaagcaaaaa acctgaaact ggctctgacc 360

[2399] GCTGGCATCG GTTCCGACCA CGTTGACCTC CAGTCCGCAT CGACCgCAAC GtaaccGTG 420

[2400] GCCGAAGTTA CTTACTCTAA CAGCATTAGC GTAGCAGAAC ACgtggttat GATGATCCTG 480

[2401] AGCCTGgtGC GCAATTACCT CCCATCCCAC GAATGGGCgC GtaaaggcGG TTGGAACATC 540

[2402] GCAGATTGCG TCAGCCACGC GTATGATCTG GAAGCGATGC ACGTAGGTAC CgtggGCgcG 600

[2403] Ggtcgtatcg GCCTGGCTGT CCTGCgCCGT CTGGCACCgt TTGACGTACA CCTGCACtAC 660

[2404] ACCCAGCgtC ACCGCCTCCC GGAATCCGTT GAGAAGGAAC TCAACCTGAC GTGGCACgCA 720

[2405] ACCCGTGAAG ATATGTACCC Ggtttgtgat GTGgttACCC TGAACGTGCCT CTGCACcCT 780

[2406] GAAACCgAAC ACATGATCAA TGACGAAACC CTGAAACTGT TCAACGtGG CGCTTATATT 840

[2407] GTtaACACtG CTCGTGGTAa ACTGTGTgAC CgCGACGCgG TTGCTCgtGC CCTGGAAGC 900

[2408] GGCCGCCTCG CGGGCTACGC CGGCgATGTt TGgttCCCgC AGCCGGCTCC GAAAGACCAc 960

[2409] ccttggcgca cgatgcctta caacggcatg acccctcata tctctggtac taccctgacc 1020

[2410] gcacaagccc gttatgctgc gggcacccgt gaaatcctgg agtgtttttt cgaaggtcgt 1080

[2411] cctatccgcg atgaatacct gattgttcag ggtggcgcac tcgccggcac cggtgctcac 1140

[2412] tcctatagca aaggcaatgc aacgggtggc tctgaagagg ctgcaaaatt caagaaagca 1200

[2413] gtgtaa 1206

[2414] Sequence Listing (ID): 137

[2415] atgactaagg tgctggctgt tctgtacccg gacccggtgg atggcttccc accgaaatac 60

[2416] gttcgtgatg acatcccgaa aatcacccat tacccggatg gcagcaccgt gccgactccg 120

[2417] gagggtatcg atttcaagcc gggcgagctc ctgggttccg tatccggtgg cctgggtctg 180

[2418] aagaaatacc tggaatccaa aggtgttgaa ttcgtcgtaa cctctgacaa agaaggcccg 240

[2419] gactctgttt ttgaaaagga gctcccgacc gctgacgtgg taatctctca gccgttctgg 300

[2420] GCTGAAGTTA CTTATAGCAA CAGCGTTCGC GTTGCGGGAA GCAAGGTGTA GCAGCTCCT G 480

[2421] GCCGGTTATC GGCAGCGATC ACCTGGACCT GAACGCCGCA ACGAGCACA ATATCCTGTT 420

[2422] GCTGAAGTTA CTTATAGCAA CAGCGTTCGC GTTGCGGGAA GCAAGGTGTA GCAGCTCCT G 480

[2423] GCTCTGGTTC GCAATTTCAT CCCTGCACAC GACATCGTCA AAGCTGGTGG CTGGAACATC 540

[2424] GCAGATGCCT GTCTCGTGCC CTACGACCTG GAAGGCATGA CCGTAGGTGT AATCGGTGCT 600

[2425] GGCCGCGATC GGCAGCGGTT CTGGAACGCC TGAAACCGTT CGGTGTGAAC TGCTTATAC 660

[2426] AACCAGCGTC ATCAGCTGCC GGATGAGGTC GAAAACGAAC TGGGTCTGAC TTACTTCCCG 720

[2427] GATGTTCACG AAATGGTAAA GGCGTTGACG CGGTGGTTCT GGCCGCGCCG CTGCACGCC 780

[2428] CAAACCTACC ACCCTGTCAA CGACGAGGTG CTGGCGACCA TGAAACGCGG TGCCTACATC 840

[2429] GTCAATGACT CTCGTGGCGA GGAAGTTGAT CCGATGCCTC TCGTACGTGC GCTGAACGCT 900

[2430] ggccaaatcg gtggctactc tggtgacgtg tggtatccgc agccagctcc taaagaccat 960

[2431] ccttggcgta ctatgcctaa cgaggcgatg actccgcaca tgtccggtac cactctgtcc 1020

[2432] gctcaggctc gctatgctgc gggtgctcgc gaaatcctgg aagatttcct ggaggataaa 1080

[2433] ccaatccgcc cagagtatct gatcgcgcag ggcggttccc tggcgggtac tggcgcgaaa 1140

[2434] agctacaccg tgaagaaagg tgaggaaact ccgggtagcg gcgaagccga aaaataa 1197

[2435] Sequence Listing (ID): 138

[2436] atggctaaag tactgtgcgt gctgtacgat gacccggttg acggttaccc aaaaacctac 60

[2437] gcacgtgatg acctgccgaa aattgaccac tacccgggtg gccagatcct gccgaccccg 120

[2438] aaagcgatcg acttcacccc tggccagctc ctgggttctg tttctggtga gctgggcctg 180

[2439] cgtgaatatc tggagagcaa cggtcatacc ctggtcgtga cctctgataa agacggcccg 240

[2440] gattctgtgt tcgaacgtga gctggttgac gctgatgtcg tgatctccca accattttgg 300

[2441] ccggcgtatc tgacccctga gcgcattgca aaagccaaga acctcaaact ggcgctgacg 360

[2442] gcgggtattg gttctgacca cgtagacctg cagagcgcga tcgaccgtaa cgtgaccgtg 420

[2443] gcagaagtca cctactccaa cagcatttcc gttgccgaac acgtagttat gatgattctg

[2444] 540. agcctcgtgc gtaactacct gccttctcac gaatgggctc gtaaaggtgg ctggaacatc

[2445] gcagattgtg taagccacgc atacgacctg gaagcgatgc acgtaggtac cgttggcgcg 600

[2446] ggtcgcatcg gtctggcggt tctgcgccgt ctggcgcctt ttgacgttca cctgcactac 660

[2447] actcagcgtc accgcctccc ggaaagcgtg gaaaaagaac tgaacctcac ctggcatgct

[2448] acccgtgaag acatgtaccc ggtatgcgac gtggtaacc tgaatgttcc gctgcatccg 780

[2449] gaaaccgaac acatgattaa cgacgaacc ctgaagctct tcaaacgtgg cgcctacatc

[2450] gttaacactg cgcgtggcaa actgtgcgat cgtgatgccg tggcacgcgc actggaatcc

[2451] ggtcgtctgg caggctacgc gggcgatgtc tggttcccgc agcctgcacc gaaagaccac 960

[2452] ccttggcgca ctatgcctta caacggtatg accccgcaca tttctggtac taccctgacc 1020

[2453] gctcaagcac gttatgctgc aggcacccgc gaaatcctgg agtgtttctt tgaaggccgt 1080

[2454] ccgatccgtg acgaatatct gatcgttcag ggtggcgctc tggcaggtac cggtgcgcac 1140

[2455] agctactcta agggcaacgc gacgggcggt tctgaggaag ccgcgaaatt taagaaagcg 1200

[2456] gtataa 1206

Claims

1. A reduction method by hydrogenating the conjugated diene aldehyde of formula (I) to the deconjugated diene aldehyde of formula (II), The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R 2 and R 3 Each independently represents a hydrogen atom and a carbon atom. 1-3 Alkoxy, C 1-6 Alkyl or C 2-6 Alkenyl groups, each optionally substituted with a hydroxyl group or a C group. 1-3 alkoxy; or R 1 and R 2 Together they form C 3-8 cycloalkyl or C 5-8 Cycloalkenyl; R 4 R 5 and R 6 Each can independently represent a hydrogen atom, a methyl group, or an ethyl group; The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 To R 6 The meaning is the same as the definition in equation (I); The method is carried out in the presence of an oxidoreductase.

2. The method according to claim 1, wherein the oxidoreductase is an olefin reductase.

3. The method according to claim 2, wherein the olefin reductase has at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity with any one of the sequences in SEQ ID NO: 1 to 44.

4. The method according to any one of the preceding claims, wherein the reduction is carried out in the presence of a cofactor; preferably, the cofactor is selected from NADPH and NADP. + NADH and NAD + .

5. The method according to any one of the preceding claims, wherein the reduction is carried out in the presence of a cofactor regeneration system.

6. The method according to any one of the preceding claims, wherein the method is an in vivo or in vitro method.

7. The method according to any one of the preceding claims, wherein R 5 Methyl; R 4 and R 6 For hydrogen atoms, R 1 R 2 and R 3 Each can independently represent a hydrogen atom or a carbon atom. 1-3 alkyl.

8. The method according to any one of the preceding claims, wherein the compound of formula (I) conforms to the following formula: The compound is in the form of any one of its stereoisomers or mixtures thereof, and each R 1 and R 2 The meaning is the same as that defined in claim 1 or claim 7; Furthermore, the compound of formula (II) conforms to the following formula: The compound is in the form of any one of its stereoisomers or mixtures thereof, and each R 1 and R 2 The meaning is the same as that defined in claim 1 or claim 7.

9. A method for preparing a compound of formula (I), The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R 2 and R 3 Each independently represents a hydrogen atom and a carbon atom. 1-3 Alkoxy, C 1-6 Alkyl or C 2-6 Alkenyl groups, each optionally substituted with a hydroxyl group or a C group. 1-3 alkoxy; or R 1 and R 2 Together they form C 3-8 cycloalkyl or C 5-8 Cycloalkenyl; R 4 R 5 and R 6 Each can independently represent a hydrogen atom, a methyl group, or an ethyl group; Includes the following steps: a) Converting the compound of formula (III) into an acetal of formula (IV), The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R 2 R 3 R 4 and R 5 The meaning is the same as the definition in equation (I); The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R 2 R 3 R 4 and R 5 The meaning is the same as the definition in equation (I); R a and R b Each represents C independently 1-4 Alkyl, or R a and R b When put together, it represents C 2-5 Alkyl; b) The acetal obtained in step a) is reacted with acid and formula R 6 -CH=CH-OR c The compound is treated to obtain a compound of formula (V), wherein R 6 The meaning is the same as the definition in equation (I), R c Representing C 1-4 alkyl, The compound is in the form of any of its stereoisomers or mixtures thereof, wherein R 1 R 2 R 3 R 4 R 5 R 6 R a R b and R c The meaning is the same as the definition above; and c) Treat the compound of formula (V) with acid to obtain the compound of formula (I).

10. The method of claim 9, wherein R a and R b Each represents C independently 1-3 Alkyl, R c It is methyl or ethyl; preferably, R a and R b Each of them represents a methyl group independently.

11. The method according to any one of claims 9 to 10, wherein step a) in acid and from C 1-4 Trialkyl orthoformate, C 1-4 alcohols and C 2-5 The reaction is carried out in the presence of reagents selected from the group consisting of diols.

12. The method according to any one of claims 9 to 11, wherein the acid used in step b) is selected from the group consisting of boron trifluoride complex, anhydrous zinc chloride and p-toluenesulfonic acid.

13. The method according to any one of claims 9 to 12, wherein the acid used in step c) is selected from the group consisting of formic acid, acetic acid, aqueous acetic acid solution, propionic acid, aqueous sulfuric acid solution, sulfuric acid solution, and aqueous hydrochloric acid solution.

14. A compound of formula (IV), The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R 2 and R 3 Each independently represents a hydrogen atom and a carbon atom. 1-3 Alkoxy, C 1-6 Alkyl or C 2-6 Alkenyl groups, each optionally substituted with a hydroxyl group or a C group. 1-3 alkoxy; or R 1 and R 2 Together they form C 3-8 cycloalkyl or C 5-8 Cycloalkenyl; R 4 and R 5 Each is independently a hydrogen atom, a methyl group, or an ethyl group; R a and R b Each represents C independently 1-4 Alkyl, or R a and R b Together they represent C 2-5 Alkyl.

15. A compound of formula (V), The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R 1 R 2 and R 3 Each independently represents a hydrogen atom and a carbon atom. 1-3 Alkoxy, C 1-6 Alkyl or C 2-6 Alkenyl groups, each optionally substituted with a hydroxyl group or a C group. 1-3 alkoxy; or R 1 and R 2 Together they form C 3-8 cycloalkyl or C 5-8 Cycloalkenyl; R 4 R 5 and R 6 Each can independently represent a hydrogen atom, a methyl group, or an ethyl group; R a and R b Each represents C independently 1-4 Alkyl, or R a and R b When put together, it represents C 2-5 Alkyl; R c Representing C 1-4 alkyl.

Images