Valencene synthase and its application

Abstract

The present invention relates to the field of biotechnology, and in particular to valencene synthase and its application. The Pfam domain of terpene synthase PF01397 and PF03936 is used as the core domain of a new valencene synthase, a new valencene synthase with valencene synthase activity is obtained by screening, and a coding nucleic acid molecule is designed according to the amino acid sequence of the screened new enzyme, and then a recombinant plasmid vector and an expression system for expressing the new enzyme are prepared, which can be applied to the synthesis of different citrus flavors, overcome the time-consuming and labor-intensive process of extracting essential oils from plants, and promote the industrial application of citrus flavors.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, in particular to valencene synthase and applications thereof. Background Art

[0002] Valencene is a sesquiterpenoid compound, which has been reported in various plant essential oils (e.g., grape seed essential oil, citrus essential oil, etc.), has a special smell, and can be used in food or daily chemicals. However, the whole process from planting to refining of plant essential oils is very complicated, time-consuming and labor-intensive, and requires a large amount of plant peels, so its extraction cost is quite high and its value is also quite expensive. In addition, the valencene content in natural plant extracts is very low, and it is difficult to separate plant essential oils containing high concentrations of valencene using the separation method of natural products. Therefore, finding a more economical way to obtain essential oil substances with special smells with high valencene concentrations is an inevitable trend to achieve economic efficiency and sustainable development. Summary of the invention

[0003] The object of the present invention is to provide a valencene synthase, and the use of the enzyme in an expression system for preparing a composition with a special flavor containing valencene as a main component, thereby achieving the purpose of efficient and continuous production.

[0004] In order to achieve the above object, the present invention provides the following technical solutions:

[0005] In a first aspect, the present invention provides a valencene synthase comprising domains with Pfam numbers of PF01397 and PF03936 and having valencene synthase activity. The valencene synthase is derived from plants of multiple families, such as plants of Rutaceae or Ranunculaceae Juss. An expression system capable of expressing the valencene synthase can be used for the fermentation production of a special odor composition.

[0006] In a second aspect, the present invention provides the use of the valencene synthase described in any of the preceding embodiments in the preparation of a flavor composition.

[0007] In a third aspect, the present invention provides a nucleic acid molecule comprising a nucleotide sequence encoding the valencene synthase described in any one of the preceding embodiments or a nucleotide sequence complementary to its base.

[0008] In a fourth aspect, the present invention provides a recombinant expression vector comprising the nucleic acid molecule described in any one of the preceding embodiments, wherein the original vector of the recombinant expression vector is pZY900, pYR017 or pYR018.

[0009] In a fifth aspect, the present invention provides a transformant, wherein the host cell of the transformant is selected from a fungal expression system, and contains the nucleic acid molecule described in any one of the preceding embodiments or the recombinant expression vector described in the preceding embodiments. Preferably, the fungal expression system is a yeast expression system, and more preferably a cerevisiae expression system.

[0010] In a sixth aspect, the present invention provides a recombinant Saccharomyces cerevisiae, wherein the recombinant Saccharomyces cerevisiae contains the nucleic acid molecule described in any one of the preceding embodiments, or contains the recombinant expression vector described in the preceding embodiments; preferably, the original vector of the recombinant expression vector is pZY900, pYR017 or pYR018.

[0011] In a seventh aspect, the present invention provides a flavor composition comprising 10% to 99% valencene by mass; the valencene is synthesized by the valencene synthase described in any one of the preceding embodiments.

[0012] In an eighth aspect, the present invention provides a method for preparing the flavor composition described in any of the aforementioned embodiments, the preparation method comprising fermenting and culturing the transformant or recombinant Saccharomyces cerevisiae described in the aforementioned embodiments, and recovering the flavor composition from the fermentation product.

[0013] In a ninth aspect, the present invention provides the use of the flavor composition described in any one of the preceding embodiments, or the flavor composition obtained by the preparation method described in any one of the preceding embodiments, in the preparation of a flavor product.

[0014] In a tenth aspect, the present invention provides a fragrance product comprising the fragrance composition described in any one of the preceding embodiments, or comprising the fragrance composition prepared by the method described in any one of the preceding embodiments.

[0015] The inventors used the Pfam domain containing terpene synthases PF01397 and PF03936 as the core domain of valencene synthase, hoping to screen for new synthases, and ultimately screen for new enzymes with valencene synthase activity, and designed encoding nucleic acid molecules based on the amino acid sequence of the screened valencene enzymes, and then prepared recombinant plasmid vectors and expression systems for expressing valencene synthase, which have the potential to be applied to the synthesis of different citrus flavors, making up for the time-consuming and labor-intensive plant extraction and promoting the industrial application of citrus flavors.

[0016] The expression system can be fermented and cultured to achieve the expression and preparation of the flavor composition, thereby obtaining a flavor composition mainly containing valencene.

[0017] Furthermore, the present invention provides for the first time valencene synthases derived from Rutaceae and Ranunculaceae, which are fermented in conjunction with a yeast expression system to produce a composition with citrus aroma. The amino acid sequences of the two valencene synthases are shown in SEQ ID NO: 1 (ArVS derived from Actaea racemosa), SEQ ID NO: 2 (ArVS-V8 derived from Actaea racemosa) and SEQ ID NO: 3 (CmVS-V4 derived from Citrus maxima), respectively.

[0018] Furthermore, the use of microbial fermentation methods to replace the extraction of plant-derived fragrance products from natural plant materials can eliminate the impact of climate on the growth of natural plants, and the yield and quality can be more stable. At the same time, the demand for plant raw materials can be reduced, and more planting resources can be released for other energy crops. Therefore, the use of microbial fermentation methods provided by the present invention to prepare a composition with a special fragrance has application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0020] Figure 1 Schematic diagram for the construction of plasmid pArVS;

[0021] Figure 2 Schematic diagram for the construction of plasmid pArVS-V8;

[0022] Figure 3 Schematic diagram for the construction of plasmid pCmVS-V4;

[0023] Figure 4 Schematic diagram for the construction of plasmids pVvVS, pCsVS, pShVS and pSlVS, pPvVS, pCnVS, pEgVS, and pAoVS. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments.

[0025] (I) Definitions or terms

[0026] The following abbreviations are used for the relevant definitions or terms involved in the present invention. Unless otherwise defined, all scientific and technological terms used herein have the meanings commonly understood by those of ordinary skill in the art. The following terms are provided below.

[0027] 1. Protein family classification database (Pfam database)

[0028] The Pfam database is a commonly used protein family database, which was created based on the protein data included in the UniProt database and is currently updated to version 35.0 (November 2021, 19632 data). In this database, you can download the hmm model file, alignment sequence, species information, HMM logo and other data corresponding to a gene family. The hmm model file contains the characteristic information of the gene family sequence, which can be used with the hmmer software to identify gene family members. The relevant website link is: https: / / www.ebi.ac.uk / interpro / entry / pfam / .

[0029] 2. Pfam domain

[0030] "Pfam domain" refers to a region within a protein sequence identified as Pfam-A or Pfam-B, and the identification process or method is designed based on multiple sequence alignments and the presence of hidden Markov motifs ("The Pfam protein families database": RDFinn, J. Mistry, J. Tate, P. Coggill, A. Heger, JE Pollington, OL Gavin, P. Gunesekaran, G. Ceric, K. Forslund, L. Holm, ELSonnhammer, SR Eddy, A. Bateman Nucleic Acids Research (2010) Database Issue 38: D211-222.).

[0031] 3. NIST

[0032] The NIST mentioned in the present invention refers to the National Institute of Standards and Technology (NIST), which is directly under the U.S. Department of Commerce and is engaged in basic and applied research in physics, biology and engineering, as well as research in measurement technology and test methods. It provides standards, standard reference data and related services and enjoys a high reputation internationally. The present invention refers to the NIST compound name database in the identification of the components in the composition obtained by fermentation.

[0033] 4. Novel valencene synthase

[0034] The novel valencene synthase described in the present invention refers to a valencene synthase that has not been successfully isolated and purified before the present invention. This is because valencene is a terpene compound, and traditional terpene synthases are usually natural enzymes. Enzymes with terpene synthesis expressed in plant cells under natural conditions are usually adapted to plant cell expression systems and terpene synthesis systems. The valencene synthase provided by the present invention is a novel enzyme that can be successfully expressed in an expression system and can synthesize valencene.

[0035] 5. Homology

[0036] The "homology" mentioned in the present invention has a meaning recognized in the art, and the percentage of sequence identity between two nucleic acids or polypeptides or regions can be calculated using publicly available techniques. For example, the sequence identity can be measured along the entire length of a polynucleotide or polypeptide or along a region of the molecule. Currently, there are many methods for measuring the identity between two polynucleotides or polypeptides that can be routinely selected by those skilled in the art according to actual needs.

[0037] 6. Expression

[0038] Expression of the present invention refers to the process of producing polypeptides by transcription and translation of polynucleotides. The expression level of polypeptides can be evaluated by any method known in the art, including methods such as measuring the amount of polypeptides produced from host cells. Such methods may include but are not limited to polypeptides in ELISA quantitative cell lysates, Coomassie blue staining after gel electrophoresis, Lowry protein assay and Bradford protein assay.

[0039] 7. Host Cells

[0040] The host cell of the present invention is a cell for receiving, maintaining, replicating and amplifying the vector. The host cell can also be used to express the polypeptide encoded by the vector. When the host cell divides, the nucleic acid contained in the vector replicates, thereby amplifying the nucleic acid. The host cell can be a eukaryotic cell or a prokaryotic cell.

[0041] 8. Carrier

[0042] The vector of the present invention is a replicable nucleic acid, and when the vector is transformed into an appropriate host cell, one or more heterologous proteins can be expressed from the vector. About vectors include those vectors into which nucleic acids encoding polypeptides or fragments thereof can be introduced, usually by restriction digestion and connection. About vectors also include those vectors containing nucleic acids encoding polypeptides. Vectors are used to introduce nucleic acids encoding polypeptides into host cells, for amplification of nucleic acids or for expression / display of polypeptides encoded by nucleic acids. Vectors usually remain free, but can be designed to integrate genes or parts thereof into chromosomes of the genome. Also contemplated are vectors of artificial chromosomes, such as yeast artificial vectors and mammalian artificial chromosomes. The selection and use of such vectors are well known to those skilled in the art.

[0043] (II) Detailed technical solution

[0044] In a specific embodiment, in a first aspect, the present invention provides a valencene synthase comprising domains with Pfam numbers PF01397 and PF03936 and having valencene synthase activity.

[0045] Among them, PF01397 is the N-terminal conserved domain of terpene synthase, and PF03936 is the C-terminal metal ion binding domain of terpene synthase. Screening genes containing both PF01397 and PF03936 Pfam domains can obtain complete plant terpene synthase.

[0046] The Pfam database is a collection of protein families, each of which is represented in the form of multiple sequence alignments and hidden Markov models.

[0047] 1. Download the Pfam database information (http: / / ftp.ebi.ac.uk / pub / databases / Pfam / releases / Pfam35.0 / ).

[0048] 2. Use hmmpress software to create an index for the local database.

[0049] 3. Use hmmscan software (E<0.01) to align the input protein sequence with the HMM domain library and return the domains contained in each protein.

[0050] 4. Filter out the results containing both PF03936 and PF01397 domains.

[0051] In an alternative embodiment, the valencene synthase comprises (a) a complete protein or a functional protein fragment derived from a plant; or (b) a derived valencene synthase having at least 80% amino acid sequence homology with (a).

[0052] Taking into account the cyclical growth and yield characteristics of plants, developing microbial alternative production methods for plant essential oils or plant-derived fragrance products has greater economic value and social significance than developing microbial alternative production methods for fragrances from other sources.

[0053] In some preferred embodiments, the above derivatization process can be to replace the amino acid site with another amino acid of the same type (having similar chemical properties or functions). As an example, the amino acids can be divided into the following categories according to their side chain properties: (1) non-polar amino acids: Ala (A), Val (V), Leu (L), Ile (I), Pro (P), Phe (F), Trp (W), Met (M); (2) uncharged polar amino acids: Gly (G), Ser (S), Thr (T), Cys (C), Tyr (Y), Asn (N), Gln (Q); (3) acidic amino acids: Asp (D), Glu (E); (4) basic amino acids: Lys (K), Arg (R), His (H). Alternatively, amino acids can be classified based on common side chain properties: (1) hydrophobic amino acids: Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic amino acids: Cys, Ser, Thr, Asn, Gln; (3) acidic amino acids: Asp, Glu; (4) basic amino acids: His, Lys, Arg; (5) amino acids that affect chain orientation: Gly, Pro; (6) aromatic amino acids: Trp, Tyr, Phe. Conservative substitutions between amino acids in the above homologous property classifications have little or no effect on the function, activity or other biological properties of the polypeptide.

[0054] In an alternative embodiment, the plant is selected from a plant of the Rutaceae family or a plant of the Ranunculaceae Juss. family.

[0055] In an alternative embodiment, the plant is selected from a plant of the genus Cimicifuga or a plant of the genus Citrus L.

[0056] In an alternative embodiment, the Cimicifuga plant includes Actaea asiatica, preferably Actaea racemosa, and the Citrus plant includes Citrus maxima.

[0057] Hemp plants are widely distributed and have long been used as medicinal plants. In existing phytochemical research reports, the most widely studied ones include China's Actaea asiatica and Actaea racemosa, which is widely distributed in Europe and the United States.

[0058] In alternative embodiments, the valencene synthase catalyzes the synthesis of valencene in an expression system.

[0059] In an alternative embodiment, the expression system comprises a fungal expression system.

[0060] In an alternative embodiment, the fungal expression system comprises a yeast expression system.

[0061] In an alternative embodiment, the yeast expression system comprises a Saccharomyces cerevisiae expression system.

[0062] In alternative embodiments, the amino acid sequence of the valencene synthase comprises (a) or (b):

[0063] (a) any one of SEQ ID NOs: 1 to 3;

[0064] (b) a derivative valencene synthase having at least 83%, 85%, 87%, 89%, 91%, 93%, 95%, 97% or more amino acid sequence identity to (a).

[0065] In a second aspect, the present invention provides the use of the valencene synthase described in any of the preceding embodiments in the preparation of a flavor composition.

[0066] In a third aspect, the present invention provides a nucleic acid molecule comprising a nucleotide sequence encoding the valencene synthase described in any one of the preceding embodiments or a nucleotide sequence complementary to its base.

[0067] In an optional embodiment, the nucleic acid molecule comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence homology to any of the nucleotide sequences shown in SEQ ID No:4 to 6.

[0068] In a fourth aspect, the present invention provides a recombinant expression vector comprising the nucleic acid molecule described in any one of the preceding embodiments, wherein the original vector of the recombinant expression vector is pZY900, pYR017 or pYR018.

[0069] In a fifth aspect, the present invention provides a transformant, wherein the host cell of the transformant is selected from a fungal expression system, and contains the nucleic acid molecule described in any one of the preceding embodiments or the recombinant expression vector described in the preceding embodiments. Preferably, the fungal expression system is a yeast expression system, and more preferably a cerevisiae expression system.

[0070] In a sixth aspect, the present invention provides a recombinant Saccharomyces cerevisiae, wherein the recombinant Saccharomyces cerevisiae contains the nucleic acid molecule described in any one of the preceding embodiments, or contains the recombinant expression vector described in the preceding embodiments; preferably, the original vector of the recombinant expression vector is pZY900, pYR017 or pYR018.

[0071] In a seventh aspect, the present invention provides a flavor composition comprising 10% to 99% valencene by mass, including but not limited to 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 99%; the valencene is synthesized by the valencene synthase described in any of the preceding embodiments.

[0072] In an eighth aspect, the present invention provides a method for preparing the flavor composition described in any of the aforementioned embodiments, the preparation method comprising fermenting and culturing the transformant or recombinant brewer's yeast described in the aforementioned embodiments, and recovering the flavor composition from the fermentation product.

[0073] In an alternative embodiment, the method of recovering comprises extracting the fermentation product using an oil phase.

[0074] In an alternative embodiment, the oil phase comprises at least one of isopropyl myristate or n-dodecane.

[0075] In an optional embodiment, the recovery method is to add an oil phase during the fermentation process, collect the oil phase after the fermentation is completed, and separate and obtain the flavor composition enriched in the oil phase.

[0076] In an alternative embodiment, the method of collecting the oil phase comprises centrifugation.

[0077] In an alternative embodiment, the separation method comprises distillation.

[0078] In a ninth aspect, the present invention provides the use of the flavor composition described in any one of the preceding embodiments, or the flavor composition obtained by the preparation method described in any one of the preceding embodiments, in the preparation of a flavor product.

[0079] In a tenth aspect, the present invention provides a fragrance product comprising the fragrance composition described in any one of the preceding embodiments, or comprising the fragrance composition prepared by the method described in any one of the preceding embodiments.

[0080] In an alternative embodiment, the fragrance product comprises a personal care product, a fabric care product, a cleaning product, a deodorant, a home care product, a fabric product, an air care product, a fragrance delivery system, a cosmetic preparation, a disinfectant or a food.

[0081] In an optional embodiment, the personal care product includes: floral water, skin care products, hair care products, antiperspirants, feminine care products, baby care products, oral hygiene products or health care.

[0082] In an alternative embodiment, the skin care product comprises soap, liquid soap or shower gel.

[0083] In an alternative embodiment, the oral hygiene product comprises a dental hygiene product.

[0084] In an alternative embodiment, the cosmetic preparation comprises a perfume, a fragrance liquid or an essential oil.

[0085] In an alternative embodiment, the cleaning product comprises a detergent composition.

[0086] In alternative embodiments, the decontamination composition comprises a dishwashing detergent, a glass cleaner, a metal cleaner, a countertop cleaner, a floor cleaner, a carpet cleaner, a toilet cleaner, or a bleach additive.

[0087] Some embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. In the absence of conflict, the following embodiments and features in the embodiments can be combined with each other.

[0088] Example 1 Preparation and application of valencene synthase from Actaea racemosa

[0089] 1.1 Gene mining of valencene synthase in Actaea racemosa

[0090] Referring to the published protein sequence information of Actaea racemosa (https: / / ftp.cngb.org / pub / gigadb / pub / 10.5524 / 100001_101000 / 100627 / assemblies / CYVA-Cimicifuga_racemosa / ), we searched for protein sequences containing both the Pfam domains of terpene synthase PF01397 and PF03936, and a total of 13 potential terpene synthase protein sequences were obtained.

[0091] 1.2 Identification of citrus aroma synthases and genes in Actaea racemosa

[0092] 1.2.1 Construction of yeast expression vector

[0093] Primers were designed to construct the gene to be verified on the universal vector pZY900 (using the same method as patent CN202210473488.4).

[0094] The verification processes of ArVS and ArVS-V8 derived from Actaea racemosa are shown here. The amino acid sequences of ArVS and ArVS-V8 are as shown in SEQ ID NO:1 and SEQ ID NO:2 respectively:

[0095] MEVTRRSANYHPSVWGDKFLEYSSPDHLKNDSDHLKNDAVTEKKHEKLKEEVKKMLVETVQKPQQQLNLINEIQRLGLSFHFEPEIEAALRQISVTYHEYCCSTNVDDLHNVALCFRILREHGHKVSCDVFHKFMDSNGKLKGSFLNDAIGLLSLYEATHFRVHGEDLLEDVLSLTTSRLEYLKSQMKYPLEDEITRALKHPLHKELNRLGARYYISIYEKYDSHNKLLLEFAKLDFNRMQKMYQHELAELTRWWKDLDFTNKLPFARDRIVEGYFWILGMYFEPECKDVREFLNRVFALISVVDDTYDVYGTFEEVILFTHAIERWETSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADCPTYRLEFAIETVKALFRSYLEEARWSKERYIPTMEEYMTVALVSVGYKTILTNSFVGMGDTATREVFEWVFSSPLIVRASDLIARLGDDIGGHEEEQKKGDAATAVECYMKEHGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPMTYITRVVHFTRAIHVIYADSDDGYTRPEKKIKGYITSLLVDPIPM(SEQ ID NO:1).

[0096] (SEQ ID NO:2).

[0097] The genes ArVS and ArVS-V8 from Actaea racemosa were directly synthesized according to the codon optimization of Saccharomyces cerevisiae, and the nucleotide sequences are shown in SEQ ID NOs: 4 and 5, respectively.

[0098]

[0099]

[0100] Specific gene primer pairs ArVS-1F / R and ArVS-V8-1F / R were designed. The synthetic genes were used as templates and the ArVS and ArVS-V8 gene fragments were obtained by PCR amplification using GXL high-fidelity enzyme from Novozymes. After gel recovery using Tiangen Gel Recovery Kit, the homologous recombination kit from Yishen was used to connect the fragments to the yeast expression vector pZY900 cut with BsaI by homologous recombination. After sequencing confirmation, yeast expression vectors containing the ArVS and ArVS-V8 gene fragments were obtained and named pArVS and pArVS-V8. The plasmid maps are shown in the following table. Figure 1 and Figure 2 As shown, the lacZ gene in pZY900 was replaced by the genes ArVS and ArVS-V8, respectively.

[0101] The ArVS-1F / R primer sequences are shown in Table 1 below:

[0102] Table 1

[0103]

[0104] The ArVS-V8-1F / R primer sequences are shown in Table 1 below:

[0105] Table 2

[0106]

[0107] 1.2.2 Strain construction

[0108] Plasmids pArVS, pArVS-V8 and pZY900 were introduced into strain JCR27 by the lithium acetate method (Li Xiaowei. Engineering acetyl-CoA pathway to construct an efficient synthesis platform for Saccharomyces cerevisiae [D]. Wuhan University, 2015.2.3.14 LiAc transformation of Saccharomyces cerevisiae) (the construction of yeast strain JCR27 is shown in the literature Siemon, Thomas et al. "Semisynthesis of Plant-Derived Englerin A Enabled by Microbe Engineering of Guaia-6,10(14)-diene asBuilding Block." Journal of the American Chemical Society vol.142,6(2020):2760-2765.doi:10.1021 / jacs.9b12940), and the transformed strains were named JArVS, JArVS-V8 and S900.

[0109] 1.2.3 Strain fermentation and product identification

[0110] Strains JArVS, JArVS-V8 and S900 were inoculated into SC-Ura liquid medium (Li Xiaowei. Engineering acetyl-CoA pathway to construct an efficient synthesis platform for Saccharomyces cerevisiae [D]. Wuhan University, 2015, uracil-deficient medium), and cultured overnight at 30°C, 200 rpm in a shaking incubator; the next day, they were transferred to 45 ml of YPDHG liquid medium (20 g / L peptone, 10 g / L yeast powder, 10 g / L glucose, 10 g / L galactose) at a 1% inoculum volume, 5 ml of isopropyl myristate was added, and the culture was carried out at 30°C, 200 rpm in a shaking incubator for 72 hours, the oil layer was collected, diluted to an appropriate concentration with n-hexane, and the product was detected by GC-MS.

[0111] GCMS detection conditions are: Thermo Fisher Scientific equipped with AS 3000 autoinjector, TRACE GCμLTRA gas chromatograph with split / splitless injector, and TSQ QUANTμm XLS MS equipped with triple quadrupole detector. The chromatographic column is TR-5MS colμmn (30m×0.25mm×0.25μm). The carrier gas is high-purity helium with a flow rate of 1mL / min. Acetone is used as needle wash liquid. The injection volume is 1μL, and the split ratio is 50. The injection port temperature is 240℃, and the ion transfer tube temperature is 270℃. Detection procedure: the initial column temperature is 50℃, maintained for 1min; the temperature is increased to 280℃ at 15℃ / min; the temperature is increased to 300℃ at 20℃ / min and maintained for 2min.

[0112] The results showed that valencene was not detected in the oil phase corresponding to the blank control strain S900, while valencene was detected in the oil phases corresponding to the strains JArVS and JArVS-V8, with the production of valencene being 110 mg / L and 230 mg / L, respectively.

[0113] Example 2 Functional Identification of Valencene Synthase from Citrus maxima (Pomelo, pummelo)

[0114] 2.1 Mining genes for the synthesis of citrus aroma compounds in Citrus maxima (Pomelo, pummelo)

[0115] Referring to the published protein sequence information of Citrus maxima (http: / / citrus.hzau.edu.cn / data / Genome_info / HWB.v1.0 / HWB.v1.0.protein.fa), we searched for protein sequences containing both the Pfam domains of terpene synthase PF01397 and PF03936, and obtained a total of 91 potential terpene synthase protein sequences.

[0116] 2.2 Identification of citrus aroma synthases and genes in Citrus maxima (Pomelo, pummelo)

[0117] 2.2.1 Construction of yeast expression vector

[0118] Primers were designed to construct the gene to be verified on the universal vector pZY900 (see patent CN202210473488.4).

[0119] Here we show the verification process of CmVS-V4 from Citrus maxima (Pomelo, pummelo). The amino acid sequence of CmVS-V4 is:

[0120] MSSGETFRPTADFHPSLWRNHFLKGASDFKTVDHTATQERHEALKEEVRRMITDAEDKPVQKLRLIDEVQRLGVAYHFEKEIEDAIQKLCPNYIHSNSPDLHTVSLHFRLLRQQGIKISCDVFEKFKDDEGRFKSSLINDVQGMLSLYEAAYMAVRGEHILDEAIAFTTTHLKSLVAQDHVTPKLAEQINHALYRPLRKTLPRLEARYFMSMINSTSDHLYNKTLLNFAKLDFNILLELHKEELNELTKWWKELDFTTKLPYARDRLVELYFWDLGTYFEPQYAFGRKIMTQLNYILSIIDDTYDAYGTLEELSLFTEAVQRWNIEAVDTLPEYMKLIYRTLLDAFNEIEEDMAKQGRSHCVRYAKEANQKVIGAYFVQAKWFSEGYVPTIEEYMPIALTSCAYTFVITNSFLGMGDFATKEVFEWISDNPKVVKAASVICRLLDDMQGHEFEQKRGHVASAIECYTKQHGVSKEEAIKMFEEEVANAWKDINEELMMKPTVVARPLLGTILNLARAIDFIYKEDDGYTHSYLIKDQIASVLGDHVPF(SEQ ID NO:3).

[0121] The gene CmVS-V4 derived from Citrus maxima (Pomelo, pummelo) was directly synthesized by optimizing according to the codons of Saccharomyces cerevisiae, and the sequence is shown in SEQ ID NO:6:

[0122]

[0123] The specific gene primer pair CmVS-V4-1F / R was designed, and the synthesized gene was used as a template. The CmVS-V4 gene fragment was obtained by PCR amplification using the GXL high-fidelity enzyme of Novozymes. After gel recovery using the Tiangen Gel Recovery Kit, the homologous recombination kit of Yishen Company was used to connect to the yeast expression vector pZY900 after BsaI cutting by homologous recombination. After sequencing confirmation, the yeast expression vector containing CmVS-V4 was obtained and named pCmVS-V4. The schematic diagram of the construction of plasmid pCmVS-V4 is shown in the figure. Figure 3 As shown, the lacZ gene in pZY900 is replaced by the gene CmVS-V4. The primer sequence of CmVS-V4-1F / R is shown in Table 3 below.

[0124] Table 3

[0125]

[0126] 2.2.2 Strain construction

[0127] The plasmid pCmVS-V4 was introduced into strain JCR27 by the lithium acetate method, and the transformed strain was named JCmVS-V4.

[0128] 2.2.3 Strain fermentation and product identification

[0129] The strain JCmVS-V4 was fermented and the product extracted according to Example 1.2.3.

[0130] The results showed that the valencene production of strain JCmVS-V4 was 215 mg / L.

[0131] Comparative Example Expression of existing valencene synthase gene

[0132] 1.1 Construction of plasmids containing valencene synthase genes from Vitis vinifera (Grape), Citrus sinensis (Sweet orange) (Citrus aurantium var. sinensis), Solanum habrochaites (Wild tomato) (Lycopersicon hirsutum), Solanum lycopersicum (Tomato) (Lycopersicon esculentum), Switchgrass (Panicum virgatum L.), Callitropsis nootkatensis, Eryngium glaciale, and Alpinia oxyphylla Miq.

[0133] The valencene synthases from different sources used in this comparative example are the valencene synthases that have been widely studied in the art and are recognized to have higher yields.

[0134] Primers were designed to construct the codon-optimized valencene synthase encoding gene on the universal vector pZY900.

[0135] The primer sequences designed for each gene are shown in the following table. Using the above synthesized genes as templates, yeast expression vectors containing VvVS, CsVS, ShVS, SlVS, PvVS, CnVS, EgVS, and AoVS genes were constructed in the same manner as in 2.1 of Example 1, and were named pVvVS, pCsVS, pShVS and pSlVS, pPvVS, pCnVS, pEgVS, and pAoVS. The schematic diagram of the construction of plasmids pVvVS, pCsVS, pShVS, and pSlVS, pPvVS, pCnVS, pEgVS, and pAoVS is shown in Figure 4 , which replace the lacZ gene in pZY900 with genes VvVS, CsVS, ShVS, SlVS, PvVS, CnVS, EgVS, and AoVS, respectively.

[0136] Table 4

[0137]

[0138] The amino acid sequence of valencene synthase from Vitis vinifera (Grape) is:

[0139] MSTQVSASSLAQIPQPKNRPVANFHPNIWGDQFITYTPEDKVTRACKEEQIEDLKKEVKRKLTAAAVANPSQLLNFIDAVQRLGVAYHFEQEIEEALQHICNSFHDCNDMDGDLYNIALGFRLLRQQGYTISCDIFNKFTDERGRFKEALISDVRGMLGLYEAAHLRVHGEDILAKALAFTTTHLKAMVESLGYHLAEQVAHALNRPIRKGLERLEARWYISVYQDEAFHDKTLLELAKLDFNLVQSLHKEELSNLARWWKELDFATKLPFARDRLVEGYFWMHGVYFEPQYLRGRRILTKVIAMTSILDDIHDAYGTPEELKLFIEAIERWDINSINQLPEYMKLCYVALLDVYKEIEEEMEKEGNQYRVHYAKEVMKNQVRAYFAEAKWLHEEHVPAFEEYMRVALASSGYCLLATTSFVGMGEIATKEAFDWVTSDPKIMSSSNFITRLMDDIKSHKFEQKRGHVASAVECYMKQYGVSEEQVYSEFQKQIENAWLDINQECLKPTAVSMPLLARLLNLTRTMDVIYKEQDSYTHVGKVMRDNIASVFINAVI (SEQ ID NO:29).

[0140] The nucleotide sequence VvVS after codon optimization in Saccharomyces cerevisiae is as follows:

[0141]

[0142] The amino acid sequence of valencene synthase from sweet orange (Citrus aurantium var. sinensis) is:

[0143] (SEQ ID NO:31).

[0144] The nucleotide sequence CsVS after codon optimization of Saccharomyces cerevisiae is:

[0145]

[0146] The amino acid sequence of valencene synthase from wild tomato Solanum habrochaites (Wild tomato) (Lycopersicon hirsutum) is:

[0147] (SEQ ID NO:33).

[0148] The nucleotide sequence of Saccharomyces cerevisiae after codon optimization is:

[0149]

[0150] The amino acid sequence of valencene synthase from Solanum lycopersicum (Tomato) (Lycopersicon esculentum) is:

[0151] (SEQ ID NO:35).

[0152] The nucleotide sequence of Saccharomyces cerevisiae after codon optimization is:

[0153]

[0154] The amino acid sequence of valencene synthase from switchgrass (Panicum virgatum L.) is:

[0155] (SEQ ID NO:37).

[0156] The nucleotide sequence of Saccharomyces cerevisiae after codon optimization is:

[0157]

[0158] The amino acid sequence of valencene synthase from Callitropsis nootkatensis is:

[0159] (SEQ ID NO:39).

[0160] The nucleotide sequence of Saccharomyces cerevisiae after codon optimization is:

[0161]

[0162] The amino acid sequence of valencene synthase from Eryngium glaciale is:

[0163] (SEQ ID NO:41).

[0164] The nucleotide sequence of Saccharomyces cerevisiae after codon optimization is:

[0165]

[0166] Plasmid construction of valencene synthase gene from Alpinia oxyphylla Miq. The amino acid sequence of valencene synthase from Alpinia oxyphylla Miq. is:

[0167] (SEQ ID NO:43).

[0168] The nucleotide sequence of Saccharomyces cerevisiae after codon optimization is:

[0169]

[0170] 1.2 Construction and shake flask fermentation of strains containing valencene synthase genes from Vitis vinifera (Grape), Citrus sinensis (Sweet orange) (Citrus aurantium var. sinensis), Solanum habrochaites (Wild tomato) (Lycopersicon hirsutum), Solanum lycopersicum (Tomato) (Lycopersicon esculentum), Switchgrass (Panicum virgatum L.), Callitropsis nootkatensis, Eryngium glaciale, and Alpinia oxyphylla Miq.

[0171] Plasmids pVvVS, pCsVS, pShVS, pSlVS, pPvVS, pCnVS, pEgVS, and pAoVS were introduced into strain JCR27 by the lithium acetate method, and the transformed strains were named JVvVS, JCsVS, JShVS, JSlVS, JPvVS, JCnVS, JEgVS, and JAoVS, respectively. The strains were fermented under the same shake flask fermentation conditions and methods as those in 1.2.3 and 1.3 of Example 1, and the shake flask fermentation yields of strains JVvVS, JCsVS, JShVS, JSlVS, JPvVS, JCnVS, JEgVS, and JAoVS were 0.35 mg / L, 15 mg / L, 0.06 mg / L, 0.07 mg / L, 1.5 mg / L, 40 mg / L, 80 mg / L, and 65 mg / L, respectively.

[0172] By comparing Examples 1 and 2 with the comparative example, it can be seen that the valencene synthase derived from Actaea racemosa and Citrus maxima (Pomelo, pummelo) provided by the present invention has higher synthesis activity than the existing valencene synthase.

[0173] Example 3 Construction of valencene high-yielding strain

[0174] 3.1 Recombinant plasmid construction

[0175] 3.1.1 Construction of high-yield plasmid corresponding to ArVS

[0176] Primers ZL-ArVS-1F / R and ZL-ArVS-2F / R were used to amplify the long fragment (including the left homology arm of Ura3, histidine selection marker, CYC1 terminator, tHMG1 gene, GAL1-GAL10 promoter, PGK1 terminator, right homology arm of Ura3, plasmid backbone) and ArVS using pYR017 (see patent 202210473488.4) and pArVS as templates, respectively. Subsequently, the above fragments were recombined in Saccharomyces cerevisiae to construct pArVS-P2 using the yeast assembly method.

[0177] The primer sequences of ZL-ArVS-1F / R and ZL-ArVS-2F / R are shown in the following table:

[0178]

[0179] Primers ZL-ArVS-1F / R and ZL-ArVS-2F / R were used to amplify the long fragment (including the left homology arm of yprcdelta15, tryptophan screening marker, GPM1 terminator, GAL1-GAL10 promoter, PGK1 terminator, right homology arm of yprcdelta15, plasmid backbone) and ArVS using pYR018 (see patent 202210473488.4) and pArVS as templates, respectively. Subsequently, the above fragments were recombined in Saccharomyces cerevisiae to construct pArVS-P3 using the yeast assembly method.

[0180] 3.1.2 Construction of high-yield plasmid corresponding to ArVS-V8

[0181] Primers ZL-ArVS-V8-1F / R and ZL-ArVS-V8-2F / R were used to amplify long fragments (including Ura3 left homology arm, histidine selection marker, CYC1 terminator, tHMG1 gene, GAL1-GAL10 promoter, PGK1 terminator, Ura3 right homology arm, plasmid backbone) and ArVS-V8 using pYR017 (see patent 202210473488.4) and pArVS-V8 as templates, respectively. Subsequently, the above fragments were recombined in Saccharomyces cerevisiae to construct pArVS-V8-P2 using the yeast assembly method.

[0182] The primer sequences of ZL-ArVS-V8-1F / R and ZL-ArVS-V8-2F / R are shown in the following table:

[0183]

[0184] Primers ZL-ArVS-V8-1F / R and ZL-ArVS-V8-2F / R were used to amplify long fragments (including yprcdelta15 left homology arm, tryptophan screening marker, GPM1 terminator, GAL1-GAL10 promoter, PGK1 terminator, yprcdelta15 right homology arm, plasmid backbone) and ArVS-V8 using pYR018 (see patent 202210473488.4) and pArVS-V8 as templates, respectively. Subsequently, the above fragments were recombined in Saccharomyces cerevisiae to construct pArVS-V8-P3 using the yeast assembly method.

[0185] 3.1.3 Construction of high-yield plasmid corresponding to CmVS-V4

[0186] Primers ZL-CmVS-V4-1F / R and ZL-CmVS-V4-2F / R were used to amplify long fragments (including Ura3 left homology arm, histidine selection marker, CYC1 terminator, tHMG1 gene, GAL1-GAL10 promoter, PGK1 terminator, Ura3 right homology arm, plasmid backbone) and CmVS-V4 using pYR017 (see patent 202210473488.4) and pCmVS-V4 as templates, respectively. Subsequently, the above fragments were recombined in Saccharomyces cerevisiae to construct pCmVS-V4-P2 using the yeast assembly method.

[0187] The primer sequences of ZL-ArVS-1F / R and ZL-ArVS-2F / R are shown in the following table:

[0188]

[0189] Primers ZL-CmVS-V4-1F / R and ZL-CmVS-V4-2F / R were used to amplify long fragments (including yprcdelta15 left homology arm, tryptophan screening marker, GPM1 terminator, GAL1-GAL10 promoter, PGK1 terminator, yprcdelta15 right homology arm, plasmid backbone) and CmVS-V4 using pYR018 (see patent 202210473488.4) and pCmVS-V4 as templates, respectively. Subsequently, the above fragments were recombined in Saccharomyces cerevisiae to construct pCmVS-V4-P3 using the yeast assembly method.

[0190] 3.1.4 Construction of gene editing plasmid

[0191] Primers GHX07-1F / R were used to amplify the obtained fragment using pKlURA100 (see patent 202210473488.4) as a template. The above fragments and pCas (see patent 202210473488.4) were then assembled using the Goldengate method to construct the plasmid pGHX07 targeting the ACH-TPS07 gene in strain LXF-5 (see patent 202210473488.4).

[0192] The primer sequences of GHX07-1F / R are shown in the following table:

[0193]

[0194] 3.2 Construction of high-yield strains

[0195] 3.2.1 Construction of high-yield strains corresponding to ArVS

[0196] Plasmids pArVS and pArVS-P2 were linearized using MssI, and plasmid pArVS-P3 was linearized using NotI, and the fragment containing ArVS was recovered from the gel.

[0197] The plasmid pGHX07 (transfer plasmid) and the linearized fragment of pArVS, the linearized fragment of pArVS-P2, and the linearized fragment of pArVS-P3 were jointly transferred into the strain LXF-5 by the lithium acetate method (see patent 202210473488.4), and the colony was verified by PCR to verify the correctness of the strain. Subsequently, YPD (tryptone, yeast extract, glucose) was used for culture and then washed with water. The bacteria were streaked on a 5-FOA plate, and the bacteria were picked from the plate to continue colony PCR to verify the correctness of the knockout. The correct strain was named JArVS-P1; the pZY521 knockout box (see patent 202210473488.4) was transferred into the strain JArVS-P1 to knock out the transcription repressor GAL80 to obtain the strain JArVS-P2.

[0198] 3.2.2 Construction of high-yield strain corresponding to ArVS-V8

[0199] Plasmids pArVS-V8 and pArVS-V8-P2 were linearized using MssI, and plasmid pArVS-V8-P3 was linearized using NotI, and the fragment containing ArVS-V8 was recovered from the gel.

[0200] The plasmid pGHX07 (transfer plasmid) and the linearized fragment of pArVS-V8, the linearized fragment of pArVS-V8-P2, and the linearized fragment of pArVS-V8-P3 were jointly transferred into the strain LXF-5 by the lithium acetate method (see patent 202210473488.4), and the colony was verified by PCR to verify the correctness of the strain. Subsequently, YPD (tryptone, yeast extract, glucose) was used for culture and then washed with water. The bacteria were streaked on a 5-FOA plate, and the bacteria were picked from the plate to continue colony PCR to verify the correctness of the knockout. The correct strain was named JArVS-V8-P1; the pZY521 knockout box (see patent 202210473488.4) was transferred into the strain JArVS-V8-P1 to knock out the transcriptional repressor GAL80 to obtain the strain JArVS-V8-P2.

[0201] 3.2.3 Construction of high-yield strain corresponding to CmVS-V4

[0202] Plasmids pCmVS-V4 and pCmVS-V4-P2 were linearized using MssI, and plasmid pCmVS-V4-P3 was linearized using NotI, and the fragment containing CmVS-V4 was recovered from the gel.

[0203] The plasmid pGHX07 (transfer plasmid) and the linearized fragment of pCmVS-V4, the linearized fragment of pCmVS-V4-P2, and the linearized fragment of pCmVS-V4-P3 were jointly transferred into the strain LXF-5 by the lithium acetate method (see patent 202210473488.4), and the colony was verified by PCR to verify the correctness of the strain. Subsequently, YPD (tryptone, yeast extract, glucose) was used for culture and then washed with water. The bacteria were streaked on a 5-FOA plate, and the bacteria were picked from the plate to continue colony PCR to verify the correctness of the knockout. The correct strain was named JCmVS-V4-P1; the pZY521 knockout box (see patent 202210473488.4) was transferred into the strain JCmVS-V4-P1 to knock out the transcription repressor GAL80 to obtain the strain JCmVS-V4-P2.

[0204] 3.3 Strain shake flask fermentation and fermentation tank evaluation

[0205] The strains JArVS-P1, JArVS-P2, JArVS-V8-P1, JArVS-V8-P2, JCmVS-V4-P1, and JCmVS-V4-P2 were inoculated into YPD liquid medium, respectively, and cultured overnight at 30°C, 200rpm; the next day, according to the initial OD600 = 0.1, they were transferred to 45 ml of YPDHG liquid medium (JArVS-P1, JArVS-V8-P1, JCmVS-V4-P1) or YPD liquid medium (JArVS-P2, JArVS-V8-P2, JCmVS-V4-P2), 5 ml of isopropyl myristate was added, and the culture was carried out at 30°C, 200rpm for 72 hours, and the oil layer was collected. Among them, the valencene production of JArVS-P1, JArVS-P2, JArVS-V8-P1, JArVS-V8-P2, JCmVS-V4-P1 and JCmVS-V4-P2 were 186 mg / L, 203 mg / L, 414 mg / L, 603 mg / L, 344 mg / L and 468 mg / L respectively.

[0206] Referring to the fermentation tank medium and fermentation method described in the literature (Ye Z, Huang Y, Shi B, et al. Coupling cell growth and biochemical pathway induction in Saccharomyces cerevisiae for production of (+)-valencene and its chemical conversion to (+)-nootkatone [published online ahead of print, 2022 Mar 13]. Metab Eng. 2022; 72: 107-115. doi: 10.1016 / j.ymben.2022.03.005), the constructed strains JArVS-P2, JArVS-V8-P2, and JCmVS-V4-P2 were subjected to batch fed fermentation, and a covering agent was added during the fermentation process to achieve in situ extraction, and the covering agent was isopropyl myristate. The fermentation process controlled the dissolved oxygen to be above 20%, the pH to be 5, the glucose concentration to be 1-2 g / L, and the ethanol concentration to be below 5 g / L. Finally, in a 1L fermentation tank, the strain's valencene production reached 6.1g / L, 17.5g / L and 13.1g / L respectively.

[0207] Example 4 Highly homologous amino acid sequence valencene synthase fermentation

[0208] Based on the amino acid sequences of ArVS and ArVS-V8 provided in Example 1 and CmVS-V4 provided in Example 2, amino acid sequences with homology of 80%, 83%, 85%, 87%, 89%, 91%, 93%, 95%, 97% and 99%, the corresponding nucleotide sequences optimized according to the codons of Saccharomyces cerevisiae, and the corresponding upstream and downstream primers were designed, and then the expression strains of valencene synthase with homologous amino acid sequences were constructed according to the method of Example 1, and fermented. The results showed that the valencene production obtained by the strains corresponding to ArVS, ArVS-V8 and CmVS-V4 with homology of 83% or more was equivalent to that of Example 1 and Example 2. The valencene production obtained by the strains corresponding to ArVS, ArVS-V8 and CmVS-V4 with homology of 80% decreased by more than 93% compared with the production of the corresponding strains with homology of 83%.

[0209] The different homologous amino acid sequences, nucleotide sequences and corresponding primers are shown in the following table:

[0210]

[0211]

[0212]

[0213] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

[0214] Part of the nucleotide and amino acid sequences are as follows:

[0215] (SEQ ID NO:55)

[0216] MEVKRRSANYKPSVWGDKFLEYSSPDALKADAKEAKKDAVTEKKLEKLSEEVAKKLVELVDKPQQALNLINEIERL

[0217] GLSHHFLPEIEAALRQISVTYDELCESLSVDDLDNVALCLRILRSHGHDVSAGVFEKFMDSNGKLKESFLNDAIGLLS

[0218] LYEATHYRVHGEDLLESLLSETTSLLEALKSQLKYPLKDLIELALKLPLYDLVNLLGARYYIKIYEKYSSHNKLLLEFA

[0219] KLSGNRMQKQYQHELAELVRDWKDLDTENKLPFARDNIVEGYFNILGMYAEPEHIDVREFLNRVFDLLSHIDDTYV

[0220] VYGTFEEVILFTNALERWEESALDQLPEDFKIIYQALMDVYSQEEEKLAKKEDAPKYRLEFAIETVKALTRSYLEIAR

[0221] WSKERYIPTVEEYMSVALVSCGASTILTCSFVGMGSEATREVFEWVSSSPLIVRASDLINALGRDIGSHEEEQKWGLA

[0222] ATYIECYMKEYGVTKQEAYAEAQKQIDNAKKDLNQEALRPFPVPREYITRVVNSTRTIRVIYADKHDGYTHPEKKIKGLIHSLLVQPIPM。

[0223] (SEQ ID NO:56)

[0224] ATGGAAGTCAAGCGTAGATCTGCTAACTACAAGCCATCTGTCTGGGGAGACAAATTCTTGGAATACTCCTCCCCA

[0225] GATGCCTTAAAGGCTGATGCCAAGGAAGCTAAGAAGGACGCTGTCACTGAAAAAAAGTTGGAAAAGTTGTCCG

[0226] AGGAAGTCGCGAAGAAGTTGGTTGAATTAGTTGACAAGCCACAACAAGCTTTGAATCTGATCAACGAAATTGA

[0227] AAGATTGGGTTTGTCTCATCACTTCCTACCAGAAATCGAAGCAGCTTTGAGACAAATCTCTGTTACCTACGACGA

[0228] GTTGTGCGAATCTTTGTCTGTCGATGATTTGGACAACGTTGCTTTGTGTTTGAGAATTTTGAGATCCCATGGTCAC

[0229] GACGTCTCCGCTGGTGTTTTCGAAAAGTTCATGGACTCTAACGGTAAGTTAAAAGAATCCTTCTTGAACGATGCT

[0230] ATTGGTTTGTTGTCCTTGTATGAAGCCACACATTACAGAGTTCACGGTGAAGACTTGTTAGAATCTTTGTTGTCTG

[0231] AAACTACTTCTTTGTTGGAAGCCTTGAAGTCTCAATTGAAATACCCATTGAAGGACTTGATTGAATTGGCTTTGA

[0232] AGTTGCCTCTGTACGATTTGGTTAACTTGTTGGGTGCGAGATACTACATCAAGATATACGAAAAGTACTCTTCACA

[0233] CAACAAGTTGTTGCTTGAGTTTGCCAAGCTGTCTGGTAACAGAATGCAAAAGCAATACCAACACGAATTGGCCG

[0234] AATTGGTCAGAGACTGGAAAGATTTGGATACCGAAAACAAGTTACCTTTCGCTCGTGATAACATTGTTGAAGGTT

[0235] ACTTCAACATCTTGGGTATGTACGCTGAACCAGAACACATTGACGTCCGTGAATTCTTAAACAGAGTTTTTGACT

[0236] TGCTGTCCCACATCGATGACACTTACGTTGTTTACGGTACTTTCGAAGAAGTTATTCTTGTTCACCAACGCTTTGGA

[0237] AAGATGGGAAGAATCCGCTTTGGACCAATTGCCAGAAGATTTCAAGATCATTTACCAAGCTTTGATGGATGTCTA

[0238] CTCACAAGAAGAAGAAAAGTTGGCTAAGAAGGAAGACGCTCCAAAGTACAGATTGGAATTCGCCATTGAAACT

[0239] GTTAAGGCTCTCACCCGTTCTTACTTGGAAATCGCCAGATGGTCTAAGGAAAGATACATCCCAACTGTCGAAGAA

[0240] TATATGAGTGTCGCCTTAGTGTCTTGTGGTGCTTCCACTATTTTGACTTGTTCTTTCGTTGGTATGGGTTCCGAAGC

[0241] TACCAGAGAAGTTTTTGAATGGGTTTCCTCCTCTCCACTTATCGTTAGAGCTTCTGACTTAATTAATGCTTAGGT

[0242] AGAGATATCGGTTCTCACGAAGAAGAACAAAAGTGGGGCTTAGCTGCTACTTATATCGAATGTTACATGAAGGAA

[0243] TACGGTGTCACCAAGCAAGAAGCTTACGCCGAAGCTCAAAAGCAAATTGACAACGCTAAGAAAGACTTGAACC

[0244] AAGAAGCTCTAAGACCATTCCCAGTTCCAAGAGAATATATTACCCGCGTTGTCAACTCCACCAGAACTATCAGAG

[0245] TAATCTACGCTGACAAGCACGATGGTTACACCCACCCAGAAAAGAAAATCAAGGGTTTGATTCACTCTTTATTGGTCCAACCAATTCCAATGTGA。

[0246] (SEQ ID NO:59)

[0247] MEVKRRSANYKPSVWGDKFLEYSSPDALKADAKEAKKDAVTEKKLEKLKEEVAKMLVETVDKPQQALNLINEIQR

[0248] LGLSHHFLPEIEAALRQISVTYDELCESLSVDDLDNVALCLRILRSHGHDVSAGVFEKFMDSNGKLKGSFLNDAIGLL

[0249] SLYEATHFRVHGEDLLESLLSLTTSLLEALKSQLKYPLKDEITLALKLPLYDEVNLLGARYYIKIYEKYSSHNKLLLEF

[0250] AKLDGNRMQKQYQHELAELVRDWKDLDTENKLPFARDRIVEGYFNILGMYAEPEHKDVREFLNRVFDLLSHIDDT

[0251] YVVYGTFEEVILFTNAIERWEESALDQLPEDMKIIYQALMDVYSQEEEKLAKKEDAPKYRLEFAIETVKALTRSYLEI

[0252] ARWSKERYIPTVEEYMSVALVSCGASTILTCSFVGMGDEATREVFEWVSSSPLIVRASDLINALGRDIGSHEEEQKWG

[0253] LAATYIECYMKEYGVTKQEAYAEAQKQIDNAKKDLNQEALRPFPVPREYITRVVNSTRTIRVIYADKHDGYTHPEKKIKGLIHSLLVQPIPM。

[0254] (SEQ ID NO:60)

[0255] ATGGAAGTTAAGAGAAGATCTGCTAACTACAAGCCTTCCGTCTGGGGTGACAAATTCTTGGAATACTCTTCTCCA

[0256] GATGCCTTGAAGGCTGACGCTAAGGAAGCTAAGAAGGATGCTGTCACTGAAAAGAAGTTAGAGAAGTTGAAGG

[0257] AAGAAGTCGCTAAGATGTTGGTTGAAACTGTTGACAAGCCACAACAAGCTTTGAACTTGATCAACGAAATCCAA

[0258] AGATTGGGTTTGTCCCATCACTTCTTGCCAGAAATTGAAGCTGCCTTGAGACAAATTCTCTGTAACTTACGATGAA

[0259] TTGTGTGAATCCTTGTCTGTCGATGATTTGGACAACGTTGCTCTATGTTTGAGAATTTTGAGATCCCATGGTCACG

[0260] ATGTTTCCGCTGGTGTCTTCGAAAAGTTCATGGACTCCAACGGTAAGTTGAAGGGTTCTTCTTGAACGATGCTA

[0261] TTGGTCTATTGTCCTTTGTACGAAGCTACCCATTTCAGGGTCCACGGTGAAGACTTATTGGAATCTTTGCTGTCTTT

[0262] GACCACTTCTTTGTTGGAAGCACTGAAGTCTCAATTGAAATACCCATTGAAGGACGAAATCACTTTGGCTTTGAA

[0263] GTTGCCATTGTACGACGAGGTTAATCTATTAGGTGCCAGATACTACATCAAGATCTACGAAAAGTACTCATCACAC

[0264] AACAAGTTGTTATTAGAATTTGCCAAATTGGATGGTAACAGAATGCAAAAGCAATACCAACACGAATTAGCTGAA

[0265] TTGGTCCGTGACTGGAAGGACTTGGACACTGAAAACAAATTACCATTTGCAAGAGACAGAATCGTCGAAGGTTA

[0266] CTTCAACATCTTGGGTATGTACGCTGAACCAGAACACAAGGACGTTAGAGAATTCTTGAACAGAGTTTTTGATCT

[0267] TTTGTCTCACATTGATGACACCTACGTTGTTTACGGTACCTTCGAAGAAGTCATCTTGTTCACCAACGCCATTGAA

[0268] AGATGGGAAGAATCTGCCCTCGACCAATTACCAGAAGACATGAAGATCATCTACCAAGCTTTGATGGATGTCTAC

[0269] TCCCAGGAAAGAAAAGTTGGCCAAGAAGGAAGATGCTCCAAAGTACAGATTGGAATTCGCTATCGAAACCG

[0270] TCAAGGCCCTAACAAGATCTTACTTGGAAATTGCTAGATGGTCTAAGGAACGTTACATTCCAACCGTTGAAGAAT

[0271] ATATGTCTGTTGCTTTAGTTTCTTGTGGTGCTTCCACTATTTTGACTTGCTCCTTCGTCGGTATGGGTGATGAAGCC

[0272] ACCCGTGAAGTTTTCGAATGGGTTTCTAGTTCCCCTTTGATTGTCAGAGCTTCTGACTTGATTAATGCTTTGGGTA

[0273] GAGATATCGGTTCCCACGAAAGAACAAAAGTGGGGATTGGCTGCTACTTACATAGAATGTTACATGAAAGAA

[0274] TATGGTGTTACCAAGCAAGAAGCTTACGCTGAAGCTCAAAAGCAAATTGATAACGCTAAGAAAGACTTGAACCA

[0275] AGAAGCCTTAAGACCATTCCCAGTTCCAAGAGAATACATTACCCGTGTTGTCAACTCTACCAGAACTATCAGAGT

[0276] GATCTATGCTGACAAGCACGACGGCTACACTCACCCAGAAAAGAAGATTAAGGGTTTGATTCACTCCTTACTCAACCAATCCCAATGTGA。

[0277] (SEQ ID NO:63)

[0278] MEVKRRSANYKPSVWGDKFLEYSSPDALKADSKEAKKDAVTEKKLEKLKEEVAKMLVETVQKPQQALNLINEIQR

[0279] LGLSFHFLPEIEAALRQISVTYDELCESLSVDDLDNVALCLRILRSHGHDVSAGVFEKFMDSNGKLKGSFLNDAIGLL

[0280] SLYEATHFRVHGEDLLESLLSLTTSLLEALKSQLKYPLKDEITLALKLPLYDEVNRLGARYYIKIYEKYSSHNKLLLEF

[0281] AKLDGNRMQKMYQHELAELTRDWKDLDTENKLPFARDRIVEGYFNILGMYAEPEHKDVREFLNRVFDLLSHIDDT

[0282] YVVYGTFEEVILFTNAIERWETSALDQLPEDMKIIYQALMDVYSQEEEKLAKKEDAPKYRLEFAIETVKALTRSYLEI

[0283] ARWSKERYIPTVEEYMSVALVSCGASTILTCSFVGMGDEATREVFEWVSSSPLIVRASDLINALGRDIGSHEEEQKWG

[0284] LAATYIECYMKEYGVTKQEAYAEAQKQIDNAKKDLNQEALRPFPVPREYITRVVNFTRAIRVIYADKHDGYTHPEKKIKGYITSLLVQPIPM。

[0285] (SEQ ID NO:64)

[0286] ATGGAAGTCAAGCGGAGATCTGCTAACTACAAGCCATCCGTCTGGGGTGACAAATTTTTGGAATATTCATCCCCA

[0287] GACGCCTTGAAAGCTGATTCCAAGGAAGCCAAGAAGGATGCTGTCACTGAAAAGAAATTAGAAAAATTAAAGG

[0288] AAGAAGTTGCCAAGATGTTGGTTGAAACTGTCCAAAAGCCACAACAAGCTTTAAACTTGATCAACGAAATCCA

[0289] AAGATTGGGTTTGTCTTTCCACTTTCTGCCAGAAATTGAAGCCGCTTTGAGACAAATCTCCGTTACTTACGACGA

[0290] ATTGTGTGAATCTTTGTCTGTCGATGACTTGGACAACGTTGCATTGTGCTTGAGAATCTTACGTTCTCACGGTCAC

[0291] GATGTTTCCGCTGGTGTATTCGAAAAGTTCATGGACTCTAACGGTAAGTTAAAGGGTTCTTTCTTGAACGATGCC

[0292] ATTGGTTTATTGTCATTGTACGAAGCTACTCACTTCAGAGTTCACGGTGAAGACCTTTTGGAAAGCCTCTTGTCTT

[0293] TGACCACTTCCCTATTGGAAGCTTTGAAGTCCCAATTGAAGTACCCATTGAAGGACGAAATCACCTTGGCCTTGA

[0294] AGTTGCCATTATATGATGAAGTCAACAGATTGGGTGCTAGATACTACATCAAGATCTACGAAAAGTACTCCTCTCA

[0295] CAACAAGCTGTTGTTGGAGTTTGCTAAGCTCGACGGAAACAGAATGCAAAAGATGTACCAACACGAATTAGCTG

[0296] AATTGACCAGAGATTGGAAAGACTTGGATACTGAAAACAAGCTACCTTTCGCTAGAGACAGAATTGTCGAAGGT

[0297] TACTTCAACATTTTGGGTATGTATGCTGAACCAGAACACAAGGACGTTCGTGAATTCTTGAATCGTGTCTTCGAC

[0298] TTGTTGTCTCACATTGACGACACTTACGTTGTTTACGGTACTTTCGAAGAAGTTATCTTGTTCACCAACGCTATCG

[0299] AAAGATGGAAACCAGTGCCTTGGACCAATTACCTGAAGACATGAAAATTATCTACCAAGCTTTGATGGACGTCT

[0300] ACTCTCAAGAAAGAAAAGTTGGCAAAGAAAAGAATGCTCCAAAGTACAGATTAGAATTCGCTATTGAAAC

[0301] CGTTAAGGCTTTAACTCGTTCCTACTTGGAAATCGCCAGATGGTCTAAGGAAAGATACATTCCAACCGTCGAAGA

[0302] ATATATGTCTGTCGCTTTGGTTTCTTGTGGTGCCTCCACTATCTTTGACCTGTTCCTTCGTTGGTATGGGTGATGAAG

[0303] CTACAAGAGAAGTTTTTGAGTGGGTTAGCTCTTCTCCATTGATTGTTAGAGCTTCTGATCTAATTAACGCTTTGGG

[0304] TAGAGACATTGGTTCCCATGAAGAAGAACAAAAGTGGGGTTTGGCTGCTACCTACATCGAATGTTACATGAAGG

[0305] AATACGGTGTCACAAGCAAGAAGCTTACGCTGAAGCTCAAAAGCAAATTGATAATGCTAAGAAGGATTTGAAC

[0306] CAAGAAGCCTTAAGACCATTCCCAGTTCCAAGAGAATACATTACTAGAGTTGTTAACTTCACCAGAGCCATCAGA

[0307] GTCATCTACGCTGACAAGCATGATGGTTACACCCATCCAGAAAAAAAGATTAAGGGTTACATCACTTCTTTATTGGTCCAACCAATCCCAATGTGA。

[0308] (SEQ ID NO:67)

[0309] MEVKRRSANYKPSVWGDKFLEYSSPDALKADSKEAKKDAVTEKKLEKLKEEVAKMLVETVQKPQQALNLINEIQR

[0310] LGLSFHFEPEIEAALRQISVTYDELCESLSVDDLDNVALCLRILRSHGHKVSAGVFEKFMDSNGKLKGSFLNDAIGLL

[0311] SLYEATHFRVHGEDLLESLLSLTTSRLEYLKSQLKYPLEDEITRALKLPLYDEVNRLGARYYIKIYEKYDSHNKLLLEF

[0312] AKLDGNRMQKMYQHELAELTRDWKDLDTENKLPFARDRIVEGYFNILGMYAEPEHKDVREFLNRVFDLISHVDDT

[0313] YVVYGTFEEVILFTNAIERWETSALDQLPEDMKIIYQALMDVYSQEEEKLAKKADAPKYRLEFAIETVKALTRSYLEI

[0314] ARWSKERYIPTVEEYMSVALVSCGASTILTCSFVGMGDEATREVFEWVSSSPLIVRASDLINALGRDIGSHEEEQKWG

[0315] LAATYVECYMKEYGVTKQEAYAEAQKQIDNAKKDLNQEALRPFPVPREYITRVVNFTRAIRVIYADKHDGYTHPEKKIKGYITSLLVQPIPM。

[0316] (SEQ ID NO:68)

[0317] ATGGAAGTCAAGAGAAGATCCGCTAACTACAAGCCATCTGTCTGGGGTGACAAATTCTTAGAATATTCCTCTCCA

[0318] GACGCTTTGAAGGCTGACTCCAAGGAAGCCAAAAAGGATGCCGTTACTGAAAAGAAATTGGAAAAGTTAAAGG

[0319] AAGAAGTTGCCAAGATGCTGGTCGAAACTGTTCAAAAGCCACAACAAGCATTAAACTTGATTAACGAAATCCAA

[0320] AGATTGGGTTTGTCCTTCCACTTCGAACCAGAAATTGAAGCTGCCTTGAGACAAATCTCTGTTACCTACGATGAA

[0321] TTGTGTGAATCATTGTCCGTTGACGATTTGGATAACGTTGCTCTATGCTTGAGAATCTTGAGATCTCACGGTCACA

[0322] AGGTTTCCGCTGGTGTTTTTGAAAAGTTCATGGATTCTAACGGTAAGTTGAAAGGTTCTTTCTTGAACGATGCTA

[0323] TTGGTTTGCTTTCCTTGTACGAAGCCACTCATTTCAGAGTTCACGGTGAAGATTTGTTGGAATCCTTGCTCTCTCT

[0324] CACTACTTCCAGATTGGAATATTTGAAGTCCCAATTGAAGTACCCCATTGGAAGACGAAATCACCAGAGCTCTAAA

[0325] GTTACCTTTATACGACGAAGTTAACCGTTTGGGCGCCAGATACTACATCAAGATTTACGAAAAGTATGACTCTCA

[0326] CAACAAGTTGTTGTTGGAATTCGCCAAATTGGATGGTAACAGAATGCAAAAGATGTACCAACACGAATTAGCTG

[0327] AATTAACCAGAGACTGGAAGGATTTGGACACCGAAAACAAGTTGCCATTTGCTAGAGACAGAATTGTTGAAGGT

[0328] TACTTCAACATCTTGGGTATGTACGCTGAACCAGAACACAAAGACGTTAGAGAATTTTAAATCGTGTCTTCGAT

[0329] CTAATATCTCACGTCGATGACACTTACGTCGTCTACGGTACTTTCGAAGAAGTCATTTTGTTCACCAACGCCATTG

[0330] AAAGATGGGAAACCTCCGCTTTGGACCAATTGCCAGAGGACATGAAAATCATCTACCAAGCTTTGATGGACGTT

[0331] TACTCTCAAGAAAGAAAAACTGGCTAAGAAGGCTGATGCCCCTAAGTACAGATTGGAATTCGCTATTGAAAC

[0332] TGTCAAGGCCTTGACCCGTTCTTACTGGAAATTGCTAGATGGTCCAAGGAAAGATACATTCCAACCGTTGAAGA

[0333] GTATATGTCTGTTGCTCTAGTCTCTTGTGGTGCTTCTACAATCTTGACTTGTTCTTTCGTTGGTATGGGTGATGAAG

[0334] CTACCCGTGAAGTCTTCGAATGGGTTTCTTCCAGTCCATTGATTGTCAGAGCTTCTGACTTGATCAATGCTTTAGG

[0335] TAGAGATATCGGTAGCCACGAAGAAGAACAAAAGTGGGGTTTGGCTGCCACTTACGTCGAATGTTACATGAAGG

[0336] AATACGGTGTCACCAAGCAAGAAGCTTACGCTGAAGCTCAAAAGCAAATTGACAACGCTAAGAAGGACTTGAA

[0337] CCAAGAAGCTTTAAGACCATTCCCAGTTCCAAGAGAATACATCACTCGTGTTGTCAACTTCACTAGAGCTATCAG

[0338] AGTTATCTACGCCGACAAGCATGACGGTTACACTCACCCAGAAAAGAAGATCAAGGGTTACATTACCTCTTTGTTGGTCCAACCAATCCCAATGTGA。

[0339] (SEQ ID NO:71)

[0340] MEVKRRSANYKPSVWGDKFLEYSSPDHLKNDSDELKKDAVTEKKLEKLKEEVAKMLVETVQKPQQALNLINEIQR

[0341] LGLSFHFEPEIEAALRQISVTYHELCESLNVDDLDNVALCLRILREHGHKVSAGVFEKFMDSNGKLKGSFLNDAIGLL

[0342] SLYEATHFRVHGEDLLESLLSLTTSRLEYLKSQLKYPLEDEITRALKLPLYKEVNRLGARYYIKIYEKYDSHNKLLLEF

[0343] AKLDGNRMQKMYQHELAELTRDWKDLDTENKLPFARDRIVEGYFNILGMYAEPECKDVREFLNRVFDLISHVDDT

[0344] YVVYGTFEEVILFTNAIERWETSALDQLPEDMKIIYQALMDVYSQEEEKLAKKADAPKYRLEFAIETVKALTRSYLEI

[0345] ARWSKERYIPTVEEYMSVALVSCGAKTILTCSFVGMGDEATREVFEWVSSSPLIVRASDLINALGDDIGSHEEEQKWG

[0346] LAATYVECYMKEYGVTKQEAYAEAQKQIDNAKKDLNQEALRPFPVPREYITRVVNFTRAIRVIYADKHDGYTHPEKKIKGYITSLLVQPIPM。

[0347] (SEQ ID NO:72)

[0348] ATGGAAGTCAAGAGAAGATCCGCTAACTACAAGCCATCTGTCTGGGGTGACAAATTCTTAGAATACTCCTCTCCA

[0349] GACCACTTGAAGAACGATTCCGATGAACTAAAGAAGGATGCTGTCACTGAAAAGAAATTGGAAAAGTTGAAGG

[0350] AAGAAGTTGCTAAGATGTTGGTCGAAACAGTCCAAGCCTCAACAAGCCTTGAACTTGATCAACGAAATCCA

[0351] AAGATTAGGTTTGTCTTTCCACTTTGAACCAGAAATTGAAGCAGCTTTGAGACAAATCTCCGTCACCTACCACGA

[0352] ATTGTGTGAATCCCTGAATGTCGATGATTTGGACAACGTTGCCTTGTGTTTGAGAATCTTGCGTGAACACGGTCA

[0353] CAAGGTTTCTGCTGGTGTCTTCGAAAAGTTCATGGACTCTAACGGTAAGTTGAAGGGTTCCTTCCTAAACGACG

[0354] CTATCGGTTTGTTGAGTTTGTACGAAGCCACTCACTTCAGAGTCCATGGTGAAGACTTGTTGGAATCTTTGTTGT

[0355] CCTTGACCACCTCAAGATTGGAATACTTGAAGTCTCAATTGAAATACCCATTGGAAGATGAAATCACTAGAGCTT

[0356] TAAAGTTACCTTTATACAAAGAAGTTAACCGTTTGGGAGCTAGATACTATATCAAGATTTACGAAGTACGATTC

[0357] TCACAACAAGTTGTTGTTGGAATTCGCTAAATTGGATGGTAACAGAATGCAAAAGATGTACCAACACGAATTAG

[0358] CTGAACTGACCAGAGACTGGAAGGACCTAGACACCGAAAACAAATTGCCATTTGCTCGTGACAGAATTGTTGA

[0359] AGGTTACTTCCAACATTCTGGGTATGTACGCTGAACCAGAATGTAAGGATGTTAGAGAATTCTTGAACAGAGTTTT

[0360] CGATTTGATTTCTCACGTTGACGACACTTACGTCGTCTACGGTACTTTCGAAGAAGTCATCTTGTTCACCAACGC

[0361] CATTGAAAGATGGGAAACTTCTGCTTTGGACCAATTGCCAGAAGACATGAAGATCATCTATCAAGCTTTGATGGA

[0362] TGTTTACTCTCAAGAAGAAGAGAAGTTGGCCAAGAAGGCTGATGCTCCAAAGTACAGACTAGAATTTGCCATTG

[0363] AAACTGTTAAAGCATTGACCAGATCTTACTTGGAAATTGCTAGATGGTCTAAGGAACGTTACATTCCAACTGTTG

[0364] AAGAATACATGTCCGTTGCTTTGGTTTCTTGTGGTGCTAAGACCATCTTGACTTGCTCCTTCGTTGGTATGGGTGTA

[0365] CGAAGCTACCCGCGAAGTTTCGAATGGGTTTCTTCTTCCCCATTGATTGTCAGAGCTTCTGACTTGATTAATGCT

[0366] TTGGGTGATGACATTGGTTCCCATGAAGAAGAACAAAAGTGGGGTTTAGCCGCTACTTACGTTGAATGTTACATG

[0367] AAAGAATACGGTGTTACCAAGCAAGAAGCTTACGCCGAAGCTCAAAAGCAAATTGACAATGCCAAGAAGGACT

[0368] TAAACCAAGAAGCTCTAAGACCATTCCCAGTTCCAAGAGAATATATCACTAGAGTCGTCAACTTCACTAGAGCCA

[0369] TTCGTGTTATCTATGCTGACAAGCACGATGGCTACACTCATCCAGAAAAGAAGATCAAGGGTTACATCACCTCTTTATTGGTTCAACCAATCCCAATGTGA。

[0370] (SEQ ID NO:75)

[0371] MEVKRRSANYKPSVWGDKFLEYSSPDHLKNDSDELKKDAVTEKKLEKLKEEVAKMLVETVQKPQQALNLINEIQR

[0372] LGLSFHFEPEIEAALRQISVTYHELCESLNVDDLDNVALCFRILREHGHKVSAGVFHKFMDSNGKLKGSFLNDAIGLL

[0373] SLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLYKEVNRLGARYYIKIYEKYDSHNKLLLE

[0374] FAKLDGNRMQKMYQHELAELTRDWKDLDTTNKLPFARDRIVEGYFNILGMYAEPECKDVREFLNRVFALISHVDDT

[0375] YDVYGTFEEVILFTNAIERWETSALDQLPEDMKIIYQALMDVYSQEEEKLAKKADAPTYRLEFAIETVKALTRSYLEI

[0376] ARWSKERYIPTVEEYMSVALVSCGAKTILTCSFVGMGDEATREVFEWVSSSPLIVRASDLINALGDDIGSHEEEQKWG

[0377] DAATYVECYMKEHGVTKQEAYAEAQKQIDNAKKDNLNQEALRPPFPVPRTYITRVVNFTRAIRVIYADKHDGYTHPEKKIKGYITSLLVQPIPM。

[0378] (SEQ ID NO:76)

[0379] ATGGAAGTGAAGAAGAATCTGCCAACTACAAGCCTTCTGTCTGGGGTGACAAATTCTTAGAATACTCTTCCCCC

[0380] AGACCACCTCAAGAACGACTCCGATGAATTGAAGAAGGACGCTGTTACTGAAAAAAAATTAGAAAAGTTGAAG

[0381] GAAGAAGTCGCTAAGATGTTGGTCGAAACCGTCCAAAAGCCACAACAAGCTTTGAACTTAATCAACGAAATCC

[0382] AAAGATTAGGTTTGTCTTTCCATTTCGAACCAGAAATTGAAGCTGCTTTGAGACAAATCTCTGTTTACTTACCATG

[0383] AATTGTGTGAATCCTTGAATGTCGATGATTTGGACAACGTTGCTTTATGTTTCAGAATCCTACGTGAACACGGAC

[0384] ACAAAGTTTCCGCTGGTGTCTTCCACAAGTTCATGGACTCAAACGGTAAGTTGAAGGGTTCTTTTTTGAACGAT

[0385] GCTATTGGTCTTTTGTCCTTGTATGAAGCCACCCACTTCAGAGTCCATGGTGAAGATTTGCTTGAAGACTTGTTAT

[0386] CATTGACCACCTCCAGATTGGAAATTTTGAAGTCTCAAATGAAGTACCCACTGGAAGATGAAATCACGAGAGCTT

[0387] TGAAGCATCCATTGTACAAGGAAGTCAACAGACTAGGTGCCAGATACTACATCAAGATTTACGAAAAGTACGATT

[0388] CCCACAACAAGTTGTTGTTGGAATTTGCTAAATTGGATGGTAACAGAATGCAAAAGATGTACCAACACGAACTG

[0389] GCCGAATTGACCCGTGACTGGAAGGATTTAGACACCACTAACAAGCTACCTTTTGCCAGAGACAGAATTGTTGA

[0390] AGGTTACTTCAACATTTTGGGTATGTATGCTGAACCAGAATGCAAAGATGTTAGAGAATTCTTGAACAGAGTTTT

[0391] CGCTTTGATATCTCACGTTGATGACACTTACGATGTTTACGGTACTTTCGAAGAAGTTATCTTGTTCACCAACGCC

[0392] ATCGAAAGATGGGAAACTTCTGCCTTGGACCAATTGCCAGAAGACATGAAGATTATCTACCAAGCTTTGATGGAT

[0393] GTCTACTCCCAAGAAGAGGAAAAGTTGGCTAAGAAGGCTGATGCTCCAACCTACCGTTTGGAATTCGCTATCGA

[0394] AACAGTCAAGGCTCTTACTAGGTCTTACTTGGAAATTGCTAGATGGTCTAAGGAACGTTACATTCCAACTGTTGA

[0395] AGAATACATGTCCGTTGCTTTGGTATCTTGTGGCGCCAAGACCATTTTGACTTGTTCTTTCGTTGGTATGGGTGAC

[0396] GAGGCTACCAGAGAAGTCTTTGAATGGGTTTCTTCCTCTCCATTGATTGTCAGAGCCTCTGACTTGATTAACGCT

[0397] TTGGGTGATGACATCGGTTCGCACGAAGAAGAACAAAAATGGGGTGACGCAGCTACTTACGTCGAATGTTACAT

[0398] GAAAGAACACGGTGTCACCAAGCAAGAAGCTTACGCTGAAGCTCAAAAGCAGATTGACAATGCTAAGAAGGAT

[0399] CTGAACCAAGAAGCCTTAAGACCATTCCCAGTTCCAAGAACCTATATTACTAGAGTTGTTAACTTCACTAGAGCT

[0400] ATCAGAGTCATTTACGCTGACAAGCACGACGGTTACACTCACCCAGAAAAGAAGATCAAGGGTTACATCACTTCCTTGTTGGTTCAACCAATCCCAATGTGA。

[0401] (SEQ ID NO:79)

[0402] MEVKRRSANYKPSVWGDKFLEYSSPDHLKNDSDELKKDAVTEKKLEKLKEEVAKMLVETVQKPQQALNLINEIQR

[0403] LGLSFHFEPEIEAALRQISVTYHELCESTNVDDLDNVALCFRILREHGHKVSADVFHKFMDSNGKLKGSFLNDAIGLL

[0404] SLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLYKELNRLGARYYISIYEKYDSHNKLLLEF

[0405] AKLDGNRMQKMYQHELAELTRDWKDLDTTNKLPFARDRIVEGYFNILGMYFEPECKDVREFLNRVFALISHVDDT

[0406] YDVYGTFEEVILFTHAIERWETSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADAPTYRLEFAIETVKALFRSYLEI

[0407] ARWSKERYIPTVEEYMSVALVSCGAKTILTCSFVGMGDTATREVFEWVSSSPLIVRASDLINALGDDIGSHEEEQKWG

[0408] DAATYVECYMKEHGVTKQEAYAEAQKQIDNAKKDLNQEALRPFPVPRTYITRVVNFTRAIRVIYADSHDGYTHPEKKIKGYITSLLVQPIPM。

[0409] (SEQ ID NO:80)

[0410] ATGGAAGTTAAGAGAAGATATCGCTAACTACAAGCCATCTGTCTGGGGTGACAAATTCTTGGAATACTCTTCTCCA

[0411] GACCACTTGAAGAACGACTCTGATGAATTGAAGAAGGATGCTGTCACTGAAAAGAAATTGGAAAAATTAAAGG

[0412] AAGAAGTTGCCAAGATGTTGGTTGAAACTGTTCAAGCCACAACAAGCCTTAAACTTGATCAACGAAATCCA

[0413] AAGACTAGGTTTGTCCTTCCATTTCGAACCTGAAATTGAAGCTGCCTTGAGACAAATTTCCGTTACTTACCACGA

[0414] ATTGTGTGAATCTACTAACGTCGACGATTTGGATAACGTCGCTCTCTGTTTCAGAATCTTACGTGAACATGGTCAC

[0415] AAGGTTTCCGCTGATGTCTTCCACAAGTTCATGGACTCTAACGGTAAGTTGAAGGGTTCTTTCTTGAACGATGCA

[0416] ATTGGCCTATTATCATTGTACGAAGCTACTCACTTCAGAGTCCACGGTGAAGATTTATTGGAAGACTTGTTGAGCT

[0417] TGACTACTTCTAGATTGGAATACTTGAAGTCTCAAATGAAGTATCCATTGGAAGACGAAATCACCAGAGCTCTTA

[0418] AGCACCCATTATACAAGGAATTGAACCGTTTAGGTGCTCGTTACTACATCTCGATCTACGAAAAGTACGATTCTCA

[0419] CAACAAGTTGTTGCTCGAATTCGCTAAGTTGGACGGTAACAGAATGCAAAAGATGTACCAACGAATTGGCTG

[0420] AATTAACTAGAGACTGGAAGGACTTGGATACCACCAACAAGTTGCCATTCGCTAGAGACAGAATTGTCGAAGGT

[0421] TACTTCAACATTTTGGGTATGTATTTTGAACCTGAATGTAAGGATGTTAGAGAGTTCTTGAATAGAGTTTTTGCCT

[0422] TGATTTCCCATGTCGACGACACTTACGACGTTTACGGTACTTTCGAGGAGGTCATCTTGTTCACCCACGCAATTG

[0423] AAAGATGGGAAACATCTGCCTTAGACCAATTGCCAGAATATGAAAATCATCTACCAAGCTTTGATGGATGTCTA

[0424] CTCCCAAATGGAAGAAAATGGCCAAAAAAGCTGATGCTCCAACCTACAGATTGGAATTTGCTATCGAAAACCG

[0425] TCAAGGCTTTGTTTCGTTCTTACTGGAAATTGCCAGATGGTCTAAGGAAAGATACATTCCAACTGTCGAAGAAT

[0426] ACATGTCTGTGGCTTTGGTTTCTTGCGGTGCTAAGACCATCTTGACCTGTTCCTTCGTCGGTATGGGTGACACTG

[0427] CCACGAGAGAAGTTTTCGAATGGGTTTCTAGCTCTCCATTGATTGTTCGCGCTTCCGATTTGATCAATGCTTTGGG

[0428] TGATGACATTGGTTCCCACGAAGAAGAACAAAAATGGGGTGACGCTGCTACCTACGTTGAATGTTACATGAAGG

[0429] AACACGGTGTTACCAAGCAAGAAGCTTACGCTGAAGCTCAAAAGCAAATCGACAACGCTAAGAAGGACTTGAA

[0430] CCAAGAAGCTCTAAGACCATTCCCAGTTCCAAGAACTTACATTACCAGAGTTGTTAACTTCACTCGTGCCATCAG

[0431] AGTCATTTACGCTGACTCCCACGATGGTTACACCCATCCAGAAAAGAAGATCAAGGGTTATATTACCTCCTTGCTGGTCCAACCAATCCCAATGTGA。

[0432] (SEQ ID NO:83)

[0433] MEVTRRSANYHPSVWGDKFLEYSSPDHLKNDSDELKNDAVTEKKLEKLKEEVKKMLVETVQKPQQALNLINEIQR

[0434] LGLSFHFEPEIEAALRQISVTYHELCESTNVDDLDNVALCFRILREHGHKVSADVFHKFMDSNGKLKGSFLNDAIGLL

[0435] SLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLYKELNRLGARYYISIYEKYDSHNKLLLEF

[0436] AKLDGNRMQKMYQHELAELTRDWKDLDFTNKLPFARDRIVEGYFNILGMYFEPECKDVREFLNRVFALISHVDDTY

[0437] DVYGTFEEVILFTHAIERWETSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADAPTYRLEFAIETVKALFRSYLEIA

[0438] RWSKERYIPTMEEYMSVALVSCGAKTILTNSFVGMGDTATREVFEWVSSSPLIVRASDLINALGDDIGGHEEEQKWG

[0439] DAATAVECYMKEHGVTKQEAYAEAQKQIDNAKKDLNQEALRPFPVPMTYITRVVNFTRAIRVIYADSDDGYTHPEKKIKGYITSLLVQPIPM。

[0440] (SEQ ID NO:84)

[0441] ATGGAAGTTACTAGAAGATCCGTAACTATCATCCATCTGTCTGGGGTGACAAATTCTTGGAATACTCTTTCCCAG

[0442] ACCATTTGAAGAATGATAGCGACGAATTGAAGAACGACGCTGTCACTGAAAAGAAGCTGGAAAAACTTAAGGA

[0443] AGAAGTCAAGAAGATGTTGGTGGAAACCGTCCAAGGCCACAACAAGCTTTGAACTTGATCAACGAAATCCAA

[0444] AGATTGGGTTTGAGTTTCCACTTCGAGCCTGAAATTGAAGCTGCTTTGAGACAAATCTCTGTTACCTACCACGAA

[0445] TTGTGCGAATCCACCAACGTCGATGATTTAGACAACGTTGCTTTGTGTTTCAGAATTCTCAGAGAACACGGTCAC

[0446] AAGGTTTCTGCTGATGTTTTCCACAAGTTCATGGACTCCAACGGTAAGTTGAAGGGTTCTTTCTTGAACGATGCT

[0447] ATCGGTTTGTTGTCCTTGTACGAGGCCACCCACTTCCGTGTCCATGGTGAAGACTTATTGGAAGATTTGTTGTCTT

[0448] TGACTACTTCCAGATTGGAATACTTGAAATCCCAAATGAAGTACCCATTGGAAGATGAAATCACCAGAGCTTTAA

[0449] AGCACCCATTGTACAAGGAATTAAATAGATTAGGTGCTAGATACTACATCTCGATTTACGAAAAGTATGATTCTCA

[0450] CAACAAATTGTTGCTGGAATTCGCTAAGTTGGATGGTAACAGAATGCAAAAGATGTACCAACACGAATTGGCTG

[0451] AACTTACACGTGACTGGAAGGACTTGGACTTCACTAACAAGCTACCATTCGCCAGAGACAGAATCGTTGAAGGT

[0452] TACTTCAACATCTTGGGTATGTATTTTGAACCAGAATGTAAGGATGTTAGAGAATTCTTAAACAGAGTTTTTGCCT

[0453] TGATTTCCCACGTTGACGACACTTACGACGTCTACGGTACTTTCGAGGAAGTTATCTTGTTCACCCATGCCATTGA

[0454] AAGATGGGAAACTTCTGCCTTGGACCAATTGCCAGAATATATGAAGATCATTTACCAAGCTTTGATGGACGTTTA

[0455] CTCCCAAATGGAAGAAGTTGGCTAAGAAGGCTGATGCTCCAACTTACAGATTGGAATTTGCTATCGAAACTG

[0456] TCAAGGCCTTATTCAGATCTTACTTGGAAATTGCTAGATGGTCTAAGGAACGTTACATTCCAACCATGGAAGAAT

[0457] ACATGTCTGTCGCTTTGGTTTCTTGTGGTGCCAAGACCATTTTGACTAACTCATTCGTTGGTATGGGTGACACTGC

[0458] TACTCGTGAAGTCTTTGAATGGGTTTCTTCCTCCCCTTTGATCGTCAGAGCTTCTGACTTGATCAATGCTCTGGGT

[0459] GACGATATTGGTGGTCACGAAGAAGAACAAAAGTGGGGTGATGCCGCTACCGCCGTCGAATGTTACATGAAAGA

[0460] ACACGGTGTTACCAAGCAAGAAGCTTACGCTGAGGCTCAAAAGCAAATTGACAACGCTAAGAAGGATTTGAAC

[0461] CAAGAAGCCTTAAGACCATTCCCAGTTCCAATGACCTACATTACCCGTGTTGTTAACTTCACCAGAGCTATCAGA

[0462] GTCATTTACGCTGACTCTGATGACGGTTACACTCACCCAGAAAAAAAAATCAAGGGCTACATCACTTCTTTGTTAGTTCAACCAATTCCAATGTGA。

[0463] (SEQ ID NO:87)

[0464] MEVTRRSANYHPSVWGDKFLEYSSPDHLKNDSDHLKNDAVTEKKLEKLKEEVKKMLVETVQKPQQALNLINEIQR

[0465] LGLSFHFEPEIEAALRQISVTYHELCESTNVDDLDNVALCFRILREHGHKVSCDVFHKFMDSNGKLKGSFLNDAIGLL

[0466] SLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLHKELNRLGARYYISIYEKYDSHNKLLLEF

[0467] AKLDGNRMQKMYQHELAELTRWWKDLDFTNKLPFARDRIVEGYFNILGMYFEPECKDVREFLNRVFALISHVDDT

[0468] YDVYGTFEEVILFTHAIERWETSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADAPTYRLEFAIETVKALFRSYLEI

[0469] ARWSKERYIPTMEEYMTVALVSCGAKTILTNSFVGMGDTATREVFEWVSSSPLIVRASDLINALGDDIGGHEEEQKK

[0470] GDAATAVECYMKEHGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPMTYITRVVHFTRAIHVIYADSDDGYTHPEKKIKGYITSLLVDPIPM。

[0471] (SEQ ID NO:88)

[0472] ATGGAAGTCACCAGAAGATCCGCTAACTACCATCCATCTGTCTGGGGTGACAAGTTCTTGGAATACTCCTCTCCA

[0473] GACCATTTGAAAAATGATTCAGACCACTTGAAGAACGATGCTGTCACTGAAAAGAAATTGGAGAAATTGAAGG

[0474] AAGAAGTTAAGAAGATGTTGGTCGAAACTGTTCAAGCCACAACAGGCTTTGAACTTGATCAACGAAATCCA

[0475] AAGATTAGGTTTGTCCTTCCACTTCGAACCTGAAATTGAAGCAGCTTTGAGACAAATCTCTGTCACTTACCACGA

[0476] ATTGTGTGAATCTACCAACGTCGATGATTTGGACAACGTTGCTCTTTGTTTCAGAATCTTGAGAGAACATGGTCA

[0477] CAAGGTTTCTTGTGATGTTTTCCATAAATTCATGGACTCTAACGGTAAGTTGAAAGGTTCTTTCTTAAACGACGCT

[0478] ATCGGTTGTTGTCCTTGTACGAAGCTACCCACTTCAGAGGTTCACGGTGAAGATTTGTTGGAAGACTTATTGTCT

[0479] TTGACCACATCCAGATTAGAATACTTGAAGTCTCAAATGAAGTACCCATTGGAAGATGAAATCACCAGAGCCCTT

[0480] AACACCCATTGCACAAGGAATTGAACAGATTGGGGGCTAGATACTACATCTCCATCTATGAAAAGTACGACTCC

[0481] CACAACAAGTGTGTGTTGGGAATTTGCTAAGTTAGATGGTAACAGAATGCAAAAGATGTACCAACACGAACTGGC

[0482] TGAATTGACCAGATGGTGGAAGGACCTAGACTTCACCAACAAGTTGCCATTCGCCAGAGACAGAATTGTTGAAG

[0483] GTTACTTCAACATTCTCGGTATGTATTTCGAACCAGAATGTAAGGATGTTAGAGAATTCTTGAACCGTGTTTTTGC

[0484] CTTATTTCTCACGTTGATGACACTTACGATGTTTACGGTACTTTCGAAGAAGTTATCTTATTCACCCACGCCATTG

[0485] AAAGGTGGGAAACCTCTGCTTTGGACCAATTGCCAGAATATATGAAGATTATCTACCAAGCTTTGATGGATGTCT

[0486] ACTCTCAAATGGAAGAGAAGTTGGCCAAGAAGGCTGATGCTCCAACTTACAGATTGGAATTCGCTATCGAAACC

[0487] GTTAAGGCCTTATTTAGATCTTACTTAGAAATTGCTCGTTGGAGTAAGGAAAGATACATCCCAACCATGGAAGAAT

[0488] ACATGACTGTCGCTCTAGTCTCCTGCGGTGCTAAGACTATCTTGACTAACTCTTTTGTCGGTATGGGTGACACCGC

[0489] CACTCGTGAAGTCTTCGAATGGGTTTCCTCTTCTCCATTGATTGTCAGAGCTTCAGATTTGATTAATGCTTTGGGT

[0490] GATGATATCGGTGGTCACGAAGAAGAACAAAAAGGGTGACGCTGCTACTGCTGTCGAATGTTACATGAAAGA

[0491] ACACGGTGTCACCAAGCAAGAAGCTTACGCCGAATTCCAAAAGCAAATTGACAACGCTTGGAAGGACTTGAAC

[0492] CAAGAAGCCTTGCGTCCTTTCCCAGTTCCATGACCTACATCACTCGTGTTGTGCATTTCACTAGAGCTATTCCACG

[0493] TCATTTACGCTGACTCCGACGACGGTTATACTCACCCAGAAAAGAAGATCAAGGGTTACATTACTTCTGTTGGTTGACCCAATTCCAATGTGA。

[0494] (SEQ ID NO:91)

[0495] MEVTRRSANYHPSVWGDKFLEYSSPDHLKNDSDHLKNDAVTEKKHEKLKEEVKKMLVETVQKPQQALNLINEIQR

[0496] LGLSFHFEPEIEALRQISVTYHEYCCSTNVDDLHNVALCFRILREHGHKVSCDVFHKFMDSNGKLKGSFLNDAIGLL

[0497] SLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLHKELNRLGARYYISIYEKYDSHNKLLLEF

[0498] AKLDGNRMQKMYQHELAELTRWWKDLDFTNKLPFARDRIVEGYFWILGMYFEPECKDVREFLNRVFALISHVDDT

[0499] YDVYGTFEEVILFTHAIERWETSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADCPTYRLEFAIETVKALFRSYLEI

[0500] ARWSKERYIPTMEEYMTVALVSVGYKTILTNSFVGMGDTATREVFEWVFSSPLIVRASDLIAALGDDIGGHEEEQKK

[0501] GDAATAVECYMKEHGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPMTYITRVVHFTRAIHVIYADSDDGYTRPEKKIKGYITSLLVDPIPM。

[0502] (SEQ ID NO:92)

[0503] ATGGAAGTCACTAGAAGATCTGCTAACTACCATCCATCTGTCTGGGGTGACAAGTTCTTAGAATACTCTTCTCCA

[0504] GACCACTTGAAGAACGATTCTGACCATTTGAAGAACGACGCTGTCACCGAAAAGAAGCACGAAAAGTTGAAAG

[0505] AAGAAGTCAAGAAGATGTTGGTTGAAACTGTCCAAAAGCCACAACAAGCTTTGAACTTGATCAACGAAATCCA

[0506] AAGATTGGGTTTGTCTTTCCACTTCGAACCTGAAATTGAAGCGGCTTTGAGACAAATCTCAGTTACTTACCACGA

[0507] ATACTGTTGTTCCACTAATGTCGACGATTTGCACAACGTTGCCCTTTGTTTCAGAATTTTAAGAGAACACGGTCA

[0508] CAAGGTTTCTTGCGATGTTTTCCATAAATTCATGGATTCCAACGGTAAGTTGAAGGGTTCCTTTTTGAATGATGCT

[0509] ATTGGTCGTTGTCTTTGTACGAAGCTACTCATTTCAGAGTCCACGGTGAAGATTTGTTGGAAGATCTCTTATCCT

[0510] TGACCACTTCTAGATTGGAATACTTGAAGTCCCAAATGAAATACCCATTGGAAGATGAAATCACCAGAGCTCTAA

[0511] AACACCCATTACACAAGAATTGAACCGCTTGGGTGCTCGTTACTACATTTCTATCTACGAAAAGTACGACTCTC

[0512] ACAACAAAATTGCTTTTGGAATTTGCTAAGTTGGATGGTAACAGAATGCAAAAGATGTACCAACACGAATTGGCT

[0513] GAATTGACTAGATGGTGGAAAGACTTGGATTTCACAAACAAGTTGCCATTCGCTAGAGACAGAATCGTGGAAGG

[0514] TTACTTCTGGATTCTTGGTATGTATTTTGAACCAGAATGTAAAGACGTCAGAGAATTCTTGAACAGAGTTTTTGCC

[0515] TTGATCTCCCACGTCGATGATACTTACGATGTCTACGGTACTTTCGAAGAAGTTATTCTTGTTCACTCACGCTATTG

[0516] AACGTTGGGAAACCTCTGCCTTAGACCAATTGCCAGAATACATGAAGATTATCTACCAAGCTTTGATGGACGTTT

[0517] ACTCTCAAATGGAAGAAAAGTTGGCCAAGAAGGCTGACTGTCCAACCTACAGATTGGAATTCGCTATCGAAACT

[0518] GTTAAGGCCTTGTTTCGTAGTTACTTGGAAATTGCCAGATGGTCTAAGGAAAGATACATCCCAACCATGGAAGAA

[0519] TATATGACTGTTGCTTTAGTCTCCGTCGGTTACAAGACCATCTTGACTAACTCTTTCGTTGGTATGGGTGACACTG

[0520] CTACCAGAGAAGTCTTCGAATGGGTTTTCTCCTCCCCATTAATTGTTAGAGCTTCTGACTTGATTGCTGCCTTGGG

[0521] TGATGACATCGGTGGACACGAAGAAGAACAAAAGAAGGGTGACGCTGCTACCGCCGTCGAATGTTACATGAAG

[0522] GAACATGGTGTTACCAAGCAAGAAGCTTACGCTGAATTCCAAAAGCAAATTGACAACGCTTGGAAGGATTTAAA

[0523] CCAAGAAGCTTTGCGTCCTTTCCCAGTTCCAATGACCTATATCACTAGAGTTGTTCACTTCACCAGAGCCATTCA

[0524] CGTTATCTATGCTGATTCCGACGACGGTTACACCAGACCAGAAAAAAAGATCAAGGGCTACATCACATCCCTATTGGTTGACCCAATTCCAATGTGA。

[0525] (SEQ ID NO:95)

[0526] MSLLVLSTSGSAPLTKKLEVKRRSANYKPSVWGDKFLEYQSPDALKADAEEAKKDAVEEKKLEKLSEEVAKMLVEH

[0527] VHKPQQALNLINEIERLGLSHHFLPEIEAALRQISVTYEELCRSLSVDDLSNVALCLRILREHGHDVSASVFTKFMDSN

[0528] GKLKASFLNDAIGLLSLYEATHFRVAGEDLLESLLSLTTSLLEALKSQLKYPLKDEIRMALKSPLAKEINRLGARYYIKI

[0529] YEKYSSHNKLLLEFAILDGNRMQKQYQRELAELTRDWKDLDTDNKLPFARDNIVSGFFLIYGMYSEPEMKDVREFL

[0530] NRVFDLISHVDDYYTVYGTFEEVILFTEAFERWTWSALDQLPEDMKIIFQALMDVYSQEEEKLAKKDDAPKYRLEF

[0531] AIETVKALTRSLLEIARWSKEREIPTLEEYMKVALVSCGFKTILTCSFVGMGTRATREVFEWVSSSPLIVRASELIAML

[0532] GDDIGAHEEEQKEGDAATAIECYMKEYGVTKEEAYAEFQKEIDEAWKDLNQEALRPFPVPWSYIDRVVNLTRAWHRIYADDHDGYTYPEKKIKGWINSLFHTPIPA。

[0533] (SEQ ID NO:96)

[0534] ATGTCTCTCTTGGTCTTGTCCACATCCGGTTCTGCTCCATTGACCAAGAAGTTGGAAGTCAAGAGAAGATCTGCT

[0535] AACTACAAGCCATCTGTCTGGGGTGACAAGTTCTTGGAGTACCAATCTCCAGACGCATTGAAGGCTGACGCTGA

[0536] AGAAGCTAAGAAAGATGCTGTCGAAGAAAAGAAGTTGGAAAAATTGTCTGAAGAAGTTGCTAAGATGTTGGTT

[0537] GAACACGTCCACAAGCCACAACAAGCTTTGAATTTGATCAACGAAATTGAACGTTTGGGTTTGTCTCATCACTTT

[0538] TTGCCAGAAATCGAAGCCGCCTTGAGACAAATTTCCGTCACTTACGAAGAATTGTGTCGTTCTTTGAGTGTCGAC

[0539] GACTTATCTAACGTTGCTTTATGCTTGAGAATCCTGCGTGAACACGGTCACGATGTCTCCGCCTCTGTTTTCACCA

[0540] AATTCATGGACTCCAACGGTAAGTTGAAGGCTTCTTTCTTGAACGATGCTATCGGTTTGCTTTCCTTGTACGAAG

[0541] CTACTCATTTCAGAGTTGCCGGTGAAGATTTGTTGGAATCTTTATTGTCTTTGACCACTTCCTTGTTAGAAGCCTT

[0542] GAAGTCCCAATTGAAGTACCCATTGAAAGATGAAATCAGAATGGCTTTGAAGTCCCCTCTGGCCAAGGAAATCA

[0543] ACAGATTGGGTGCTAGATACTACATCAAGATCTACGAAAAGTACTCCTCTCACAACAAGTTATTGTTGGAATTCG

[0544] CCATTTTGGATGGTAACAGAATGCAAGGCAATACCAAAGAGAATTGGCTGAATTAACCAGAGACTGGAAGGAC

[0545] CTAGACACTGACAACAAGTTGCCATTTGCCAGAGATAACATCGTCTCTGGTTTCTTCTTGATTTACGGCATGTACT

[0546] CTGAACCAGAAATGAAGGATGTCAGAGAGTTCTTAAATAGAGTCTTCGACCTGATCTCCCACGTTGATGACTATT

[0547] ACACTGTTTACGGTACCTTTGAAGAAGTTATCTTGTTCACTGAAGCTTTCGAAAGATGGACCTGGTCTGCCTTGG

[0548] ACCAATTACCAGAAGACATGAAAATCATCTTCCAAGCTTTGATGGATGTCTACTCTCAAGAAGAAGAAAAGCTC

[0549] GCTAAAAAAGGATGATGCTCCAAAGTACAGATTGGAATTCGCTATTGAAACCGTTAAGGCTTTGACCAGATCCTTG

[0550] CTCGAAATCGCTAGATGGTCCAAGGAAAGAGAAATCCCAACTTTGGAAGAATATATGAAGGTTGCTTTAGTTTCT

[0551] TGTGGTTTCAAGACCATCTTGACTTGTTCTTTCGTTGGTATGGGTACTCGTGCTACCAGAGAAGTCTTCGAATGG

[0552] GTTTCATCTTCTCCTTTGATTGTCAGAGGCTTCCGAATTGATCGCTATGTTGGGTGACGATATTGGTGCTCACGAAG

[0553] AAGAACAAAAGGAAGGTGATGCTGCAACTGCCATTGAATGTTACATGAAGGAAGAATACGGTGTTACCAAGGAAGA

[0554] AGCTTACGCTGAATTTCAAGGGAAATTGACGAAGCCTGGAAAGATTTGAACCAAGAAGCCCTCAGACCATTCC

[0555] CAGTTCCATGGTCTTACATTGACCGTGTTGTTAACTTGACTAGAGCTTGGCACAGGATTTATGCTGACGACCATGACGTTACACCTACCCAGAAAAGAAGATTAAGGGTTGGATTAACTCTTTATTCCACACTCCAATTCCAGCTTGA。(SEQ ID NO:99)

[0556] MSLLVLSTSGSAPLTKSLEVKRRSANYKPSVWGDKFLEYSSPDALKADAEEAKKDAVEEKKLEKLKEEVAKMLVET

[0557] VHKPQQALNLINEIQRLGLSHHFLPEIEAALRQISVTYEELCRSLSVDDLSNVALCLRILREHGHDVSASVFTKFMDSN

[0558] GKLKASFLNDAIGLLSLYEATHFRVAGEDLLESLLSLTTSLLEALKSQLKYPLEDEIRRALKSPLAKEINRLGARYYIKI

[0559] YEKYSSHNKLLLEFAILDGNRMQKQYQRELAELTRDWKDLDFDNKLPFARDNIVEGFFLIYGMYSEPEMKDVREFL

[0560] NRVFDLISHVDDYYTVYGTFEEVILFTEAFERWTWSALDQLPEDMKIIFQALMDVYSQEEEKLAKKADAPKYRLEF

[0561] AIETVKALTRSLLEIARWSKERYIPTMEEYMKVALVSCGFKTILTCSFVGMGTRATREVFEWVSSSPLIVRASELIAML

[0562] GDDIGAHEEEQKEGDAATAIECYMKEYGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPWSYIDRVVNLTRAWHRIYADDHDGYTYPEKKIKGWITSLFVTPIPA。

[0563] (SEQ ID NO:100)

[0564] ATGTCTCTATTGGTCTTGTCTACCTCTGGTTCTGCTCCATTGACTAAGAGCTTAGAAGTCAAGAGAAGATCCGCTA

[0565] ACTACAAGCCATCTGTCTGGGGTGACAAGTTTTTGGAATATAGCTCTCCAGATGCTTTAAAGGCTGATGCTGAAG

[0566] AAGCCAAGAAGGATGCTGTTGAAGAAAAAAAATTAGAAAAGTTGAAGGAAGAAGTGGCTAAGATGTTGGTGG

[0567] AAACTGTCCACAAGCCACAACAAGCTCTGAACTTGATCAACGAAATCCAAAGATTGGGTCTATCCCATCATTTCT

[0568] TGCCAGAAATTGAAGCTGCTTTGCGTCAAATTTCCGTTACTTACGAAGAATTATGCAGATCTTTGTCAGTCGATGA

[0569] TTTGTCCAACGTTGCTTTGTGTTTGCGTATTTTGAGAGAACACGGTCACGATGTCTCTGCTTCCGTCTTCACCAA

[0570] GTTCATGGATTCTAACGGTAAGTTAAAGGCTTCTTTCTTGAATGACGCTATTGGTTTGTTGTCTTTGTACGAAGCT

[0571] ACCCACTTCAGAGTCGCTGGTGAAGACTTGTTGGAATCTTTGCTCAGTTTGACTACCTCCTTGTTGGAAGCCCTT

[0572] AAATCTCAATTGAAATACCCATTGGAAGATGAAATCAGAAGAGCCTTGAAGTCTCCATTGGCTAAGGAAATCAA

[0573] CCGGTTAGGTGCCAGATACTACATTAAGATTTACGAAAAGTACTCATCTCACAACAAGTTGTTACTCGAATTCGC

[0574] CATATTGGATGGTAACAGAATGCAAAAGCAATACCAAAGAGAATTGGCTGAATTGACACGTGACTGGAAGGATC

[0575] TAGATTTCGATAATAAGTTGCCTTTTGCCAGAGACAACATTGTCGAAGGTTTCTTCTTGATTTATGGTATGTACTCT

[0576] GAACCAGAAATGAAGGACGTTAGAGAATTTTTGAACAGAGTTTTCGACTTGATCTCCCATGTTGACGACTACTAC

[0577] ACCGTTTACGGTACTTTCGAAGAAGTTATCCTATTCACTGAAGCCTTCGAAAGATGGACCTGGTCCGCCTTGGAC

[0578] CAATTGCCAGAGGACATGAAAATCATCTTCCAAGCCTTGATGGACGTCTACTCCCAAGAAAGAAAAGCTAGC

[0579] TAAGAAGGCTGACGCCCCCAAAGTACAGATTGGAATTCGCTATTGAAACTGTCAAAGCTTTGACCAGATCTTTATT

[0580] GGAAATCGCTCGTTGGTCTAAGGAAAGATACATTCCAACCATGGAAGAATATATGAAGGTTGCTTTGGTTTCTTG

[0581] TGGTTTCAAGACCATCTTGACTTGTTCCTTCGTTGGTATGGGTACCAGAGCTACTAGGGAAGTTTTTGAATGGGT

[0582] TTCCTCTTCCCCTCTGATCGTCAGAGCCTCCGAATTGATTGCTATGTTGGGCGATGACATCGGTGCTCACGAAGA

[0583] AGAAAAAAGAAGGTGATGCTGCTACTGCTATCGAATGTTACATGAAGGAATACGGTGTTACCAAGCAAGAAG

[0584] CTTACGCCGAATTCCAAAAAACAAATTGACAAGCCTTGGAAGGACTTGAACCAAGAAGCATTAAGACCATTCCCA

[0585] GTTCCATGGTCTTACATCGACAGAGTTGTTAACCTAACTAGAGCTTGGCACAGAATCTACGCTGACGACCACGACGGTTACACCTACCCAGAAAAGAAGATCAAGGGTTGGATTACTTCTTTGTTCGTCACTCCAATCCCAGCTTGA。

[0586] (SEQ ID NO:103)

[0587] MSLLVLSTSGSAPLTKSSEVKRRSANYKPSVWGDKFLEYSSPDALKADSEEAKKDAVEEKKLEKLKEEVAKMLVET

[0588] VQKPQQALNLINEIQRLGLSHHFLPEIEAALRQISVTYEELCRSLSVDDLSNVALCFRILREHGHDVSASVFTKFMDSN

[0589] GKLKGSFLNDAIGLLSLYEATHFRVAGEDLLESLLSLTTSRLEALKSQLKYPLEDEITRALKSPLAKEINRLGARYYIKI

[0590] YEKYSSHNKLLLEFAILDGNRMQKQYQRELAELTRDWKDLDFDNKLPFARDRIVEGFFLIYGMYSEPEMKDVREFL

[0591] NRVFDLISHVDDTYTVYGTFEEVILFTEAFERWTWSALDQLPEDMKIIYQALMDVYSQEEEKLAKKADAPKYRLEF

[0592] AIETVKALTRSLLEIARWSKERYIPTMEEYMKVALVSCGYKTILTCSFVGMGTRATREVFEWVSSSPLIVRASELIAML

[0593] GDDIGAHEEEQKEGDAATAIECYMKEYGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPWSYITRVVNLTRAWHRIYADDHDGYTYPEKKIKGWITSLFVTPIPA。

[0594] (SEQ ID NO:104)

[0595] ATGTCTTTGTTGGTCTTGTCCACTTCCGGTTCAGCTCCATTGACTAAATCTTCTGAAGTCAAGAGAAGATCCGCT

[0596] AACTACAAGCCATCCGTCTGGGGTGACAAGTTTCTTAGAATATAGTTCTCCAGACGCCCTCAAAGCTGATTCTGAG

[0597] GAAGCCAAAAAGGATGCTGCTGTCGAAGAAAAGAAATTGGAAAAGTTGAAGGAAGAGGTCGCTAAGATGTTGGTT

[0598] GAAACCGTTCAAGCCACAACAAGCTTTGAATTTAATTAACGAAATCCAAACGTTTGGGTTTGAGCCATCACTT

[0599] CTTGCCTGAAATCGAAGCTGCTTTAAGACAAATCTCCGTTACCTACGAAGAATTGTGCAGATCCTTGTCTGTCGA

[0600] TGATTTATCCAACGTTGCTTTGTGTTTCAGAATCTTGAGAGAACACGGTCACGATGTCTCCGCCTCTGTCTTTACC

[0601] AAGTTCATGGACAGTAACGGTAAGTTGAAGGGTTCTTTCTTGAACGACGCTATCGGTTTGTTATCCTTGTACGAA

[0602] GCTACCCATTTCAGAGTCGCTGGTGAAGACTTGTTGGAATCTTTGTTGTCTTTAACAACTTCCAGATTGGAAGCT

[0603] TTGAAGTCTCAATTGAAATACCCATTGGAAGATGAAATTACTAGAGCTCTAAAATCTCCACTAGCCAAGGAAATT

[0604] AATCGGTTAGGTGCCAGATACTACATTAAGATCTATGAAAAGTACTCTTCCCACAACAAGCTTTTGCTAGAATTTG

[0605] CTATTCTAGATGGTAACAGAATGCAAAAGCAATACCAACGTGAATTGGCTGAATTGACCCGTGACTGGAAGGAC

[0606] TTGGATTTCGACAACAAGTTGCCTTTTGCCAGAGACAGAATTGTTGAAGGCTTCTTCCTGATTTACGGTATGTAC

[0607] TCTGAACCAGAAATGAAGGATGTCAGAGAATTTTTGAACCGTGTTTTCGATTTGATCTCTCACGTTGACGACACT

[0608] TACACCGTCTACGGTACTTTCGAAGAAGTTATTTTATTCACTGAAGCTTTCGAAGATGGACCTGGTCTGCTTTG

[0609] GACCAATTGCCAGAAGACATGAAAATCATCTACCAAGCTTTGATGGATGTCTACTCCCAAGAAGAAGAAAAGTT

[0610] AGCTAAGAAGGCTGACGCCCCAAAGTACAGATTGGAATTCGCCATTGAAACTGTTAAGGCCTTGACCCGTTCGT

[0611] TACTTGAAATCGCTAGATGGTCCAAGGAACGTTTACATCCCAACCATGGAAGAATACATGAAGGTTGCTTTGGTT

[0612] CTTGTGGTTACAAGACCATCCTGACTTGTTCTTTCGTTGGTATGGGTACCAGAGCTACCAGAGAAGTCTTCGAAT

[0613] GGGTTTCCTCCTCCCATTAATTGTTAGAGCCTCTCGAATTGATCGCTATGTTGGGTGATGACATTGGTGCTCACGA

[0614] AGAAGAACAAAAGGAAGGTGATGCTGCCACTGCTATTGAATGTTACATGAAGGAATACGGTGTTACCAAGCAAG

[0615] AAGCTTACGCTGAATTCCAAAAACAAATTGACAACGCTTGGAAGGACTTGAACCAAGAAGCTTTAAGACCATTC

[0616] CCAGTTCCATGGTCTTACATCACTAGAGTTGTTAACTTGACAAGAGCTTGGCACAGAATCTACGCAGATGACCACGACGGTTACACTTATCCAGAAAAGAAGATCAAGGGTTGGATCACCTCTTTGTTCGTGACTCCAATTCCAGCTTGA。(SEQ ID NO:107)

[0617] MSLLVLSTSGSAPLTKSSEVKRRSANYKPSVWGDKFLEYSSPDALKADSDEAKKDAVEEKKLEKLKEEVAKMLVET

[0618] VQKPQQALNLINEIQRLGLSHHFEPEIEAALRQISVTYHELCRSLSVDDLSNVALCFRILREHGHDVSASVFTKFMDS

[0619] NGKLKGSFLNDAIGLLSLYEATHFRVHGEDLLESLLSLTTSRLEALKSQLKYPLEDEITRALKHPLAKEINRLGARYYI

[0620] KIYEKYDSHNKLLLEFAILDGNRMQKMYQRELAELTRDWKDLDFTNKLPFARDRIVEGFFLIYGMYSEPEMKDVRE

[0621] FLNRVFDLISHVDDTYTVYGTFEEVILFTEAFERWEWSALDQLPEDMKIIYQALMDVYSQEEEKLAKKADAPKYRL

[0622] EFAIETVKALTRSLLEIARWSKERYIPTMEEYMKVALVSCGYKTILTCSFVGMGTRATREVFEWVSSSPLIVRASELIA

[0623] MLGDDIGAHEEEQKEGDAATAIECYMKEYGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPWSYITRVVNLTRAIHRIYADDHDGYTYPEKKIKGYITSLFVTPIPA。

[0624] (SEQ ID NO:108)

[0625] ATGTCCCTGTTGGTCTTGTCTACTTCTGGTTCCGCTCCATTGACTAAGTCTTCCGAAGTTAAGAGAAGATCTGCTA

[0626] ACTACAAGCCATCTGTCTGGGGTGACAAATTCTTGGAATACTCTTCTCCAGACGCCTTGAAAGCCGATTCTGACG

[0627] AAGCTAAGAAAGATGCCGTCGAAGAAGAAGAAGTTGGAAAAGTTGAAGGAAGAAGTCGCTAAGATGTTGGTAG

[0628] AACTGTCCAAGGCCACAACAAGCGCTTAACTTGATTAACGAAATCCAAAGATTGGGTTTGTCCCATCACTTT

[0629] GAACCAGAAAATTGAAGCTGCTTTGAGACAAATCTCCGTTACTTACCACGAATTATGTCGTTCTTTGTCTGTTGAC

[0630] GATCTTTCAAACGTTGCCTTGTGTTTCAGAATTCTACGTGAACACGGTCACGACGTTAGTGCTTCCGTTTTCACC

[0631] AAGTTCATGGATTCCAATGGAAAGCTCAAGGGTTCTTTCTTGAACGATGCCATTGGTTTATTGTCCTTGTACGAG

[0632] GCTACTCATTTCAGGTCCACGGTGAAGATTTGTTAGAATCCTTGTTGTCTTTGACTACCTCCAGATTGGAAGCCT

[0633] TGAAGTCCCAATTGAAGTACCCATTGGAAGATGAAATCACTAGAGCTTTGAAGCACCCATTGGCCAAGGAAATC

[0634] AACCGTTTGGGCGCTCGTTACTACATCAAGATTTACGAAAAATACGATTCTCACAACAAATTGTTGTTGGAATTT

[0635] GCTATCTTGGACGGTAACAGAATGCAAAAGATGTACCAAAGAGAATTGGCTGAACTGACAAGAGACTGGAAGG

[0636] ATTTGGATTTCACCAACAAGTTACCTTCGCCAGAGACAGAATCGTTGAAGGTTTCTTCTTGATCTACGGTATGTA

[0637] CTCAGAGCCAGAAATGAAGGATGTCAGAGAATTCTTAAATAGAGTTTTCGACTTGATCTCTCATGTTGATGACAC

[0638] TTACACTGTTTACGGTACTTTCGAAGAAGTCATCTTATTCACTGAAGCTTTCGAAAGATGGGAATGGTCTGCTCT

[0639] CGACCAATTGCCAGAAGACATGAAGATTATTTACCAGGCTTTGATGGACGTCTACAGTCAAGAAGAAGAAAAAT

[0640] TAGCAAAGAAGGCTGATGCTCCAAAGTACAGATTGGAATTCGCTATCGAAACCGTCAAGGCTCTAACTAGATCCT

[0641] TGTTGGAAATTGCTCGTTGGTCCAAGGAAAGATATATTCCAACCATGGAAGAATATATGAAGGTTGCTTTAGTCTC

[0642] TTGTGGTTATAAGACCATTTTGACCTGCTCTTTCGTCGGTATGGGTACCAGAGCTACCCGTGAAGTTTTTGAATGG

[0643] GTTTCCTCCTCTCCTTTGATCGTTAGAGCTTCTGAATTAATCGCTATGTTAGGTGATGACATCGGTGCTCACGAAG

[0644] AAGAACAAAAGGAAGGTGACGCCGCCACTGCTATTGAATGTTACATGAAAGAATACGGTGTTACCAAGCAAGA

[0645] AGCTTACGCAGAATTCCAAAAGCAAATTGACAACGCTTGGAAGGACTTGAACCAAGAAGCTTTAAGACCATTCC

[0646] CAGTTCCATGGTCTTACATTACCAGAGTTGTCAACTTGACCAGAGCCATTCACAGAATCTACGCTGACGACCACGATGGTTACACGTACCCAGAAAAGAAGATTAAGGGTTACATCACCTCTTTGTTTGTTACTCCAATCCCAGCTTGA。(SEQ ID NO:111)

[0647] MSLLVLSTSGSAPTTKSSEVKRRSANYKPSVWGDKFLEYSSPDALKADSDEAKKDAVTEKKLEKLKEEVAKMLVET

[0648] VQKPQQALNLINEIQRLGLSFHFEPEIEAALRQISVTYHELCRSTNVDDLSNVALCFRILREHGHDVSADVFTKFMDS

[0649] NGKLKGSFLNDAIGLLSLYEATHFRVHGEDLLESLLSLTTSRLEALKSQLKYPLEDEITRALKHPLAKEINRLGARYYI

[0650] KIYEKYDSHNKLLLEFAILDGNRMQKMYQHELAELTRDWKDLDFTNKLPFARDRIVEGFFLIYGMYSEPEMKDVRE

[0651] FLNRVFDLISHVDDTYDVYGTFEEVILFTEAFERWEWSALDQLPEDMKIIYQALMDVYSQEEEKLAKKADAPKYRL

[0652] EFAIETVKALTRSLEIARWSKERYIPTMEEYMKVALVSVGYKTILTNSFVGMGTRATREVFEWVSSSPLIVRASELIA

[0653] MLGDDIGAHEEEQKKGDAATAIECYMKEYGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPWSYITRVVNFTRAIHRIYADDHDGYTYPEKKIKGYITSLFVTPIPA。

[0654] (SEQ ID NO:112)

[0655] ATGTCTTGTTAGTTTTGTCCACATCTGGTAGCGCTCCAACTACCAAGTCTTCCGAAGTTAAGAGAAGATCTGCT

[0656] AACTACAAGCCAAGTGTCTGGGGTGACAAGTTTTTAGAGTACAGCTCTCCAGACGCTTTGAAAGCCGACTCCGA

[0657] TGAAGCCAAAAAGGACGCTGTCACTGAAAAGAAGTTGGAAAAATTGAAGGAAGAAGTTGCCAAGATGTTGGT

[0658] CGAAACTGTTCAAGGCCACAACAAGCTTTGAACTTGATCAACGAAATCCAAAGACTTGGTTTGTCCTTCCACT

[0659] TCGAACCAGAAATCGAAGCTGCCTTAAGACAAATATCCGTTACCTACCATGAATTATGTCGTTCCACCAACGTTG

[0660] ATGATTTGTCAAATGTCGCCTTGTGTTTCAGGATCTTGAGAGAACACGGTCACGACGTCTCTGCCGATGTCTTTA

[0661] CTAAATTCATGGACTCCAACGGTAAGTTGAAGGGTTCTTTCTTGAACGATGCTATTGGTCTACTGTCTTTGTACGA

[0662] AGCCACTCATTTCAGAGTCCATGGTGAAGATTTGTTGGAATCTTTGTTGTCATTGACCACTTCCAGACTAGAGGC

[0663] TCTGAAGTCCCAATTGAAGTATCCATTAGAAGACGAAATTACCAGAGCTTTGAAGCACCCATTGGCTAAGGAAAT

[0664] AAACCGTTTGGGTGCCAGATACTACATCAAGATTTACGAAAAGTACGACTCCCACAACAAGTTATTGTTGGAATT

[0665] CGCTATCTTGGACGGTAACAGAATGCAAAAGATGTACCAACACGAATTGGCAGAATTGACCAGAGACTGGAAG

[0666] GATTTGGATTTCACCAACAAGCTTCCTTTTGCCAGAGACAGAATTGTTGAAGGTTTCTTCTTGATTTACGGTATGT

[0667] ACTCTGAACCAGAAATGAAAGATGTTAGAGAATTCTTGAATAGAGTTTTCGACTTGATCTCTCACGTTGACGACA

[0668] CTTACGATGCTACGGTACTTTTGAAGAAGTCATTTTGTTCACTGAAGCTTTCGAAAGATGGGAATGGAGTGCTT

[0669] TGGACCAATTACCAGAAGACATGAAGATCATTTACCAAGCTTTGATGGATGTTTATTCTCAAGAAGAAGAAAAGT

[0670] TGGCTAAGAAGGCTGACGCCCCAAAGTACAGATTAGAATTTGCCATTGAAACCGTCAAGGCTTTGACCAGATCC

[0671] TTGTGGAAATCGCTAGATGGTCTAAGGAACGTTACATTCCAACCATGGAAGAATACATGAAGGTTGCTTTGGTG

[0672] TCTGTTGGTTACAAGACCATCTTAACTAACTCTTTCGTCGGTATGGGTACCCGTGCTACCCGTGAAGTTTTCGAAT

[0673] GGGTTTCTTCTTCCCCATTGATTGTCAGAGCTTCTGAATTAATTGCTATGTTGGGCGACGATATCGGTGCTCACGA

[0674] AGAAGAACAAGAAGGGTGATGCTGCTACTGCTATCGAATGTTACATGAAGGAATATGGTGTCACCAAGCAAG

[0675] AAGCATATGCTGAATTCCAAGCAAATTGACAACGCTTGGAAGGACTTGAACCAAGAAGCTTTAAGACCATTC

[0676] CCAGTCCCATGGTCTTACATCACTAGAGTTGTTAACTTCACTAGAGCTATTCACAGAATCTACGCTGATGACCACGATGGTTACACTTACCCAGAAAAGAAAATCAAAGGTTACATTACGTCTTTGTTCGTTACTCCTATCCCAGCTTGA。(SEQ ID NO:115)

[0677] MSLLVLSTSGSAPTTKSSEVKRRSANYKPSVWGDKFLEYSSPDALKNDSDELKKDAVTEKKLEKLKEEVAKMLVET

[0678] VQKPQQALNLINEIQRLGLSFHFEPEIEAALRQISVTYHELCRSTNVDDLSNVALCFRILREHGHKVSADVFTKFMDS

[0679] NGKLKGSFLNDAIGLLSLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLAKEINRLGARYY

[0680] IKIYEKYDSHNKLLLEFAILDGNRMQKMYQHELAELTRDWKDLDFTNKLPFARDRIVEGYFLIYGMYFEPEMKDVR

[0681] EFLNRVFDLISHVDDTYDVYGTFEEVILFTEAFERWEWSALDQLPEDMKIIYQALMDVYSQEEEKLAKKADAPKYR

[0682] LEFAIETVKALTRSYLEIARWSKERYIPTMEEYMKVALVSVGYKTILTNSFVGMGDRATREVFEWVSSSPLIVRASELI

[0683] AMLGDDIGAHEEEQKKGDAATAIECYMKEYGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPWSYITRVVNFTRAIHRIYADSHDGYTYPEKKIKGYITSLFVTPIPA。

[0684] (SEQ ID NO:116)

[0685] ATGTCTTTGCTAGTCTTGTCTACTTCTGGTTCTGCTCCAACTACTAAGTCCTCCGAAGTTAAGAGAAGATCTGCTA

[0686] ACTACAAGCCATCTGTCTGGGGTGACAAGTTCTTGGAATACTCTTCTCCAGACGCTTTAAAGAACGACTCCGATG

[0687] AACTGAAGAAGGATGCTGTCACTGAAAAGAAGTTGGAAAAATTGAAGGAAGAAGTTGCTAAGATGTTGGTCGA

[0688] AACTGTTCAAGGCCACAACAAGCTTTAAACTTGATTAACGAAATCCAAAGATTGGGTTTGAGCTTCCACTTCG

[0689] AACCAGAAATCGAAGCTGCTTTGAGACAAATCTCTGTCACTTACCACGAATTGTGTCGTTCCACCAACGTCGAT

[0690] GATTTGTCCAATGTTGCTTTATGTTTCAGAATCTTGCGTGAACACGGTCACAAGGTCAGTGCCGATGTTTTCACC

[0691] AAATTCATGGACTCCAACGGTAAGTTGAAGGGTTCTTTCTTGAACGATGCCATTGGTTTGTTGTCTTGTACGAA

[0692] GCTACCCCATTTCAGAGTTCACGGTGAAGACTTGCTAGAAGATTTATTGTCCTTGACCACTTCCAGACTGGAATAT

[0693] TTGAAGTCTCAAATGAAATATCCATTAGAGGACGAAATCACTAGGGCTTTGAAGCACCCATTGGCCAAGGAAAT

[0694] CAACCGGTTGGGTGCCAGATACTACATCAAGATTTACGAAAAGTACGACTCTCACAACAAGTTGTTGTTGGAATT

[0695] TGCTATTTTGGATGGTAACAGAATGCAAAAAATGTACCAACACGAATTAGCTGAATTGACCAGAGACTGGAAAG

[0696] ACTTAGATTTCACCAATAAATTACCTTTCGCTAGAGATAGAATCGTTGAAGGTTACTTCTTAATATATGGTATGTAC

[0697] TTTGAACCAGAAATGAAGGACGTTAGAGAATTCTTGAACAGAGTTTTCGACTTGATCTCCCATGTTGACGACAC

[0698] TTACGATGTTTACGGTACCTTTGAAGAAGTTATCTTATTCACTGAAGCTTTCGAAAGATGGGAATGGTCTGCCTTG

[0699] GACCAATTGCCAGAAGACATGAAGATCATTTACCAAGCCTTGATGGATGTCTACTCCCAAGAAGAAGAAAAGTT

[0700] GGCTAAGAAGGCTGACGCTCCAAAGTACAGATTGGAATTTGCCATTGAAACCGTCAAGGCTCTAACCAGATCTT

[0701] ACTTGGAAATCGCTCGTTGGTCCAAGGAACGTTACATCCCAACCATGGAAGAATATATGAAGGTTGCCTTGGTTT

[0702] CTGTTGGTTACAAGACTATCTTGACTAACTCTTTTGTCGGTATGGGTGACAGAGCTACTAGAGAAGTCTTCGAAT

[0703] GGGTTTCCTCTTCTCCATTGATTGTCAGAGCTTCTGAATTGATTGCTATGTTGGGCGATGACATTGGTGCTCACGA

[0704] AGAAGAACAAAAGAAGGGTGATGCTGCCACAGCTATTGAATGTTACATGAAAGAGTACGGTGTTACCAAGCAA

[0705] GAAGCTTACGCTGAATTCCAAAAGCAAATTGACAACGCTTGGAAGGACTTGAACCAAGAAGCCTTAAGACCAT

[0706] TCCCAGTTCCATGGTCTTACATAACCAGAGTTGTCAACTTCACCAGAGCCATTCACAGAATTTACGCAGATTCTC

[0707] ATGACGGTTACACTTACCCTGAAAAGAAAATCAAAGGTTACATTACTTCACTATTCGTTACTCCAATCCCAGCTTGA。

[0708] (SEQ ID NO:119)

[0709] MSLNVLSTSGSAPTTKSSEVTRRSANYKPSVWGDKFLEYSSPDALKNDSDELKKDAVTEKKLEKLKEEVAKMLVET

[0710] VQKPQQALNLINEIQRLGLSFHFEPEIEAALRQISVTYHELCRSTNVDDLSNVALCFRILREHGHKVSADVFTKFMDS

[0711] NGKLKGSFLNDAIGLLSLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLAKEINRLGARYY

[0712] IKIYEKYDSHNKLLLEFAILDGNRMQKMYQHELAELTRDWKDLDFTNKLPFARDRIVEGYFLIYGMYFEPECKDVRE

[0713] FLNRVFALISHVDDTYDVYGTFEEVILFTEAFERWEWSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADAPTYRL

[0714] EFAIETVKALTRSYLEIARWSKERYIPTMEEYMKVALVSVGYKTILTNSFVGMGDRATREVFEWVSSSPLIVRASDLIA

[0715] MLGDDIGAHEEEQKKGDAATAVECYMKEHGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPWSYITRVVNFTRAIHRIYADSHDGYTYPEKKIKGYITSLFVTPIPM。

[0716] (SEQ ID NO:120)

[0717] ATGTCATTAAACGTCCTCTCTACTTCTGGTTCTGCCCCAACTACTAAGTCATCTGAAGTTACTAGAAGATCTGCTA

[0718] ACTACAAGCCATCTGTCTGGGGTGACAAGTTCTTGGAGTATTCCTCTCCAGACGCTTTGAAGAACGACTCCGAT

[0719] GAATTGAAGAAAGATGCCGTCACTGAAAAAAAGTTGGAAAAGTTGAAGGAAGAAGTCGCTAAGATGTTGGTTG

[0720] AAACCGTTCAAAAGCCACAACAAGCCTTGAACTTGATCAACGAAATCCAAAGATTGGGATTGTCTTTCCACTTT

[0721] GAACCAGAAATTGAAGCCGCTTTGAGACAAATCTCCGTTACTTACCACGAATTATGCAGATCCACTAATGTCGAT

[0722] GATTTGTCTAACGTTGCTTTGTGTTTCAGAATCCTAAGAGAACATGGTCACAAGGTTTCTGCTGATGTTTTTACCA

[0723] AGTTCATGGACTCCAACGGTAAGCTAAAAGGTTCCTTCTTAAACGATGCTATCGGTTTGTTGTCTTTGTACGAAG

[0724] CTACTCATTTCAGAGTTCACGGTGAAGATTTGTTGGAAGACTTGTTGTCTCTGACTACTTCCAGACTAGAATACT

[0725] TGAAGTCCCAAATGAAGTACCCTTTGGAAGACGAAATCACACGTGCTTTGAAGCACCCATTAGCCAAGGAGATC

[0726] AACAGATTGGGTGCCCGTTACTACATCAAGATTTACGAAAAATACGATTCCCACAACAAGCTGTTGCTTGAATTT

[0727] GCTATTCTTGGACGGTAACAGAATGCAAAAAATGTACCAACACGAATTGGCTGAATTAACCAGGGATTGGAAGGA

[0728] TTTGGATTTCACCAACAAATTGCCATTCGCTAGAGACAGAATTGTGGAAGGTTACTTCTTGATTTACGGTATGTAT

[0729] TTTGAACCTGAATGTAAGGACGTCCGTGAATTCTTGAATCGTGTTTTCGCTTTGATCTCTCATGTTGACGACACTT

[0730] ACGACGTTTACGGTACTTTCGAAGAAGTCATTTTATTCACTGAAGCTTTCGAAAGATGGGAATGGAGCGCATTGG

[0731] ACCAATTGCCAGAATACATGAAAATCATCTATCAAGCTTTGATGGATGTCTACTCTCAAATGGAAGAAAAATTGG

[0732] CTAAGAAGGCTGATGCTCCAACCTACAGATTAGAGGTTTGCCATCGAAACTGTTAAGGCCTTGACCAGATCTTACC

[0733] TAGAAATTGCCAGATGGTCCAAGGAAAGATACATCCCAACCATGGAAGAATATATGAAGGTTGCTTTAGTTTCCG

[0734] TCGGTTACAAGACCATCTGACTAACTCTTTCGTCGGTATGGGCGACAGAGCCACCCGTGAAGTTTTCGAATGGG

[0735] TTAGTTCTTCCCCATTGATTGTCAGAGCTTCTGACTTGATTGCTATGTTGGGTGATGACATTGGTGCTCACGAAGA

[0736] AGAACAAGAAGGGTGACGCTGCTACCGCTGTCGAATGTTACATGAAGGAACACGGTGTTACCAAGCAAGAA

[0737] GCTTACGCTGAATTCCAAGCAAATTGACAACGCTTGGAAGGACTTGAACCAAGAAGCTTTAAGACCATTCCC

[0738] AGTTCCATGGTCCTACATCACCAGAGTTGTCAACTTCACCAGAGCTATTCACAGAATCTACGCTGACTCTCACGATGGTTACACTTACCCGGAAAAGAAGATCAAGGGTACATTACCTCTTTGTTCGTCACCCCAATTCCAATGTGA。(SEQ ID NO:123)

[0739] MSLNVLSTSGSAPTTKSSEVTRRSANYHPSVWGDKFLEYSSPDALKNDSDELKNDAVTEKKLEKLKEEVKKMLVET

[0740] VQKPQQALNLINEIQRLGLSFHFEPEIEAALRQISVTYHELCRSTNVDDLSNVALCFRILREHGHKVSADVFHKFMDS

[0741] NGKLKGSFLNDAIGLLSLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLAKEINRLGARYY

[0742] ISIYEKYDSHNKLLLEFAKLDGNRMQKMYQHELAELTRDWKDLDFTNKLPFARDRIVEGYFLIYGMYFEPECKDVR

[0743] EFLNRVFALISHVDDTYDVYGTFEEVILFTHAFERWETSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADAPTYR

[0744] LEFAIETVKALFRSYLEIARWSKERYIPTMEEYMKVALVSVGYKTILTNSFVGMGDTATREVFEWVSSSPLIVRASDLI

[0745] AMLGDDIGAHEEEQKKGDAATAVECYMKEHGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPWTYITRVVHFTRAIHRIYADSHDGYTYPEKKIKGYITSLFVTPIPM。

[0746] (SEQ ID NO:124)

[0747] ATGTCTTTGAACGTGTTGTCCACTTCTGGTTCCGCCCCAACTACTAAGTCTTCTGAAGTTACCAGAAGATCCGCT

[0748] AACTACCACCCATCTGTCTGGGGTGACAAGTTTTTAGAATACAGCTCCCCAGATGCCTTGAAGAATGACTCTGAC

[0749] GATTGAAGAACGACGCTGTTACTGAAAGAAACTAGAAAAGCTAAAAGAAGAAGTCAAGAAGATGTTGGTTG

[0750] AAACTGTTCAAAAGCCACAACAAGCTTTGAACTTAATCAACGAAATCCAAAGATTGGGTTTGTCTTTCCATTTCG

[0751] AACCAGAAAATTGAAGCCGCTTTGAGACAAATCTCCGTCACTTACCATGAACTTTGCCGTTCTACCAATGTTGACG

[0752] ACTTGTCAAACGTTGCCTTGTGTTTCCGTATCTTGAGAGAACACGGTCACAAGGTTTCTGCTGATGTTTTCCACA

[0753] AGTTCATGGACTCTAACGGTAAGTTGAAGGGTTCTTTCTTGAACGATGCCATTGGTTTGTTGTCCTTGTACGAAG

[0754] CTACCCACTTCAGAGTTCATGGTGAAGACTTGTTGGAAGATTTATTGTCCTTGACTACCTCTAGATTGGAATACTT

[0755] GAAATCCCAAATGAAATACCCTTTGGAAGATGAAATCACCAGAGCCTTAAAGCATCCATTGGCCAAGGAAATTA

[0756] ACAGATTGGGCGCTAGATACTACATTTCTATCTACGAAAAGTACGACTCCCACAACAAATTGCTTTTGGAATTTGC

[0757] TAAGTTGGACGGTAACAGAATGCAAGATTGTACCAACACGAATTGGCTGAATTGACAAGAGACTGGAAGGAC

[0758] TTGGATTTCACTAACAAGCTGCCATTCGCCAGAGACAGAATTGTCGAAGGTTACTTCTTAATTTACGGTATGTATT

[0759] TTGAACCAGAGTGTAAGGACGTCAGAGAATTCTTGAACAGAGTCTTCGCTTTGATCTCTCACGTTGATGACACTT

[0760] ACGATGTTTACGGTACTTTCGAAGAAGTCATCTTGTTTACTCACGCTTTCGAAAGGTGGGAAACCTCTGCACTAG

[0761] ACCAATTGCCTGAATACATGAAAATCATCTACCAAGCTTTGATGGATGTCTACTCTCAAATGGAAGAAAAGTTGG

[0762] CTAAAAGGCTGATGCTCCAACCTACAGATTAGAATTCGCTATCGAAACTGTTAAGGCCTTATTCAGATCTTACTT

[0763] GGAAATCGCTAGATGGTCTAAGGAACGTTACATCCCCAACCATGGAAGAATATATGAAGGTTGCTTTGGTTTCTGT

[0764] CGGTTACAAGACTATTTTGACCAACTCCTTCGTTGGTATGGGTGACACCGCTACCCGTGAAGTTTTCGAATGGGT

[0765] TAGTTCCCTCCCCATTGATTGTTAGAGCTAGTGATTTGATTGCTATGTTGGGTGACGATATTGGTGCTCACGAAGAG

[0766] GAACAAAAAGAGGGTGATGCTGCTACTGCTGTCGAATGTTACATGAAGGAACACGGTGTTACCAAGCAAGAAG

[0767] CTTACGCTGAATTCCAAGCAAATTGACAACGCTTGGAAGGATTTGAACCAAGAAGCGTTAAGACCATTCCCA

[0768] GTTCCATGGACTTATATCACCCGTGTTGTCCACTTCACCAGAGCTATTCACAGAATCTATGCTGACTCACACGATGGTTACACTTACCCAGAAAAAAAGATCAAGGGTTACATAACTTCCCTCTTTGTTACTCCAATTCCAATGTGA。

[0769] (SEQ ID NO:127)

[0770] MSLNVLSTSGSAPTTKSSEVTRRSANYHPSVWGDKFLEYSSPDHLKNDSDHLKNDAVTEKKLEKLKEEVKKMLVET

[0771] VQKPQQALNLINEIQRLGLSFHFEPEIEAALRQISVTYHELCRSTNVDDLHNVALCFRILREHGHKVSCDVFHKFMDS

[0772] NGKLKGSFLNDAIGLLSLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLHKELNRLGARY

[0773] YISIYEKYDSHNKLLLEFAKLDGNRMQKMYQHELAELTRWWKDLDFTNKLPFARDRIVEGYFLIYGMYFEPECKDV

[0774] REFLNRVFALISHVDDTYDVYGTFEEVILFTHAFERWETSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADAPTY

[0775] RLEFAIETVKALFRSYLEIARWSKERYIPTMEEYMKVALVSVGYKTILTNSFVGMGDTATREVFEWVSSSPLIVRASDL

[0776] IAMLGDDIGGHEEEQKKGDAATAVECYMKEHGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPWTYITRVVHFTRAIHVIYADSDDGYTYPEKKIKGYITSLFVDPIPM。

[0777] (SEQ ID NO:128)

[0778] ATGTCTCTTAATGTCTTGTCCACTTCTGGTTCTGCTCCAACCACCAAGTCTTCTGAAGTTACCAGAAGATCCGCTA

[0779] ACTACCATCCATCTGTCTGGGGTGACAAGTTCTTGGAATATTCCTCTCCAGACCACTTGAAGAACGACTCAGATC

[0780] ATTTGAAGAACGATGCTGTCACTGAAAAAAAATTGGAAAAGCTGAAGGAAGAAGTTAAGAAGATGTTGGTTGA

[0781] AACTGTTCAAAAGCCACAACAAGCTTTGAACTTGATCAACGAAATCCAAAGATTGGGTTTGTCTTTCCACTTCG

[0782] AACCAGAAATTGAAGCTGCTTTGCGTCAAATCTCTGTCACGTACCACGAATTGTGCAGATCTACCAACGTCGATG

[0783] ACTTGCACAACGTTGCTTTGTGTTTCAGAATCTTACGTGAACACGGTCACAAGGTTCCTGTGATGTTTTCCATA

[0784] AGTTCATGGATTCCAACGGTAAGTTAAAGGGTTCCTTCTTGAACGATGCCATCGGTTTGTTGAGCTTGTACGAAG

[0785] CTACCCACTTCAGAGGTTCACGGTGAAGACTTATTGGAAGACCTTCTATCTTTGACTACCTCTAGATTAGAATACTT

[0786] GAAGTCCCAAATGAAGTACCCTCTCGAAGATGAAATCACAAGAGCTTTGAAGCACCCATTGCACAAGGAATTGA

[0787] ACCGTTTGGGTGCCCGTTACTACATCTCCATTTACGAAAAGTACGATTCTCACAACAAGTTGTTGTTGGAATTTG

[0788] CTAAGTTGGACGGTAACAGAATGCAAAAGATGTACCAACACGAATTGGCCGAACTAACTAGATGGTGGAAGGA

[0789] CTTGGATTTCACTAACAAATTGCCTTTCGCTAGAGACAGAATTGTTGAAGGTTATTTCTTGATCTACGGTATGTAC

[0790] TTCGAACCAGAATGTAAGGATGTTAGAGAATTCTTAAATAGAGTTTTCGCCTTGATCTCCCACGTCGATGACACCT

[0791] ACGACGTCTATGGTACTTTCGAAGAAGTCATTTTGTTCACTCACGCTTTCGAAAGATGGGAAACCTCTGCTCTCG

[0792] ACCAATTGCCAGAATATATGAAGATTATTTACCAAGCTTTGATGGATGTCTACTCTCAAATGGAAGAAAAAGTTGGC

[0793] CAAGAAAGCTGACGCTCCAACTTACAGACTAGAGTTTGCTATCGAAACTGTCAAGGCCTTATTTAGGTCTTACTT

[0794] GGAAATTGCCAGATGGTCTAAGGAAAGATACATTCCAACCATGGAAGAATACATGAAGGTCGCTTTAGTATCTGT

[0795] TGGTTACAAGACCATCTTGACCAACTCTTTCGTCGGTATGGGTGACACTGCTACCAGAGAAGTCTTTTGAATGGGT

[0796] TAGTTCTCTCCCCATTGATTGTCAGAGCTTCTGACTTGATTGCTATGCTTGGCGACGACATTGGTGGTCACGAAGA

[0797] AGAACAAAAGAAAGGTGACGCTGCCACGGCTGTTGAGTGTTACATGAAGGAACATGGTGTTACTAAGCAAGAA

[0798] GCTTACGCTGAATTCCAAAAGCAAATTGACAACGCTTGGAAAGATTTGAACCAAGAAGCATTAAGACCATTCCC

[0799] AGTTCCATGGACTTACATTACCCGTGTTGTCCATTTCACCAGAGCCATTCACGTTATCTACGCCGATTCCGATGATGGTTACACTTACCCAGAAAAAAAGATCAAGGGTTACATCACTTCCTTATTTGTTGACCCAATCCCAATGTGA。

[0800] (SEQ ID NO:131)

[0801] MSLNVLSTSGSAPTTKSSEVTRRSANYHPSVWGDKFLEYSSPDHLKNDSDHLKNDAVTEKKHEKLKEEVKKMLVE

[0802] TVQKPQQALNLINEIQRLGLSFHFEPEIEAALRQISVTYHEYCCSTNVDDLHNVALCFRILREHGHKVSCDVFHKFMD

[0803] SNGKLKGSFLNDAIGLLSLYEATHFRVHGEDLLEDLLSLTTSRLEYLKSQMKYPLEDEITRALKHPLHKELNRLGARY

[0804] YISIYEKYDSHNKLLLEFAKLDGNRMQKMYQHELAELTRWWKDLDFTNKLPFARDRIVEGYFLIYGMYFEPECKDV

[0805] REFLNRVFALISHVDDTYDVYGTFEEVILFTHAIERWETSALDQLPEYMKIIYQALMDVYSQMEEKLAKKADCPTYR

[0806] LEFAIETVKALFRSYLEEARWSKERYIPTMEEYMTVALVSVGYKTILTNSFVGMGDTATREVFEWVFSSPLIVRASDLI

[0807] ARLGDDIGGHEEEQKKGDAATAVECYMKEHGVTKQEAYAEFQKQIDNAWKDLNQEALRPFPVPMTYITRVVHFTRAIHVIYADSDDGYTRPEKKIKGYITSLLVDPIPM。

[0808] (SEQ ID NO:132)

[0809] ATGTCTTTGAACGTATTGTCAACTTCTGGTTCCGCTCCAACCACCAAGTCTAGTGAAGTCACCAGAAGATCTGCT

[0810] AACTACCACCCATCCGTCTGGGGTGACAAGTTCTTGGAATACTCCTCTCCAGACCATTTGAAGAACGATTCCGAC

[0811] CACTTGAAGAACGATGCTGTCACTGAAAAGAAGCACGAAAAACTCAAGGAAGAGTTAAGAAGATGTTGGTTG

[0812] AAACCGTTCAAGCCACAACAAGCTTTGAACTTGATCAACGAAATCCAAAGATTAGGTTTGTCTTTCCACTTC

[0813] GAACCAGAAATCGAAGCTGCCTTGAGACAAATCTCTGTTACCTACCATGAATACTGTTGTTCCACCAACGTGGAT

[0814] GACTTACACAACGTTGCTTTGTGTTTCAGAATTTTGCGTGAACACGGTCATAAGGTTTCCTGTGATGTCTTCCAC

[0815] AAGTTCATGGACTCTAACGGTAAATTGAAGGGTTCTTTCTTGAACGACGCTATTGGCTTGCTGAGCTTGTACGAA

[0816] GCTACCCACTTTAGAGGTTCACGGTGAAGATTTGTTGGAAGATCTACTAAGTTTAACCACCTCCAGATTAGAATAC

[0817] TTAAAATCTCAAATGAAATACCCATTAGAGGATGAAATTACTCGTGCTTTGAAGCATCCATTGCACAAGGAATTA

[0818] AACCGTTTGGGTGCTAGATACTACATTTCAATTTACGAAAAGTACGATTCTCACAACAAGTTGTTGGAATTC

[0819] GCTAAGTTGGACGGTAACCGGATGCAAAAGATGTACCAACACGAATTGGCTGAATTGACCCGTTGGTGGAAGGA

[0820] CTTGGATTTCACTAATAAACTGCCTTTCGCCAGAGACAGAATCGTTGAAGGTTACTTCCTTATTTACGGTATGTAT

[0821] TTCGAACCAGAATGCAAGGATGTTAGAGAATTCTTGAATAGAGTCTTCGCTTTGATCTCCCACGTCGATGACACT

[0822] TACGACGTTTATGGTACTTTCGAAGAAGTTATCTTGTTTACCCACGCTATCGAAAGATGGGAAACTTCTGCATTGG

[0823] ACCAATTACCAGAATACATGAAGATCATCTACCAAGCTTTGATGGATGTCTACTCTCAAATGGAAGAGAAGTTGG

[0824] CCAAGAAAGCTGACTGTCCAACTTACAGATTGGAATTTGCCATTGAAACCGTCAAGGCTCTTTTCAGATCCTACT

[0825] TGGAAGAAGCCAGATGGTCTAAAGAAAGATATATTCCTACCATGGAAGAATATATGACTGTTGCCTTGGTTTCTGT

[0826] TGGTTACAAGACCATCTTGACTAACTCTTTCGTCGGTATGGGTGACACTGCTACAAGAGAAGTCTTTGAATGGGT

[0827] TTTCTCTTCCCCATTGATTGTCAGAGCTTCTGACTTGATTGCTAGATTGGGTGATGACATTGGTGGTCACGAAGAA

[0828] GAACAAAAGAAGGGTGATGCTGCTACTGCCGTCGAATGTTACATGAAGGAACACGGTGTTACTAAGCAAGAAG

[0829] CTTACGCTGAATTCCAAAAGCAAATTGACAACGCTTGGAAGGACTTAAACCAAGAAGCCTTAAGACCATTCCCA

[0830] GTTCCAATGACTTACATCACTAGAGTTGTCCATTTCACGAGAGCTATCCACGTTATCTACGCCGATTCCGACGATGGTTACACTCGTCCAGAAAAGAAGATCAAGGGTTACATTACCTCTTTGTTAGTTGACCCAATCCCAATGTGA。

[0831] (SEQ ID NO:135)

[0832] MRKKETERPTADFKPSLWRNKFLKGAKDFKTVDREATAERLEALKEEVRRMITDEEDKPVQGLRLIDEVKRLGVAY

[0833] HFEKEIADALQKLSPEYIESNSPDLATVSLAFRLLRQGGIKISADVFEKFYDDAGRFKSSLINDVQGLLSLYEAAYCAV

[0834] LGESILDEAIAFTTKHLKELVAQDALTPKLQEQINQALARPERQTLPLLEARYFRSFIQKSSDAKYNKTLLNFAILDHNI

[0835] LLELHKEELNELTKWWKELDFSKKLPYARDRLVAIYFFCLGMEAEPQYAFGREIVTRLDTILSHIHDYYFFYGTLEEL

[0836] ELFTEAVQRWESEAISTLPEDMKLIYRELLDAFNEIEESMAKQGRSWLVEYAKEAFQKVVGAYFILAKWASEGYVPTI

[0837] EEYMPIALISNAMQFVITVSFLGMGDFATKEVFEWISSMPKVVKAASIIGLLLDDMQGHEFGQKIGSWASAIECYTKQHGVSKEEAIKAFEEEVANARKQINAELMKKPQVVARPLLGLILNLARAITFIYAEDDGYFHSKLIKDQIASVLGDELPF。 (SEQ ID NO:136)

[0838] ATGAGAAAGAAGGAAACCGAAAGACCAACCGCTGACTTCCAAGCCATCTTTATTGGAGAAACAAGTTCTTGAAGG

[0839] GTGCCAAGGACTTTAAGACTGTTGACCGGGAAGCTACTGCTGAAAGATTGGAAGCTTTGAAGGAGGAAGTCAG

[0840] AAGAATGATTACCGATGAAGAGGACAAGCCAGTTCAAGGTTTGAGATTGATCGATGAAGTAAAGAGATTGGGTG

[0841] TTGCTTACCATTTCGAAAAGGAAATTGCTGATGCTTTGCAAAATTGAGCCCAGAATACATTGAATCTAACTCTC

[0842] CAGACTTGGCCACTGTCTCCTTGGCTTTCAGATTATTGAGACAAGGTGGTATCAAGATTTCTGCTGATGTTTTCGA

[0843] AAAATTCTACGATGATGCCGGTAGATTCAAGTCCAGTTTGATTAATGATGTCCAAGGTTTGCTTTCATTGTACGAA

[0844] GCTGCCTACTGTGCTGTCTTAGGTGAATCCATCTTGGACGAAGCTATTGCCTTCACCCACTAAGCATTGAAGGAG

[0845] TTAGTTGCTCAAGATGCTTTGACTCCAAAGCTACAAGAACAAATCAACCAAGCTCTAGCCAGACCAGAACGTCA

[0846] AACTTTGCCTTGTTGGAAGCAAGATACTTTAGATCCTTCATCCAAGTCTTCTGACGCTAAGTACAACAAGAC

[0847] CCTCTTGAACTTCGCCATCTTGGACCACAACATCCTATTGGAATTGCACAAGGAAGAATTGAACGAACTGACCA

[0848] ATGGTGGAAGGAACTCGATTTCTCCAAGAAGTTGCCATACGCTAGAGACAGATTGGTCGCCATCTATTTCTTCT

[0849] GTTTGGGTATGGAAGCTGAACCACAATACGCTTTTGGTCGTGAAATTGTTACCAGATTAGACACCATCTTGTCTC

[0850] ACATTCACGACTACTACTTCTTTTACGGTACTTTGGAAGAATTGGAATTGTTCACTGAAGCCGTTCAAAGATGGG

[0851] AATCTGAAGCTATCTCTACCCTGCCAGAAGACATGAAAATTAATCTATAGAGAATTGTTGGACGCTTTCAACGAAA

[0852] TCGAAGAATCCATGGCTAAACAAGGTAGATCTTGGTTGGTTGAATATGCTAAAGAAGCTTTCCAAAAGGTTGTTG

[0853] GTGCTTACTTCATTTTGGCTAAGTGGGCTTCCGAAGGTTACGTTCCAACTATTGAAGAATACATGCCAATCGCTTT

[0854] GATTTCCAACGCTATGCAATTCGTTATCACTGTCTCTTTCTTAGGTATGGGTGACTTCGCTACCAAGGAAGTCTTT

[0855] GAATGGATTTCTTCCATGCCAAAGGTCGTCAAGGCTGCTTCCATCATTGGTTTGTTGTTGGATGACATGCAAGGT

[0856] CACGAATTCGGTCAAAAGATCGGCTCCTGGGCTTCTGCCATCGAATGTTACACTAAGCAACACGGTGTCTCTAAA

[0857] GAAGAGGCTATTAAGGCTTTCGAAGAAGAAGTTGCTAACGCCAGAAAGCAAATCAATGCCGAATTGATGAAGA

[0858] AGCCTCAAGTTGTCGCTCGTCCATTGTTGGGTTTGATTTTAAACTTGGCTAGAGCTATCACATTCATCTACGCTGA

[0859] AGATGATGGTTACTTCCACTCTAAGTTGATCAAGGACCAAATTGCTTCTGTCTTGGGAGACGAATTGCCATTCTGA。

[0860] (SEQ ID NO:139)

[0861] MRKKETERPTADFKPSLWRNHFLKGAKDFKTVDREATAERLEALKEEVRRMITDEEDKPVQGLRLIDEVKRLGVAY

[0862] HFEKEIADAIQKLSPEYIESNSPDLATVSLAFRLLRQGGIKISADVFEKFYDDEGRFKSSLINDVQGLLSLYEAAYMAV

[0863] RGESILDEAIAFTTTHLKELVAQDALTPKLAEQINQALARPERQTLPLLEARYFRSFIQSSSDAKYNKTLLNFAILDHNI

[0864] LLELHKEELNELTKWWKELDFSKKLPYARDRLVALYFFDLGMEFEPQYAFGRKIVTRLDTILSHIHDYYFFYGTLEEL

[0865] ELFTEAVQRWESEAISTLPEDMKLIYRELLDAFNEIEESMAKQGRSWLVRYAKEAFQKVVGAYFILAKWASEGYVPTI

[0866] EEYMPIALISNAMQFVITVSFLGMGDFATKEVFEWISSNPKVVKAASVIGLLLDDMQGHEFGQKIGSWASAIECYTK

[0867] QHGVSKEEAIKAFEEEVANARKQINAELMKKPQVVARPLLGTILNLARAITFIYAEDDGYFHSKLIKDQIASVLGDELPF。

[0868] (SEQ ID NO:140)

[0869] ATGAGAAAGAAAGAAACCGAAAGACCAACTGCGGATTTCAAGCCATCTTTGTGGAGAAACCACTTCTTGAAGG

[0870] GTGCTAAGGATTTCAAGACTGTCGACAGAGAAGCCACCGCTGAACGTTTGGAAGCTTTGAAAGAAGAAGTCAG

[0871] AAGAATGATTACTGATGAAGAAGACAAGCCAGTTCAAGGTTTGAGATTGATTGACGAAGTTAAGAGATTAGGTG

[0872] TCGCTTACCATTCGAAAAGGAAATCGCTGACGCTATCCAAAGTTGTCTCCAGAATACATTGAATCCAACTCCC

[0873] CAGACCTAGCTACTGTCTCTTTGGCCTTCCGTTTGTTGAGACAAGGTGGTATCAAGATTTCTGCCGATGTCTTCG

[0874] AAAAGTTCTACGATGACGAAGGTAGATTCAAATCATCCCTTATTAACGATGTTCAAGGTTTGTTATCCTTGTACGA

[0875] AGCTGCTTACATGGCCGTTAGAGGTGAATCTATCCTAGACGAAGCTATAGCTTTTACCACGACTCATTTGAAGGA

[0876] ATTGGTTGCTCAAGATGCTTTGACTCCAAAGTTGGCCGAACAAATCAACCAAGCTTTAGCTCGTCCAGAAAGAC

[0877] AAACTTTACCATTGTTGGAAGCCAGGTATTTCAGATCTTTCATCCAATCCTCCTCTGACGCCAAGTACAACAAGA

[0878] CCTTATTGAACTTCGCCATTTTGGACCACAACATCCTCTTGGAATTGCACAAGGAAGAATTGAATGAATTGACCA

[0879] AGTGGTGGAAGGAATTGGATTTCTCTAAGAAGTTGCCATACGCTCGTGACAGATTAGTTGCTTTGTATTTCTTCG

[0880] ACTTGGGTATGGAATTCGAACCACAATACGCCTTTGGTCGAAAAATTGTCACCAGATTGGACACTATCTTGTCTC

[0881] ACATTCACGACTACTACTTCTTTTACGGTACTTTGGAAGAGTTGGAACTCTTCACAGAAGCTGTCCAAAGATGGG

[0882] AATCTGAAGCTATTTCTACTCTGCCTGAAGACATGAAATTGATTTACAGAGAATTATTGGATGCTTTTAACGAAAT

[0883] TGAAGAATCCATGGCTAAGCAAGGTAGATCCTGGTTGGTGAGATACGCTAAGGAAGCCTTTCAAAAGGTCGTTG

[0884] GTGCCTACTTCATTTTGGCTAAATGGGCTTCCGAAGGTTACGTTCCAACCATCGAAGAATATATGCCAATCGCTTT

[0885] GATCTCTAATGCTATGCAATTCGTCATCACCGTCTCTTTCTTAGGTATGGGTGACTTCGCTACCAAGGAAGTTTTC

[0886] GAATGGATTTCTTCTAACCCAAAGGTTGTCAAGGCTGCTTCTGTCATTGGTCTATTGTTGGATGATATGCAAGGTC

[0887] ACGAATTCGGTCAAAAGATCGGTTCTTGGGCTTCTGCTATCGAATGTTACACTAAGCAACACGGTGTTTCCAAGG

[0888] AAGAAGCTATCAAGGCCTTTGAAGAAGAAGTTGCTAACGCCAGAAAGCAAATCAACGCTGAATTGATGAAGAA

[0889] GCCTCAAGTTGTTGCCAGACCATTGTTGGGTACCATCTTAAACTTGGCTAGAGCTATCACTTTCATCTACGCTGAAGATGACGGTTACTTCCACAGCAAATTAATCAAGGACCAAATTGCTTCCGTTTTGGGCGATGAATTGCCATTCTGA。(SEQ ID NO:143)

[0890] MRKKETERPTADFKPSLWRNHFLKGAKDFKTVDREATAERLEALKEEVRRMITDEEDKPVQGLRLIDEVKRLGVAY

[0891] HFEKEIADAIQKLSPEYIHSNSPDLATVSLAFRLLRQGGIKISADVFEKFYDDEGRFKSSLINDVQGLLSLYEAAYMAV

[0892] RGESILDEAIAFTTTHLKSLVAQDALTPKLAEQINQALARPERQTLPLLEARYFRSFIQSTSDALYNKTLLNFAILDFNIL

[0893] LELHKEELNELTKWWKELDFSKKLPYARDRLVALYFFDLGMEFEPQYAFGRKIVTRLNTILSHIDDYYFFYGTLEELE

[0894] LFTEAVQRWNSEAISTLPEDMKLIYRELLDAFNEIEESMAKQGRSWLVRYAKEAFQKVVGAYFVLAKWASEGYVPTI

[0895] EEYMPIALISNAMQFVITVSFLGMGDFATKEVFEWISSNPKVVKAASVIGLLLDDMQGHEFGQKIGSWASAIECYTK

[0896] QHGVSKEEAIKAFEEEVANARKQINAELMKKPQVVARPLLGTILNLARAITFIYAEDDGYTHSYLIKDQIASVLGDELPF。

[0897] (SEQ ID NO:144)

[0898] ATGAGAAAGAAGGAAACCGAAAGACCAACTGCTGACTTTAAACCATCTTTGTGGAGAAACCACTTCTTGAAGG

[0899] GTGCCAAGGATTTCAAGACTGTCGATCGTGAAGCTACCGCTGAAAGATTGGAAGCTTTGAAAGAAGAAGTCCG

[0900] CAGAATGATTACTGACGAGGAAGACAAGCCAGTTCAAGGTTTGAGATTAATCGACGAAGTTAAGAGATTAGGTG

[0901] TTGCTTACCATTTCGAAAAAGAGATTGCCGACGCTATCCAAAAGCTGTCTCCAGAATACATTCACAGCAACTCCC

[0902] CAGACTTGGCTACTGTTTCTTTGGCTTTCAGATTACTAAGACAAGGTGGTATCAAGATCTCCGCTGATGTCTTCGA

[0903] AAAGTTCTATGATGACGAAGGTAGATTCAAGTCCTCTCTAATTAACGATGTTCAAGGTTTGTTGTCCTTGTACGAA

[0904] GCTGCTTACATGGCTGTTAGAGGCGAATCTATCTTAGACGAAGCCATTGCATTCACCACTACTCATTTGAAGTCTT

[0905] TGGTTGCTCAAGATGCTTTGACTCCAAAGTTGGCTGAACAAATTAACCAAGCTTTGGCAAGACCAGAACGTCAA

[0906] ACTTTGCCATTGTTGGAAGCCCGTTACTTCAGATCTTTCATTCAATCCACCTCTGATGCCTTGTACAACAAGACCT

[0907] TGTTGAACTTCGCCATATTGGACTTCAACATCTTATTGGAATTGCACAAGGAAGAATTGAATGAATTGACCAAGT

[0908] GGTGGAAGGAACTGGACTTCTCTAAGAAACTCCCATACGCCAGAGACAGATTGGTCGCTCTATATTTTTTCGATT

[0909] TGGGTATGGAATTTGAACCACAATACGCCTTCGGTAGAAAGATCGTTACCAGATTGAACACTATCTTGTCTCACAT

[0910] TGACGACTACTACTTCTTCTACGGTACTTTGGAAGAATTAGAATTGTTCACTGAAGCAGTCCAAAGATGGAACTC

[0911] TGAAGCTATCTCTACCTTGCCAGAAGATATGAAATTAATTTACAGAGAATTGTTGGACGCTTTTAACGAAATCGA

[0912] AGAATCCATGGCCAAACAAGGTCGTTCCTGGTTAGTAAGATACGCTAAGGAAGCTTTCCAAAAGGTTGTTGGTG

[0913] CTTACTTCGTTTTGGCTAAATGGGCTAGTGAAGGTTACGTTCCAACCATTGAAGAATATATGCCAATTGCTTTGAT

[0914] TTCAAATGCTATGCAATTCGTCATCACCGTCTCTTTCTTGGGTATGGGTGATTTTGCTACGAAGGAAGTCTTCGAA

[0915] TGGATTTCTTCCAACCCTAAGGTCGTCAAGGCTGCTTCTGTTATCGGTTTGTTATTGGATGACATGCAAGGTCACG

[0916] AATTCGGTCAAAAGATTGGATCCTGGGCTTCTGCTATTGAATGTTACACCAAGCAACACGGTGTCTCCAAGGAG

[0917] GAAGCTATCAAGGCCTTTGAAGAAGAAGTTGCTAACGCCAGAAAGCAAATCAACGCCGAATTGATGAAGAAGC

[0918] CTCAAGTTGTCGCTCGTCCATTATTGGGTACCATCTTGAACTTGGCCAGAGCTATCACTTTCATCTACGCTGAAGACGATGGTTACACTCACTCTTACTTGATCAAGGACCAAATTGCTTCCGTCTTGGGTGACGAACTACCATTCTGA。(SEQ ID NO:147)

[0919] MRKKETFRPTADFKPSLWRNHFLKGAKDFKTVDRTATQERLEALKEEVRRMITDEEDKPVQGLRLIDEVQRLGVAY

[0920] HFEKEIEDAIQKLSPEYIHSNSPDLATVSLAFRLLRQGGIKISADVFEKFYDDEGRFKSSLINDVQGLLSLYEAAYMAV

[0921] RGESILDEAIAFTTTHLKSLVAQDALTPKLAEQINQALARPERQTLPLLEARYFRSFIQSTSDALYNKTLLNFAILDFNIL

[0922] LELHKEELNELTKWWKELDFSKKLPYARDRLVALYFFDLGMEFEPQYAFGRKIVTRLNYILSHIDDYYFFYGTLEELE

[0923] LFTEAVQRWNSEAISTLPEDMKLIYRELLDAFNEIEESMAKQGRSWLVRYAKEAFQKVVGAYFVLAKWASEGYVPTI

[0924] EEYMPIALTSCAMTFVITVSFLGMGDFATKEVFEWISDNPKVVKAASVIGLLLDDMQGHEFGQKIGSVASAIECYTK

[0925] QHGVSKEEAIKAFEEEVANARKQINAELMKKPQVVARPLLGTILNLARAITFIYAEDDGYTHSYLIKDQIASVLGDELPF。

[0926] (SEQ ID NO:148)

[0927] ATGAGAAAGAAAGAAACTTTCAGACCAACTGCTGACTTTAAACCATCCTTATGGAGAAACCACTTCTTGAAGGG

[0928] TGCTAAGGATTTCAAGACTGTTGACAGAACTGCTACTCAAGAAAGATTGGAAGCTTTGAAAGAAGAAGTTAGA

[0929] AGAATGATTACTGATGAAGAAGACAAGCCTGTTCAAGGTTTGAGATTGATTGATGAAGTTCAAAGATTGGGTGT

[0930] CGCTTACCATTTCGAAAAGGAAATCGAAGATGCTATCCAAAAGTTGTCTCCAGAATACATTCACTCCAACTCCCC

[0931] AGACTTGGCCACGTTTCATTGGCTTTCCGTTTGCTAAGACAAGGTGGTATTAAGATCTCTGCTGATGTTTTCGAA

[0932] AAGTTCTACGATGACGAAGGTAGATTCAAATCTTCTTTGATCAACGACGTCCAAGGTTTGTTGAGCTTATACGAA

[0933] GCTGCTTACATGGCTGTTAGAGGTGAATCTATCCTCGACGAAGCTATCGCTTTCACCACCACTCATTTGAAGTCTT

[0934] TAGTTGCTCAAGATGCTCTAACCCCAAAGTTGGCCGAACAAATTAACCAAGCTTTGGCTAGACCAGAAAGACAA

[0935] ACTTTGCCATTGTTAGAAGCCCGTTACTTCAGATCCTTCATTCAGTCCACTTCCGACGCTTTGTACAACAAGACC

[0936] CTGCTTAACTTCGCCATCTTGGATTTCAACATTTTATTGGAATTACACAAGGAAGAATTGAACGAATTGACCAAG

[0937] TGGTGGAAGGAATTGGACTTCTCTAAGAAATTGCCATACGCTCGTGACAGATTGGTTGCCCTCTATTTCTTCGATT

[0938] TGGGTATGGAATTTGAACCACAATACGCGTTTGGTAGAAAGATTGTCACCAGATTGAACTACATCTTGTCTCCACA

[0939] TTGACGACTACTACTTTTTCTACGGTACTTTGGAAGAATTAGAGTTGTTCACTGAAGCTGTCCAAAAGATGGAACT

[0940] CTGAAGCCATCTCTACCTTGCCAGAAAGATATGAAACTAATTTACAGAGAATTATTGGACGCCTTCAATGAAATTG

[0941] AAGAATCCATGGCTAAACAAGGCCGTTCTTGGTTGGTCAGATACGCCAAGGAAGCTTTCCAAAAGGTTGTTGGT

[0942] GCTTATTTCGTTTTGGCTAAGTGGGCTTCTGAAGGTTACGTTCCAACCATCGAAGAATATATGCCAATCGCTCTTA

[0943] CATCATGTGCTATGACTTTCGTCATCACTGTCTCTTTCTTGGGTATGGGTGACTTTGCTACCAAGGAAGTCTTTGA

[0944] ATGGATTAGTGACAACCCAAAGGTCGTCAAGGCCGCCTCTGTTATCGGTTTGTTATTGGACGACATGCAAGGTCA

[0945] CGAATTCGGTCAAAAGATTGGTTCCGTTGCTAGCGCTATTGAATGTTACACCAAGCAACACGGTGTTTCCAAGGA

[0946] AGAAGCAATCAAGGCTTTCGAAGAAGAAGTCGCTAACGCCAGAAAGCAAATCAATGCTGAATTGATGAAGAAG

[0947] CCTCAAGTTGTCGCGCGTCCATTGTTGGGTACCATTTTAAACTTGGCCAGAGCTATTACCTTCATCTACGCTGAAGATGATGGTTACACTCACTCTTACTTGATCAAGGACCAAATCGCTTCTGTCTTGGGTGATGAATTGCCATTCTGA。(SEQ ID NO:151)

[0948] MRSKETFRPTADFKPSLWRNHFLKGAKDFKTVDRTATQERHEALKEEVRRMITDAEDKPVQGLRLIDEVQRLGVAY

[0949] HFEKEIEDAIQKLSPEYIHSNSPDLATVSLAFRLLRQGGIKISADVFEKFYDDEGRFKSSLINDVQGLLSLYEAAYMAV

[0950] RGESILDEAIAFTTTHLKSLVAQDALTPKLAEQINQALARPERQTLPLLEARYFRSFIQSTSDALYNKTLLNFAILDFNIL

[0951] LELHKEELNELTKWWKELDFTKKLPYARDRLVALYFFDLGMEFEPQYAFGRKIVTRLNYILSIIDDYYFFYGTLEELE

[0952] LFTEAVQRWNSEAIDTLPEDMKLIYRELLDAFNEIEEDMAKQGRSHLVRYAKEAFQKVVGAYFVLAKWASEGYVPTI

[0953] EEYMPIALTSCAMTFVITVSFLGMGDFATKEVFEWISDNPKVVKAASVIGLLLDDMQGHEFGQKIGHVASAIECYTK

[0954] QHGVSKEEAIKAFEEEVANARKDINAELMKKPQVVARPLLGTILNLARAITFIYKEDDGYTHSYLIKDQIASVLGDELPF。

[0955] (SEQ ID NO:152)

[0956] ATGAGATCCAAGGAAACTTTCAGACCAACTGCTGATTTTAAGCCATCTTTGTGGAGAAACCACTTCTTGAAGGG

[0957] TGCTAAGGATTTCAAGACTGTTGACAGAACCGCTACTCAAGAAAGACACGAAGCCTTGAAGGAAGAAGTCAGA

[0958] AGAATGATCACTGACGCTGAAGACAAGCCAGTTCAAGGTTTGCGTTTGATTGACGAAGTTCAAAGATTGGGTGT

[0959] CGCTTATCATTTCGAAAAGGAAATCGAAGATGCCATCCAAAAATTGTCCCCAGAATACATTCACTCCAACTCTCC

[0960] AGATTTGGCTACCGTCTCCTTAGCCTTCCGTCTATTGAGGCAGGGTGGTATCAAGATTTCTGCTGACGTTTTCGAA

[0961] AAGTTCTACGATGACGAAGGTAGATTCAAGTCTTCTTTGATCAACGACGTACAAGGTTTGTTATCTTTGTACGAA

[0962] GCTGCTTACATGGCTGTTAGAGGTGAGTCCATCTTAGATGAAGCCATTGCTTTCACCACCACTCATTTGAAGTCCT

[0963] TGGTTGCTCAAGATGCTTTGACTCCAAAGTTGGCTGAACAAATCAACCAAGCTTTGGCACGTCCTGAAAGACAA

[0964] ACTTTGCCATTGTTGGAAGCTAGATATTTCAGATCCTTCATTCAATCAACCTCCGATGCTTTATACAACAAGACCT

[0965] TGTTGAACTTTGCTATTCTAGACTTCAACATCTTGCTGGAATTGCATAAGGAAGAATTAAATGAATTGACTAAGTG

[0966] GTGGAAGGAACTAGATTTCACAAAAAAATTGCCATACGCTAGAGACAGATTAGTTGCTTTATACTTCTTCGATTT

[0967] GGGTATGGAATTCGAACCACAATACGCCTTCGGCAGAAAGATCGTCACCAGATTGAACTACATCTTGTCTATTATC

[0968] GATGACTACTACTTCTTTTACGGTACTTTGGAAGAATTGGAATTGTTCACCGAAGCTGTCCAAAGATGGAACAGC

[0969] GAAGCTATCGACACCTTACCAGAAGACATGAAATTAATTTACAGAGAACTTTTGGACGCCTTCAACGAAATTGA

[0970] AGAAGACATGGCCAAGCAAGGGCGTTCTCACTTGGTGAGATACGCTAAGGAGGCTTTCCAAAAGGTCGTCGGT

[0971] GCTTACTTTGTCTTGGCCAAATGGGCTAGTGAAGGTTACGTTCCAACCATTGAAGAATATATGCCAATTGCTCTAA

[0972] CTTCTTGTGCTATGACTTTCGTTATCACTGTCTCTTCTTGGGTATGGGTGACTTCGCTACGAAGGAAGTCTTCGA

[0973] ATGGATTTCTGACAACCCAAAGGTTGTTAAGGCTGCTTCTGTCATCGGTCTGCTGTTGGATGATATGCAAGGTCA

[0974] CGAATTTGGTCAAGATTGGTCACGTTGCCTCTGCGATAGAATGTTACACTAAGCAACACGGTGTTTCTAAGGA

[0975] AGAAGCCATCAAAGCTTTTGAAGAAGAAGTTGCCAACGCCAGAAAGGACATTAATGCTGAATTGATGAAAAAG

[0976] CCTCAAGTTGTCGCTAGACCACTCTTAGGAACCATCTTGAACTTGGCCAGAGCTATTACCTTCATCTACAAGGAAGACGATGGTTACACCCACTCATACTTGATCAAGGACCAAATCGCTTCCGTTTTGGGTGATGAATTGCCATTCTGA。(SEQ ID NO:155)

[0977] MRSKETFRPTADFKPSLWRNHFLKGASDFKTVDHTATQERHEALKEEVRRMITDAEDKPVQGLRLIDEVQRLGVAY

[0978] HFEKEIEDAIQKLSPNYIHSNSPDLATVSLAFRLLRQGGIKISADVFEKFYDDEGRFKSSLINDVQGLLSLYEAAYMAV

[0979] RGESILDEAIAFTTTHLKSLVAQDALTPKLAEQINHALARPERKTLPLLEARYFRSFIQSTSDHLYNKTLLNFAKLDFNI

[0980] LLELHKEELNELTKWWKELDFTTKLPYARDRLVALYFFDLGMEFEPQYAFGRKIVTRLNYILSIIDDYYFFYGTLEELE

[0981] LFTEAVQRWNSEAIDTLPEDMKLIYRTLLDAFNEIEEDMAKQGRSHLVRYAKEAFQKVVGAYFVLAKWASEGYVPTI

[0982] EEYMPIALTSCAMTFVITVSFLGMGDFATKEVFEWISDNPKVVKAASVIGLLLDDMQGHEFEQKIGHVASAIECYTK

[0983] QHGVSKEEAIKAFEEEVANARKDINEELMKKPQVVARPLLGTILNLARAITFIYKEDDGYTHSYLIKDQIASVLGDELPF。

[0984] (SEQ ID NO:156)

[0985] ATGAGATCTAAAGAAACTTTCCGTCCTACCGCTGACTTCAAGCCATCTTTGTGGAGAAACCATTTCTTGAAGGGT

[0986] GCTTCCGATTTCAAGACCGTTGACCACACTGCTACTCAAGAACGTCACGAAGCTTTGAAGGAAGAAGTTAGAA

[0987] GGATGATTACTGATGCTGAAGACAAGCCAGTTCAAGGTTTGAGATTGATCGATGAAGTCCAACGTTTGGGTGTC

[0988] GCTTACCACTTCGAAAAGGAAATCGAAGACGCTATTCAAAAGTTGTCTCCAAACTATATTCACTCCAACTCCCCA

[0989] GACTTGGCCACCGTCTCATTGGCTTTCAGACTATTAAGACAAGGTGGTATCAAGATTTCTGCTGATGTTTTCGAA

[0990] AAGTTCTACGACGATGAAGGTAGATTCAAGTCTTCTCTAATTAACGATGTCCAAGGTTTATTGTCTTTGTACGAAG

[0991] CTGCTTATATGGCTGTCAGAGGTGAATCCATCTTGGACGAGGCTATTGCTTTCACCACCACTCATCTAAAGTCCTT

[0992] GGTCGCTCAAGATGCTTTGACTCCAAAGTTAGCTGAGCAGATCAACCATGCTTTGGCCAGACCAGAAAGAAAA

[0993] ACCTTGCCATTGTTGGAAGCCCGTTATTTCAGATCCTTCATCCAATCAACCTCTGACCATTTGTACAACAAGACCC

[0994] TGTTGAACTTTGCCAAGTTGGATTTCAACATTTTATTAGAATTGCACAAGGAAGAACTGAATGAATTGACTAAGT

[0995] GGTGGAAGGAATTGGACTTCACTACTAAGTTGCCATACGCTAGAGACAGATTGGTTGCCTTATACTTCTTTGATTT

[0996] GGGTATGGAATTTGAACCACAATACGCCTTCGGTAGAAAGATCGTTACCAGACTGAACTACATCCTCTCTATCATT

[0997] GATGACTACTACTTCTTCTACGGTACCTTGGAAGAATTGGAATTGTTCACTGAAGCTGTTCAAAGATGGAACAGT

[0998] GAAGCAATTGACACCTTGCCAGAAGACATGAAATTAATCTACAGAACTTTACTTGACGCTTTCAACGAAATTGA

[0999] AGAAGATATGGCTAAGCAAGGTCGTTCTCACTTGGTCAGATACGCTAAAGAGGCTTTCCAAAAGGTCGTTGGTG

[1000] CTTACTTCGTCTTGGCAAAATGGGCTTCCGAAGGTTACGTTCCAACTATCGAAGAATACATGCCAATCGCCTTGA

[1001] CATCTTGTGCTATGACCTTCGTCATTACTGTCTCTTTCTTGGGTATGGGTGACTTTGCTACCAAGGAAGTCTTCGA

[1002] ATGGATTAGCGACAACCCAAAGGTTGTCAAGGCTGCCTCTGTTATCGGTTTGTTGTTGGACGACATGCAAGGTC

[1003] ACGAATTCGAACAAAAGATTGGTCACGTTGCCTCCGCCATAGAATGTTTACACCAAGCAACACGGTGTTTCCAAG

[1004] GAAGAAGCTATCAAGGCCTTTGAAGAAGAAAGTTGCTAACGCTAGAAAGGATATCAACGAAGAATTGATGAAAA

[1005] AGCCTCAAGTTGTTGCTAGACCATTGCTTGGTACTATTTTGAATTTGGCTAGAGCTATCACTTTTATCTACAAGGAAGATGATGGTTACACTCACTCTTACTTGATCAAGGATCAAATTGCTTCTGTTTTTGGGCGACGAATTGCCATTCTGA。 (SEQ ID NO:159)

[1006] MRSKETFRPTADFKPSLWRNHFLKGASDFKTVDHTATQERHEALKEEVRRMITDAEDKPVQGLRLIDEVQRLGVAY

[1007] HFEKEIEDAIQKLSPNYIHSNSPDLATVSLAFRLLRQGGIKISADVFEKFYDDEGRFKSSLINDVQGLLSLYEAAYMAV

[1008] RGESILDEAIAFTTTHLKSLVAQDALTKPLAEQINHALARPLRKTLPRLEARYFRSMIQSTSDHLYNKTLLNFAKLDFN

[1009] ILLELHKEELNELTKWWKELDFTTKLPYARDRLVALYFFDLGMEFEPQYAFGRKIMTQLNYILSIIDDYYFFYGTLEEL

[1010] ELFTEAVQRWNIEAVDTLPEYMKLIYRTLLDAFNEIEEDMAKQGRSHLVRYAKEAFQKVVGAYFVLAKWASEGYVP

[1011] TIEEYMPIALTSCAMTFVITVSFLGMGDFATKEVFEWISDNPKVVKAASVIGLLLDDMQGHEFEQKRGHVASAIECYT

[1012] KQHGVSKEEAIKAFEEEVANARKDINEELMMKPQVVARPLLGTILNLARAITFIYKEDDGYTHSYLIKDQIASVLGDEVPF。

[1013] (SEQ ID NO:160)

[1014] ATGAGATCTAAGGAAACTTTCAGACCAACTGCTGATTTCAAGCCATCTTTGTGGAGAAACCACTTCTTGAAGGG

[1015] TGCCAGTGATTTCAAGACTGTTGACCACACTGCTACCCAAGAAAGACACGAAGCTTTGAAGGAAGAAGTCAGA

[1016] AGAATGATTACTGATGCTGAAGACAAGCCAGTTCAAGGTTTGAGATTAATCGACGAAGTTCAAAGATTGGGTGT

[1017] TGCCTATCATTTCGAAAAGGAAATTGAAGACGCCATTCAAAAATTATCCCCAAACTACATCCACTCCAACTCTCC

[1018] AGACTTGGCCACCGTTAGCTTGGCTTTCCGGTTATTAAGACAAGGTGGTATCAAGATCTCTGCTGACGTCTTCGA

[1019] AAAGTTCTACGACGATGAAGGTCGTTTCAAGTCCTCATTGATTAACGATGTCCAAGGTTTGTTGTCTTTGTACGA

[1020] AGCTGCTTACATGGCTGTTAGAGGTGAATCTATTTTGGATGAAGCCATTGCTTTCACCACCACTCACTTGAAGTCT

[1021] CTAGTGGCTCAAGATGCATTGACCCCAAAGTTGGCTGAACAAATCAACCATGCTTTGGCCAGACCATTGCGTAA

[1022] GACCTTGCCAAGATTGGAAGCTCGTTATTTCAGATCCATGATCCAATCTACTTCCGACCACTTATACAACAAGAC

[1023] ACTATTGAACTTCGCTAAGTTGGACTTCAATATTTTGCTAGAATTGCACAAGGAAGAATTGAATGAACTCACCAA

[1024] ATGGTGGAAGGAATTGGACTTTACCACCAAGCTACCATACGCTAGAGACAGATTGGTTGCTTTGTACTTCTTCGA

[1025] TTTGGGCATGGAATTCGAGCCACAATACGCCTTCGGTAGAAAGATCATGACTCAATTGAACTACATTTTGTCCATC

[1026] ATCGATGACTACTACTTCTTTTACGGTACTTTGGAAGAATTGGAATTGTTCACTGAAGCTGTCCAAAGATGGAAC

[1027] ATCGAAGCTGTCGACACTTTGCCAGAATATATGAAATTGATTTACAGAACTTTATTGGATGCTTTCAACGAAATCG

[1028] AAGAAGATATGGCCAAACAAGGTCGTTCCCATTTGGTCAGATACGCTAAGGAAGCTTTCCAAAAGGTCGTTGGT

[1029] GCTTACTTCGTCTTGGCCAAGTGGGCTTCTGAAGGTTACGTTCCAACCATTGAAGAATACATGCCAATCGCTCTA

[1030] ACCTCTTGTGCTATGACCTTCGTTATCACTGTCTCTTTCTTAGGTATGGGTGATTTTGCTACTAAAGAAGTTTTCGA

[1031] ATGGATTTCTGACAACCCAAAGGTTGTTAAGGCCGCTTCTGTCATTGGTTTGTTGTTGGATGACATGCAAGGTCA

[1032] CGAATTTGAACAAAAGAGAGGTCACGTTGCCTCCGCTATTGAATGTTACACCAAGCAACACGGTGTCTCCAAGG

[1033] AAGAAGCTATTAAAGCTTTTGAAGAAGAAGTTGCTAACGCTCGTAAAGACATCAACGAAGAATTGATGATGAAG

[1034] CCTCAAGTTGTCGCCAGACCTCTGTTGGGTACCATCTTGAACTTGGCTAGAGCTATCACTTTCATCTACAAGGAAGATGACGGTTACACCCACTCTTACTTGATCAAGGACCAAATAGCTTCTGTTTTGGGTGACGAAGTCCCATTCTGA。(SEQ ID NO:163)

[1035] MRSKETFRPTADFHPSLWRNHFLKGASDFKTVDHTATQERHEALKEEVRRMITDAEDKPVQKLRLIDEVQRLGVAY

[1036] HFEKEIEDAIQKLSPNYIHSNSPDLATVSLAFRLLRQGGIKISADVFEKFYDDEGRFKSSLINDVQGLLSLYEAAYMAV

[1037] RGEHILDEAIAFTTTHLKSLVAQDAVTPKLAEQINHALYRPLRKTLPRLEARYFRSMIQSTSDHLYNKTLLNFAKLDFN

[1038] ILLELHKEELNELTKWWKELDFTTKLPYARDRLVALYFWDLGMEFEPQYAFGRKIMTQLNYILSIIDDTYFFYGTLEE

[1039] LSLFTEAVQRWNIEAVDTLPEYMKLIYRTLLDAFNEIEEDMAKQGRSHLVRYAKEAFQKVVGAYFVLAKWASEGYV

[1040] PTIEEYMPIALTSCAMTFVITVSFLGMGDFATKEVFEWISDNPKVVKAASVICLLLDDMQGHEFEQKRGHVASAIECY

[1041] TKQHGVSKEEAIKMFEEEVANARKDINEELMMKPQVVARPLLGTILNLARAIDFIYKEDDGYTHSYLIKDQIASVLGDEVPF。

[1042] (SEQ ID NO:164)

[1043] ATGAGATCAAAGGAAACTTTCCGTCCAACCGCTGACTTCCACCCATCTTTGTGGAGAAACCATTTCTTGAAAGG

[1044] TGCATCTGATTTCAAGACTGTTGACCACACTGCTACTCAAGAAAGACACGAAGCTTTAAAGGAAGAAGTCAGA

[1045] AGAATGATCACTGACGCTGAAGACAAGCCAGTTCAAAAGTTGAGATTGATCGATGAAGTCCAAAGATTAGGTGT

[1046] TGCCTACCACTTCGAAAAGGAAATCGAAGATGCTATCCAGAAATTGTCTCCAAACTATATTCACAGCAACTCTCC

[1047] AGACTTGGCCACCGTCTCCTTGGCTTTCAGACTGTTGAGACAAGGTGGTATCAAGATTTCTGCTGATGTCTTCGA

[1048] AAAGTTCTACGATGACGAAGGTAGATTCAAGTCTTCTTTGATCAACGATGTTCAAGGTTTGCTCTCTTTGTACGA

[1049] AGCTGCCTATATGGCTGTTCGTGGTGAACACATTCTAGATGAAGCCATTGCTTTCACCACAACCCATTTGAAGTC

[1050] CCTCGTTGCTCAAGATGCTGTCACTCCAAAGTTGGCTGAACAAATCAACCACGCTTTTATACCGTCCCTCTTAGAAA

[1051] GACCTTACCTAGATTAAGCGCGTTATTTCAGATCCATGATTCAATCTACCTCCGATCATCTCTACAACAAGACC

[1052] TTGTTGAACTTCGCTAAGTTGGACTTCAACATTTTGTTGGAATTGCACAAGGAAGAGTTGAACGAATTGACTAAA

[1053] TGGTGGAAGGAACTTGACTTCCACCACCAAGCTGCCATACGCCAGAGACAGATTGGTCGCCCTTTACTTCTGGGA

[1054] CTTGGGTATGGAATTCGAACCACAATACGCTTTCGGTAGAAAGATCATGACCCAATTGAACTACATCCTAAGTATC

[1055] ATCGATGACACTTACTTCTTCTACGGTACTTTGGAAGAGTTATCCTTGTTCACTGAAGCCGTCCAAAGATGGAAC

[1056] ATCGAAGCTGTTGATACGTTGCCAGAATACATGAAATTGATTTACAGAACTTTGTTGGACGCTTTCAACGAAATT

[1057] GAAGAAGACATGGCCAAGCAAGGTAGATCTCACTTGGTTAGATACGCTAAGGAAGCCTTCCAAAAGGTTGTTTGG

[1058] TGCTTACTTTGTCTTGGCCAAGTGGGCATCTGAAGGTTACGTTCCAACTATTGAAGAATACATGCCAATCGCTTTG

[1059] ACTTCTTGTGCTATGACCTTTGTTATTACTGTCTCTTTCTTGGGTATGGGTGACTTTGCTACCAAGGAAGTTTTTGA

[1060] ATGGATCTCTGACAACCCAAAGGTCGTCAAGGCTGCTTCCGTGATCTGTTTGCTATTAGATGATATGCAAGGTCA

[1061] CGAATTTGAACAAGAGAGGTCATGTCGCTTCCGCCATCGAATGTTACACCAAGCAACACGGTGTCTCCAAGG

[1062] AAGAAGCTATCAAGATGTTCCAAGAAGAAGTTGCTAACGCTAGAAAGGACATTAATGAAGAATTGATGATGAAA

[1063] CCACAAGTTGTTGCTCGTCCATTGTTGGGCACCATTTTGAATTTAGCTAGAGCTATTGACTTCATTTACAAGGAAGATGACGGTTACACTCACTCTTACTTGATCAAGGATCAAATTGCCTCCGTTTTGGGTGACGAAGTCCCATTCTGA。(SEQ ID NO:167)

[1064] MSSKETFRPTADFHPSLWRNHFLKGASDFKTVDHTATQERHEALKEEVRRMITDAEDKPVQKLRLIDEVQRLGVAY

[1065] HFEKEIEDAIQKLSPNYIHSNSPDLATVSLAFRLLRQGGIKISCDVFEKFKDDEGRFKSSLINDVQGLLSLYEAAYMAV

[1066] RGEHILDEAIAFTTTHLKSLVAQDAVTPKLAEQINHALYRPLRKTLPRLEARYFMSMINSTSDHLYNKTLLNFAKLDF

[1067] NILLELHKEELNELTKWWKELDFTTKLPYARDRLVALYFWDLGTEFEPQYAFGRKIMTQLNYILSIIDDTYDAYGTLE

[1068] ELSLFTEAVQRWNIEAVDTLPEYMKLIYRTLLDAFNEIEEDMAKQGRSHLVRYAKEAFQKVIGAYFVLAKWFSEGYV

[1069] PTIEEYMPIALTSCAMTFVITVSFLGMGDFATKEVFEWISDNPKVVKAASVICLLLDDMQGHEFEQKRGHVASAIECY

[1070] TKQHGVSKEEAIKMFEEEVANAWKDINEELMMKPQVVARPLLGTILNLARAIDFIYKEDDGYTHSYLIKDQIASVLGDEVPF。

[1071] (SEQ ID NO:168)

[1072] ATGTCTTCCAAGGAAACCTTCAGACCAACTGCTGATTTCCACCCATCTTTGTGGAGAAACCATTTCTTAAAGGGT

[1073] GCTTCCGATTTCAAGACTGTTGACCACACTGCCACCCAAGAAAGACACGAAGCTTTGAAGGAAGAAGTTAGAA

[1074] GAATGATCACTGATGCTGAAGACAAGCCTGTTCAAAAGTTACGTTTGATTGACGAAGTCCAAAGACTAGGTGTT

[1075] GCTTACCACTTCGAAAAGGAAATTGAAGACGCTATCCAAAAATTGAGTCCAAACTACATTCACTCCAACTCACC

[1076] AGACTTGGCTACTGTTTCTTTGGCCTTCAGATTATTGAGACAAGGTGGTATCAAGATCTCTTGTGATGTTTTCGAA

[1077] AAGTTCAAGGATGACGAAGGTAGATTCAAATCTTCTTTGATTAACGATGTCCAAGGCTTGCTGTCCTTTATACGAA

[1078] GCCGCTTACATGGCTGTCCGTGGTGAACACATCTTGGACGAAGCTATTGCTTTCACCACCACCCACTTGAAGTCC

[1079] TTAGTGGCTCAAGATGCCGTTACTCCAAAGTTGGCTGAACAAATCAACCACGCTTTGTACAGACCATTGAGAAA

[1080] GACCTTGCCAAGATTGGAAGCTCGTTACTTCATGTCCATGATTAACTCCACTTCTGACCATTTGTACAACAAGAC

[1081] ACTACTCAACTTCGCTAAGTTGGATTTCAACATCTTTGTTGGAATTGCACAAGGAAGAATTGAACGAATTGACCAA

[1082] ATGGTGGAAGGAATTAGACTTCACCACTAAGTTGCCATACGCCAGAGACAGATTGGTCGCATTGTATTCTGGGA

[1083] TTTGGGTACCGAATTTGAGCCCAATACGCTTTCGGTCGTAAAATCATGACTCAATTGAACTACATTTTGTCTATC

[1084] ATAGACGATACATACGACGCTTACGGTACTTTGGAAGAACTTTCTTTGTTCACTGAAGCTGTTCAAAGATGGAAC

[1085] ATTGAAGCTGTCGACACCCTACCAGAATACATGAAGTTAATTTACAGAACTTTGCTAGACGCCTTTTAATGAAATC

[1086] GAAGAAGATATGGCCAAGCAAGGTAGATCTCATTTGGTTAGATACGCCAAAGAAGCCTTCCAGAAGGTCCATCGG

[1087] TGCCTATTTCGTCTTGGCTAAGTGGTTCTCTGAAGGTTACGTTCCAACCATTGAAGAATATGCCAATTGCTTTG

[1088] ACTTCCTGCGCTATGACTTTTGTTATCACCGTATCATTCTTGGGTATGGGTGACTTTGCTACCAAGGAAGTTTTTG

[1089] AATGGATTTCCGACAACCAAAGGTCGTCAAGGCTGCCTCCGTTATCTGTTGTTGTTGGACGACATGCAAGGTC

[1090] ACGAATTCGAACAAAAGAGAGGTCATGTTGCTTCTGCTATTGAATGTTACACAAGCAACACGGTGTCTCTAAG

[1091] GAAGAAGCTATCAAGATGTTCGAAGAAGTAAGTCGCTAACGCTTGGAAGGACCATCAATGAAGAATTGATGATGAA

[1092] ACCTCAAGTTGTTGCTAGACCATTGTTAGGTACCATTTTGAACTTGGCCAGAGCTATTGATTTCATCTACAAGGAAGATGATGGTTACACTCACTCTACTTGATCAAGGACCAAATCGCGTCTGTTTTGGGTGAATGAAGTCCCATTTTGA。 (SEQ ID NO:171)

[1093] MSSKETFRPTADFHPSLWRNHFLKGASDFKTVDHTATQERHEALKEEVRRMITDAEDKPVQKLRLIDEVQRLGVAY

[1094] HFEKEIEDAIQKLCPNYIHSNSPDLHTVSLAFRLLRQGGIKISCDVFEKFKDDEGRFKSSLINDVQGLLSLYEAAYMAV

[1095] RGEHILDEAIAFTTTHLKSLVAQDHVTKPLAEQINHALYRPLRKTLRLEARYFMSMINSTSDHLYNKTLLNFAKLDF

[1096] NILLELHKEELNELTKWWKELDFTTKLPYARDRLVELYFWDLGTYFEPQYAFGRKIMTQLNYILSIIDDTYDAYGTLE

[1097] ELSLFTEAVQRWNIEAVDTLPEYMKLIYRTLLDAFNEIEEDMAKQGRSHCVRYAKEAFQKVIGAYFVQAKWFSEGY

[1098] VPTIEEYMPIALTSCAYTFVITNSFLGMGDFATKEVFEWISDNPKVVKAASVICLLLDDMQGHEFEQKRGHVASAIEC

[1099] YTKQHGVSKEEAIKMFEEEVANAWKDINEELMMKPTVVARPLLGTILNLARAIDFIYKEDDGYTHSYLIKDQIASVLGDHVPF。

[1100] (SEQ ID NO:172)

[1101] ATGTCTTCCAAGGAAACTTTCAGACCAACTGCTGACTTCCACCCATCTTTGTGGAGAAATCATTTCTTGAAGGGT

[1102] GCTTCTGACTTCAAAACTGTCGATCACACCGCCACCCAAGAAAGACACGAAGCTTTGAAAGAAGAAGTCAGAA

[1103] GAATGATCACTGATGCTGAAGACAAGCCTGTCCAAAAATTGAGATTGATTGATGAAGTCCAAAGACTAGGTGTT

[1104] GCTTACCACTTCGAAAAGGAAATCGAGGATGCTATCCAAAAGTTGTGTCCAAACTACATTCACTCCAACTCTCCA

[1105] GATTTGCACACTGTTTCCTTGGCTTTCAGATTATTGAGACAAGGTGGTATTAAGATTTCATGTGATGTCTTTGAAA

[1106] AGTTCAAGGATGATGAAGGTAGATTCAAGTCTTCTTTGATCAACGATGTCCAAGGTTTGTTGTCCCTATACGAAG

[1107] CCGCTTATATGGCTGTCAGAGGTGAACACATTTTGGACGAAGCTATTGCTTTCACTACCACTCACTTGAAGAGCC

[1108] TAGTCGCTCAAGATCATGTCACTCCAAAGTTGGCTGAACAAATCAACCACGCTTTGTACAGACCTCTTAGAAAG

[1109] ACCTTACCAAGATTGGAAGCTCGTTATTTCATGTCCATGATTAATTCTACCTCCGACCATTTGTACAACAAGACTC

[1110] TCTTGAACTTCGCTAAGTTGGATTTCAACATTTTGTTGGAATTGCACAAGGAAGAATTAAACGAATTGACCAAAT

[1111] GGTGGAAAGAACTAGATTTCACCACCAAGTTGCCATACGCTAGAGACAGATTGGTTGAATTATACTTCTGGGACT

[1112] TGGGCACCTACTTTGAACCACAATACGCCTTCGGTCGGAAGATCATGACTCAATTGAACTATATCTTGTCCATCAT

[1113] CGATGACACTTACGACGCTTACGGTACTCTGGAAGAATTGTCTTTATTCACTGAAGCTGTCCAAAGATGGAACAT

[1114] CGAAGCTGTTGACACCTTGCCAGAATACATGAAATTAATTTACCGTACTTTGTTGGACGCATTTAATGAAATTGAA

[1115] GAAGACATGGCCAAGCAAGGTCGTAGTCATTGCGTTAGATACGCTAAGGAAGCTTTCCAAAAGGTTATTGGTGC

[1116] TTACTTCGTTCAGGCTAAGTGGTTCTCTGAAGGTTACGTTCCAACCATTGAAGAATACATGCCAATCGCCTTGAC

[1117] TTCTTGTGCTTACACCTTTGTGATCACCAACTCTTTCTTGGGTATGGGTGACTTTGCTACCAAGGAAGTTTTCGAA

[1118] TGGATTTCCGACAACCCAAAGGTCGTCAAGGCTGCCTCCGTTATCTGTTTGTTATTGGACGACATGCAAGGTCAC

[1119] GAATTCGAACAAAAAAGAGAGGTCACGTTGCCTCTGCTATCGAATGTTACACTAAACAACACGGTGTCTCTAAGGA

[1120] AGAAGCCATCAAGATGTTCGAAGAAGAAGTTGCTAACGCTTGGAAGGACATCAACGAAGAATTGATGAAG

[1121] CCAACAGTTGTTGCCAGACCATGTTAGGTACTATCTTGAACTTGGCGCGTGCCATTGACTTCATCTACAAGGAAGATGACGGTTACACCCACTCTTACTTGATTAAGGACCAAATAGCTTCTGTTTTGGGTGATCATGTTCCATCTGA。

[1122]

[1123]

Claims

1. Valencene synthase, characterized in that The valencene synthase comprises domains with Pfam numbers of PF01397 and PF03936 and has valencene synthase activity. The valencene synthase is derived from Cimicifuga racemosa ( Actaea racemosa ), wherein the valencene synthase comprises the amino acid sequence shown in SEQ ID NO:

2.

2. A nucleic acid molecule, characterized in that The nucleic acid molecule comprises a nucleotide sequence encoding the valencene synthase of claim 1 or a nucleotide sequence complementary to its base.

3. The nucleic acid molecule according to claim 2, characterized in that The nucleotide sequence of the nucleic acid molecule is shown in SEQ ID NO:

5.

4. A recombinant expression vector containing the nucleic acid molecule according to claim 2 or 3, characterized in that: The original vector of the recombinant expression vector is pZY900, pYR017 or pYR018.

5. A transformant containing the nucleic acid molecule according to claim 2 or 3, or containing the recombinant expression vector according to claim 4, wherein the host cell of the transformant is selected from a fungal expression system.

6. The transformant according to claim 5, wherein The fungal expression system is a yeast expression system.

7. The transformant according to claim 6, wherein The yeast expression system is a Saccharomyces cerevisiae expression system.

8. Recombinant Saccharomyces cerevisiae, characterized in that The recombinant Saccharomyces cerevisiae contains the nucleic acid molecule according to claim 2 or 3, or contains the recombinant expression vector according to claim 4.

9. The recombinant Saccharomyces cerevisiae according to claim 8, wherein The original vector of the recombinant expression vector is pZY900, pYR017 or pYR018.

10. A method for preparing a flavor composition, characterized in that: The preparation method comprises fermenting and culturing the transformant according to any one of claims 5 to 7 or the recombinant Saccharomyces cerevisiae according to claim 8 or 9, and recovering the flavor composition from the fermentation product.

11. The preparation method according to claim 10, characterized in that: The recovery method includes extracting the fermentation product using an oil phase.

12. The preparation method according to claim 11, characterized in that: The oil phase includes at least one of isopropyl myristate or n-dodecane.

13. The preparation method according to claim 11, characterized in that: The recovery method is to add the oil phase during the fermentation process, collect the oil phase after the fermentation is completed, and separate and obtain the flavor composition enriched in the oil phase.

14. The preparation method according to claim 13, characterized in that: The method of collecting the oil phase includes centrifugation.

15. The preparation method according to claim 13, characterized in that: The separation method includes distillation.

16. Use of a valencene synthase comprising the amino acid sequence of SEQ ID NO: 1 in an expression system for catalyzing valencene synthesis, wherein the valencene synthase comprises domains with Pfam numbers PF01397 and PF03936 and has valencene synthase activity, and the valencene synthase is derived from Cimicifuga racemosa ( Actaea racemosa ).

17. A method for preparing a flavor composition, characterized in that: The preparation method comprises fermenting and culturing a transformant containing a nucleic acid molecule or a recombinant expression vector or a recombinant saccharomyces cerevisiae containing a nucleic acid molecule or a recombinant expression vector, and recovering the flavor composition from the fermentation product; Wherein, the nucleic acid molecule comprises a nucleotide encoding the valencene synthase for use according to claim 16 or a nucleotide sequence complementary to its base; The recombinant expression vector contains the aforementioned nucleic acid molecule, and the original vector of the recombinant expression vector is pZY900, pYR017 or pYR018.

18. The preparation method according to claim 17, characterized in that: The recovery method includes extracting the fermentation product using an oil phase.

19. The preparation method according to claim 18, characterized in that: The oil phase includes at least one of isopropyl myristate or n-dodecane.

20. The preparation method according to claim 18, characterized in that: The recovery method is to add the oil phase during the fermentation process, collect the oil phase after the fermentation is completed, and separate and obtain the flavor composition enriched in the oil phase.

21. The preparation method according to claim 20, characterized in that: The method of collecting the oil phase includes centrifugation.

22. The preparation method according to claim 20, characterized in that: The separation method includes distillation.

Images