CN106715689B - 裂解酶以及不对称合成(s)-苯基乙酰基甲醇的方法 - Google Patents

裂解酶以及不对称合成(s)-苯基乙酰基甲醇的方法 Download PDF

Info

Publication number
CN106715689B
CN106715689B CN201580049895.0A CN201580049895A CN106715689B CN 106715689 B CN106715689 B CN 106715689B CN 201580049895 A CN201580049895 A CN 201580049895A CN 106715689 B CN106715689 B CN 106715689B
Authority
CN
China
Prior art keywords
ala
leu
gly
val
thr
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201580049895.0A
Other languages
English (en)
Other versions
CN106715689A (zh
Inventor
D.罗瑟
M.波尔
T.塞尔
L.马克斯
R.韦斯特法尔
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Forschungszentrum Juelich GmbH
Original Assignee
Forschungszentrum Juelich GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Forschungszentrum Juelich GmbH filed Critical Forschungszentrum Juelich GmbH
Publication of CN106715689A publication Critical patent/CN106715689A/zh
Application granted granted Critical
Publication of CN106715689B publication Critical patent/CN106715689B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/24—Preparation of oxygen-containing organic compounds containing a carbonyl group
    • C12P7/26—Ketones
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/88—Lyases (4.)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y401/00—Carbon-carbon lyases (4.1)
    • C12Y401/01—Carboxy-lyases (4.1.1)
    • C12Y401/01001—Pyruvate decarboxylase (4.1.1.1)

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

本发明涉及裂解酶以及用于不对称合成(S)‑苯基乙酰基甲醇的方法。根据本发明提供裂解酶，其中在相对于巴氏醋杆菌野生型修饰的蛋白ApPDC‑E469G中在位置号468中的异亮氨酸被比异亮氨酸较不占空间的氨基酸置换。在一个有利的实施方案中，本发明的酶在位置号543中的氨基酸色氨酸被比色氨酸较小占据空间的其它氨基酸替换。本发明的酶可用于不对称合成(S)‑苯基乙酰基甲醇。在此可以实现最高98%ee的对映体过量。

Description

裂解酶以及不对称合成(S)-苯基乙酰基甲醇的方法
本发明涉及裂解酶以及不对称合成(S)-苯基乙酰基甲醇的方法。
(S)-苯基乙酰基甲醇是有机合成中有价值的手性单元并且可用于合成精细化学品和药物。根据迄今的现有技术，并不已知能够借助不对称合成由非手性的廉价化合物以>89 % ee的光学纯度生成(S)-苯基乙酰基甲醇(S)-PAC的方法。但是，在制备精细化学品或药物时，高的光学纯度是极其重要的。
根据现有技术已知制备(S)-苯基乙酰基甲醇的各种方法。
一方面，已知化学合成。
基于化学不对称合成的(S)-PAC制备方法生成68 %或86%的ee。这些方法描述在出版物Davis, Franklin A.; Sheppard, Aurelia C.; Lal, G. Sankar TetrahedronLetters, 1989, 第30卷, 7 第779 - 782页和Adam, Waldemar; Fell, Rainer T.;Stegmann, Veit R.; Saha-Moeller, Chantu R. Journal of the American ChemicalSociety, 1998, 第120卷, 4 第708 - 714页中。此外，还有仅作为副产物产生(S)-PAC且(R)-PAC以对映体过量形式存在的方法，这例如通过下列反应，例如描述在出版物Toukoniitty, Esa; Maeki-Arvela, Paeivi; Kuzma, Marek; Villela, Alexandre;Kalantar Neyestanaki, Ahmad; Salmi, Tapio; Sjoeholm, Rainer; Leino, Reko;Laine, Ensio; Murzin, Dmitry Yu, Journal of Catalysis, 2001, 第204卷, 2 第281- 291页中的1-苯基丙-1,2-二酮的还原和描述在Fleming, Steven A.; Carroll, SeanM.; Hirschi, Jennifer; Liu, Renmao; Pace, J. Lee; Redd, J. Ty TetrahedronLetters, 2004, 第45卷, 17 第3341 - 3343页中的由苯甲醛起始的合成和描述在Brussee, J.; Roos, E. C.; Gen, A. Van Der Tetrahedron Letters, 1988 , 第29卷,35 第4485 - 4488页中的2-羟基-2-苯基乙腈的反应。
此外，描述了手性单元1-苯基丙-1,2-二醇可以氧化成(S)-PAC的合成。(S)-PAC以91 %的对映体过量产生，如由Zi-Qiang Rong, Hui-Jie Pan, Hai-Long Yan和Yu ZhaoOrganic Letters, 2014, 16 (1), 第208–211页描述，或69 %的对映体过量，如由Waldemar Adam, Chantu R. Saha-Moeller和Cong-Gui Zhao Journal of OrganicChemistry, 64(20), 7492-7497; 1999描述，但是此外被必须复杂分离出的区域异构体污染。
此外，已知描述在Álvaro Gómez Baraibar于2013年的题为“Development of abiocatalytic production process for (S)-alpha-hydroxy ketones”博士论文中的酶促不对称合成。如果将根据该博士论文的这种在大肠杆菌中异源表达的酶用于在全细胞中合成，(S)-PAC的光学纯度为~43 % ee。
(S)-PAC的这个唯一的酶促不对称合成描述在由苯甲醛和乙醛或苯甲醛和丙酮酸起始的碳连接反应中。该反应由酶，即来自巴氏醋杆菌的丙酮酸脱羧酶的变体ApPDC-E469G催化，其中在位置号469中的谷氨酸被甘氨酸替换。在此通过分离的酶实现的最高对映体过量为89%，如由出版物Rother Nee Gocke, Doerte; Kolter, Geraldine; Gerhards,Tina; Berthold, Catrine L.; Gauchenova, Ekaterina; Knoll, Michael; Pleiss,Juergen; Mueller, Michael; Schneider, Gunter; Pohl, Martina, ChemCatChem,2011, 第3卷, 10 第1587 - 1596页描述。
由现有技术出发，本发明的目的是提供不对称合成(S)-苯基乙酰基甲醇的替代性酶促方法，其实现(S)-苯基乙酰基甲醇的高对映体过量。在用全细胞制备时，对映体过量应大于43%。
此外，不应形成副产物和区域异构体。在此，应能够使用非手性的廉价反应物。应实现(S)-苯基乙酰基甲醇的不对称合成。应防止手性产物混合物的昂贵分离。
应提供可以用于由苯甲醛和丙酮酸或乙醛制备(S)-苯基乙酰基甲醇的酶，以及编码该酶的DNA。
此外应提供制备该酶的方法。应克服现有技术中存在的缺点和问题。
应提供制备(S)-苯基乙酰基甲醇的方法，其甚至在使用粗细胞提取物（Rohzellextrakt）或全细胞时实现高对映体过量。应累积地克服现有技术的缺点。
由权利要求1的上位概念和从属权利要求出发，所述目的根据本发明通过在权利要求的特征部分中给出的特征来实现。该目的根据本发明通过裂解酶ApPDC-E469G的变体来实现，在该变体的位置号468中的异亮氨酸被具有相对于异亮氨酸减小的占据空间的氨基酸替换。此外，通过根据从属权利要求将裂解酶用于使苯甲醛与丙酮酸或乙醛反应成(S)-苯基乙酰基甲醇，实现该目的。
通过本发明的裂解酶以及(S)-苯基乙酰基甲醇的制备方法，现在可以在使用全细胞时以93% ee和在使用粗细胞提取物时以85% ee制备(S)-苯基乙酰基甲醇。不形成副产物，特别是不产生区域异构体。由于该合成用非手性反应物也可实现，其是廉价的。可以免除对映体的分离。在制备(S)-苯基乙酰基甲醇时，也可以通过粗细胞提取物或全细胞实现高对映体过量。累积地消除根据现有技术描述的所有缺点。
本发明的有利的扩展实施方案在从属权利要求中给出。
根据本发明提供裂解酶，其中在相对于巴氏醋杆菌野生型修饰的蛋白ApPDC-E469G中在位置号468中的异亮氨酸被比异亮氨酸较不占空间的氨基酸置换。
该裂解酶对于在制备(S)-苯基乙酰基甲醇时提高立体选择性而言具有有利影响。
优选地，可以提及满足这些要求的下列裂解酶：
- 根据序列号1在位置号468中具有甘氨酸的ApPDC-E469G-I468G
- 根据序列号2在位置号468中具有丙氨酸的ApPDC-E469G-I468A
- 根据序列号3在位置号468中具有缬氨酸的ApPDC-E469G-I468V。
为了改进对映体过量，也可以在制备(S)-苯基乙酰基甲醇时使用酶ApPDC-E469G-I468L、ApPDC-E469G-I468T、ApPDC-E469G-I468C或ApPDC-E469G-I468S。
此外，提供编码所述酶的本发明的脱氧核糖核酸。
根据本发明，这是编码酶ApPDC-E469G的变体的脱氧核糖核酸，其在位置号1402至1404中编码相对于异亮氨酸具有减小的占据空间的氨基酸。
对于在所述位置中编码氨基酸甘氨酸的根据序列号1的实例，可以在位置号1402-1404中例如存在核酸GGT。
例如，描述了根据序列号4的编码根据序列号1的在位置号 468中具有甘氨酸的酶ApPDC-E469G-I468G的脱氧核糖核酸。
对于本发明的根据序列号2的在位置号468中具有丙氨酸的酶ApPDC-E469G-I468A和根据序列号3的在位置号468中具有缬氨酸的酶ApPDC-E469G-I468V，可以通过替换位置号1402-1404中的相应核苷酸提供编码其的脱氧核糖核酸。
编码本发明的酶的DNA可以根据本领域技术人员已知的方法通过定向或不定向的诱变来产生。在此，优选的是定向诱变。这些方法是本领域技术人员已知的。在具体的描述部分中，具体公开本发明的一个实施方案的制备实例。这种方法方式原则上也可以用于所有其它公开的脱氧核糖核酸和酶，以使得可以以类似途径制备所有的本发明的酶和脱氧核糖核酸。
所述脱氧核糖核酸可以连接到载体，优选质粒中。
作为空载体，可以例如使用pET-20b(+)、pET-21a-d(+)、pET-22b(+)、pET-23a-d(+)、pET-24a-d(+)、pET-25b(+)、pET-26b(+)、pET-27b(+)、pET-28a(+)、pET-29a-c(+)、
pET-30a-c(+)、pET-31b(+)、pET-34b(+)、pET-35b(+)、pET-36b(+)、pET-37b(+)、pET-38b(+)，向其中连接相应的本发明DNA。
替代地，也可以将该脱氧核糖核酸连接到基因组中。
连接的脱氧核糖核酸是DNA序列，其编码酶ApPDC-E469G的变体并在位置号1402-1404中编码具有相对于异亮氨酸减小的占据空间的氨基酸。这些脱氧核糖核酸也可以编码酶ApPDC-E469G-I468L、ApPDC-E469G-I468T、ApPDC-E469G-I468C或ApPDC-E469G-I468S。
优选地，连接的脱氧核糖核酸编码根据序列1、2和3的蛋白。
根据本发明可以提供载体，其含有编码酶ApPDC-E469G的变体并在位置号1402-1404 中编码具有相对于异亮氨酸减小或相等的占据空间的氨基酸的脱氧核糖核酸。
优选地，该载体含有根据序列号4的脱氧核糖核酸。
优选地，该载体是质粒。
图1展示了本发明的质粒（pET-21 a(+)载体卡）。
在序列号5中例如示出本发明质粒的DNA序列，其含有根据序列号4的DNA。
根据本发明，借助在位置号468中具有相对于异亮氨酸具有减小的占据空间的氨基酸的酶ApPDC-E469G的变体，优选选自序列号 1、2或3的酶，使苯甲醛与丙酮酸或与乙醛根据式(1)反应成(S)-苯基乙酰基甲醇。
式(1)
Figure 304379DEST_PATH_IMAGE001
该反应优选在水溶液中进行。
pH值为5 - 9，优选6.5 - 8，特别优选6.5 - 7。
对此，可以使用例如磷酸钾缓冲液、HEPES、MOPS、TEA或TRIS-HCl作为缓冲液。
此外，可以使用磷酸硫胺素和硫酸镁作为辅因子。
该反应可以在体内或在体外进行。
对于在体内生产(S)-苯基乙酰基甲醇，可以使用例如大肠杆菌、棒状杆菌例如谷氨酸棒状杆菌或酵母例如酿酒酵母作为生产生物体。
为此，该生产生物体通过本发明的DNA或包含该DNA的载体进行转化。
该DNA也可以在生产生物体中引入基因组中。
所用的基因在此异源表达。
对于在体外生产，可以使用该生产生物体的分离的酶或细胞提取物。
典型温度为20℃至40℃，优选20℃至30℃，特别优选为20℃至25℃的温度。
反应时间可以为2h - 48 h，优选6h - 24h，特别优选12 h。
下面介绍若干实施例，其不解释为具有限制性。
这些反应可以以经典的配方（Ansatz）在反应烧瓶中在搅拌下进行。
为了能够以高对映体过量制备(S)-PAC，通过诱变产生酶ApPDC-E469G的变体。变体ApPDC-E469G-I468G通过使用粗细胞提取物酶以85 %ee生产(S)-PAC。通过使用在大肠杆菌中异源表达并用作廉价全细胞催化剂的ApPDC-E469G-I468G，可以以 93 % ee生成(S)-PAC。
实施例1：
20 mM苯甲醛、400 mM丙酮酸、2.5 mM硫酸镁、100 µM二磷酸硫胺素、20 mg/mL（湿重）ApPDC-E469G-I468G（大肠杆菌的全细胞，其中ApPDC-E469G-I468G以表达形式存在）、50mM磷酸钾缓冲液pH 6.5，25 ℃，反应时间：48 h。
(S)-PAC的对映体纯度： ee 93 %
收率：67 %。
实施例2：
20 mM苯甲醛、400 mM丙酮酸、2.5 mM硫酸镁、100 µM二磷酸硫胺素、1 mg/mLApPDC-E469G-I468G（大肠杆菌的粗细胞提取物，其中ApPCD-E469G-I468G以表达形式存在）、50 mM磷酸钾缓冲液pH 6.5，25 ℃，反应时间：48 h。
(S)-PAC的对映体纯度： ee 85 %。
下面示例性阐述本发明的酶和编码其的脱氧核糖核酸的制备。所示方法原则上也可以类似地用于制备其它的本发明裂解酶和编码其的脱氧核糖核酸。
酶变体ApPDC-E469G-I468G的DNA的制备
“位点饱和诱变”
根据Reetz等人（Reetz, Kahakeaw等人2008）的变体的所谓的“位点饱和诱变”的方法由基因序列ApPDC-E469G（模板DNA）起始进行，以获得在位置号I468上的氨基酸替换。在这一方法中，使用编码20种天然氨基酸中的12种的NDT-密码子。
聚合酶链反应（PCR）
在最初的步骤中，借助聚合酶链反应（PCR）复制模板DNA，并在此同时通过使用所谓的简并引物（degenerierten Primer）和NDT密码子插入（eingefügt）突变。所用的引物从“Eurofins MWG Operon”公司订购（http://www.eurofinsgenomics.eu）并具有下列序列：
用于制备ApPDC-E469G-I468NDT的位点饱和诱变的引物
正向：5´ CCGTGGCTATGTCNDTGGCATCGCCATTC 3´（序列号6）
反向：5´ GAATGGCGATGCCAHNGACATAGCCACGG 3´（序列号7）。
首先制备母液并随后分为四个各为50 µl的配制品。为了开始该反应，添加1 µl“KOD热启动聚合酶”。
PCR-反应配方：
Figure 221519DEST_PATH_IMAGE002
该反应在下列条件下进行：
Figure 686742DEST_PATH_IMAGE003
为了消化模板DNA，将1 µl的酶DpnI（Eppendorf）添加到溶液中并在37℃下培养1h。整个配制品然后用“DNA纯化试剂盒”（化学品列表）在进一步转化前进行提纯。
大肠杆菌BL21-DE3和大肠杆菌DH5α的转化
菌株大肠杆菌BL21-DE3和大肠杆菌DH5α用通过“位点饱和诱变”制备的DNA进行转化。为此，向50 µl感受态细胞中添加100 ng DNA并在冰上培养30分钟。随后在42 ℃下进行热休克90秒。3分钟后，向冰上添加500 µl SOC培养基并然后将该溶液在350转/分钟下且在37 ℃ 下在Eppendorf恒温混匀仪中培养45分钟。在完成培养后，将细胞悬浮液在13000转/分钟下在Eppendorf台式离心机中离心分离30秒，并将沉淀物（Pellet）接着再悬浮在100 µl上清液中。浓缩至100 µl的细胞悬浮液在LB琼脂平板（具有100 µg/ml氨苄青霉素）上铺板并在37 ℃下倒立着培养16 h。
酶变体的表达
转化的46个单菌落从板上用牙签挖出并在20 ℃和850转/分钟下在48孔Nerbe板（Nerbe Plus GmbH）的各具有1 ml LB培养基的孔（“母板”）中分别培养24 h。另一个孔用大肠杆菌 BL 21-DE3细胞接种，其事前与ApPDC-E469G-模板DNA 类似地转化。在完成培养后，在48孔FlowerPlates®（m2p-labs, 德国）中向各1.5 ml自动诱导培养基中加入10 µl细胞悬浮液。该FlowerPlate在20 ℃和850转/分钟下培养48 h。向“母板”的剩余体积（990 µl）加入300 µl甘油并在-80 ℃下储存。
细胞分解和碳连接
将FlowerPlates®中表达的变体通过冷冻（48 h， 4℃）分解。在重新解冻后，将各500 µl的细胞悬浮液转移到96孔板的两个孔中（双重测定）。将该板在4000转/分钟下离心3分钟并将沉淀物再悬浮到具有1 mg/ml溶菌酶的420 µl Kpi缓冲液中。该板在20 ℃和400转/分钟下培养1 h并随后重新在4000转/分钟下离心10分钟。将各250 µl 上清液移液到2ml Nerbe板的各一个孔中并添加由40 mM苯甲醛、400 mM丙酮酸、4 mM硫酸镁和400 µM二磷酸硫胺素形成的250 µl反应溶液。该板重新培养24 h并随后分析反应溶液（参见HPLC分析）。
HPLC分析
向200 µl碳连接反应溶液加入各200 µl庚烷，涡旋并随后将各150 µl 的上部相转移到HPLC 小瓶中。样品分析通过Chiralpak IC-3 柱（Chiral Technologies Inc.）在使用下列方法的情况下进行。
HPLC程序
Figure 81951DEST_PATH_IMAGE004
典型的保留时间和用于定量的波长
Figure 834007DEST_PATH_IMAGE005
DNA分离和通过DNA测序的最佳酶变体的识别
将碳连接反应中对于(S)-PAC提供最高ee值的酶的DNA由母板起始进行测序以识别突变。为此，首先将细胞用接种环从加入有甘油的母板转移到50 mL LB培养基（+50 µg/ml氨苄青霉素）中并在250 mL锥形瓶中在37 ℃下培养。在12 h培养后，将20 mL细胞悬浮液离心分离（4000转/分钟，5 min，4 ℃）。沉淀物中的细胞的DNA类似于制造商说明（QiagenN.V.）根据“QIAprep® Spin Miniprep Kit”方法进行分离。为此，将DNA的浓度设定为100ng/µl并通过LGC Genomics GmbH公司测序。
LB（溶菌肉汤）培养基
Figure 656469DEST_PATH_IMAGE007
借助QuikChange®制备变体ApPDC-E469G-I468G的替代的定向方法
制备酶变体ApPDC-E469G/I468G的另一方法例如是所谓的QuikChange®-PCR法（U.S.专利号5.789.166、5.932.419、6.391.548）。在PCR的这一变体的情况中，使用在待替换的DNA三联体密码的位置上带有相应的序列修饰的引物对。为了制备酶变体ApPDC-E469G/I468G，可以使用编码变体 ApPDC-E469G的基因。这一所谓的DNA模板应在载体（例如pET22a）中以克隆形式存在。代替在位置I468中编码氨基酸色氨酸的三联体密码，必须使用在该位置上带有编码甘氨酸的突变的引物（即GGA、GGT、GGC或GGG）。这种QuikChange®-PCR法的所有其它参数以及所需引物的选择可以类似于制造商说明（Agilent Technologies,Inc.）借助“QuikChange®定点诱变试剂盒”的指导来进行。
用于制备变体ApPDC-E469G-I468G的QuikChange®-PCR法的DNA模板（ApPDC- E469G）
Figure 861186DEST_PATH_IMAGE008
Figure 60086DEST_PATH_IMAGE009
。
在序列表中，该序列以序列号8示出。序列号8在此例如对于编码根据序列号53的待修饰的蛋白ApPDC-E469G的DNA公开。但是，根据本发明，编码待修饰的起始蛋白的所有其它脱氧核糖核酸可以用于制备待修饰的酶。为其编码的核苷酸是本领域技术人员已知的。
“全细胞”形式的变体的制备
为了以1L的规模在全细胞中表达酶，首先将细胞从加入有甘油的母板用接种环转移到50 mL LB培养基（+100 µg/ml氨苄青霉素）中并在250 mL锥形瓶中在120转/分钟和37℃下培养。在16 h培养后，向1 L自动诱导培养基中加入10 mL培养物并在5 L锥形瓶中在90转/分钟和20 ℃下培养72 h。随后通过离心（4 ℃，6000转/分钟，30 min）收获该细胞并在-20 ℃下储存以进一步使用。
自动诱导培养基
12 g/l 蛋白胨
24 g/l 酵母提取物
90 mM 磷酸钾缓冲液(pH 7.5)
0.5 g/l 葡萄糖
2 g/l 乳糖
0.01 g/l 氨苄青霉素
6.3 g/l 甘油
“细胞提取物”形式的变体的制备
将10 g以1L规模培养的细胞（参见““全细胞”形式的变体的制备”）用冷却到4 ℃的25 mL破碎缓冲液（50 mM磷酸钾pH6.5、100 µM二磷酸硫胺素、2 mM硫酸镁）在冰上再悬浮。随后，将再悬浮的细胞借助超声（SD14超声波发生器（Hielscher Ultrasonics GmbH），4x2 min超声处理，各1分钟来自冰的冷却）进行破碎。为了分离细胞碎片，将该溶液离心分离（45 min，18000转/分钟，4 ℃）并将上清液（“细胞提取物”） 转移到新容器中。
“分离的酶”形式的变体的制备
为了借助固定化金属离子亲合色谱法和尺寸排阻色谱法提纯ApPDC变体，使用“Amersham Bioscience”公司的“ÄKTA™purifier”，以尤其检测蛋白-UV吸收（280 nm）以及导电性并调节流速。为了提纯，将25 mL制备的细胞提取物（参见““细胞提取物”形式的变体的制备”）以3 mL/min的流速施加到体积为60 mL的柱Ni-NTA-Superflow（Qiagen N.V.）上，其事前用180 mL上样缓冲液进行平衡。随后，继续用上样缓冲液以5 ml/min的流速冲洗，以除去不结合或非常弱地结合在柱材料上的蛋白。在UV吸收（280 nm）重新达到稳定基线后，漂洗缓冲液（50 mM磷酸钾pH 6.5、100 µM二磷酸硫胺素、2 mM硫酸镁、50 mM咪唑）以5mL/min流速用于洗脱弱结合在柱材料上的蛋白。在重新达到稳定UV吸收（280 nm）后，以5mL/min的流速使用洗脱缓冲液（50 mM磷酸钾pH 6.5、100 µM二磷酸硫胺素、2 mM硫酸镁、250 mM咪唑）以洗脱目标蛋白。
将IMAC的洗出液以10 mL/min的流速施加到尺寸排阻色谱柱（1 L柱体积，Sephadex-G25，GE-Health-care）上以进行再缓冲，该柱事先用2 L再缓冲缓冲液（10 mM磷酸钾pH 6.5、100 µM二磷酸硫胺素、2 mM硫酸镁）冲洗。合并具有提高的UV吸收（280 nm）的级分并在结晶皿中冷冻（-20 ℃）。为了冻干，向冷冻的蛋白溶液施加0.22 mBar的负压3天。
在本发明的另一个有利配置中，本发明的酶除了在位置号468中的根据本发明的替换之外，氨基酸色氨酸还在位置号543中被比色氨酸具有更小的占据空间的氨基酸替换。
这些裂解酶此外还对在制备(S)-苯基乙酰基甲醇时提高立体选择性具有有利影响。
通过本发明的这一优选的实施方案，可以实现98 % ee的对映体过量。
优选地，可以提及满足这些要求的下列裂解酶：
- 根据序列号9在位置号543中具有组氨酸的ApPCD-E469G-I468G-W543H
- 根据序列号10在位置号543中具有苯丙氨酸的ApPCD-E469G-I468G-W543F
- 根据序列号11在位置号543中具有脯氨酸的ApPCD-E469G-I468G-W543P
- 根据序列号12在位置号543中具有异亮氨酸的ApPCD-E469G-I468G-W543I
- 根据序列号13在位置号543中具有亮氨酸的ApPCD-E469G-I468G-W543L
- 根据序列号14在位置号543中具有甲硫氨酸的ApPCD-E469G-I468G-W543M
- 根据序列号15在位置号543中具有缬氨酸的ApPCD-E469G-I468G-W543V
- 根据序列号16在位置号543中具有丙氨酸的ApPCD-E469G-I468G-W543A
- 根据序列号17在位置号543中具有酪氨酸的ApPCD-E469G-I468G-W543Y
- 根据序列号18在位置号543中具有苏氨酸的ApPCD-E469G-I468G-W543T
- 根据序列号19在位置号543中具有甘氨酸的ApPCD-E469G-I468G-W543G
- 根据序列号20在位置号543中具有丝氨酸的ApPCD-E469G-I468G-W543S
- 根据序列号21在位置号543中具有半胱氨酸ApPCD-E469G-I468G-W543C
以及
- 根据序列号22在位置号543中具有组氨酸的ApPCD-E469G-I468A-W543H
- 根据序列号23在位置号543中具有苯丙氨酸的ApPCD-E469G-I468A-W543F
- 根据序列号24在位置号543中具有脯氨酸的ApPCD-E469G-I468A-W543P
- 根据序列号25在位置号543中具有异亮氨酸的ApPCD-E469G-I468A-W543I
- 根据序列号26在位置号543中具有亮氨酸的ApPCD-E469G-I468A-W543L
- 根据序列号27在位置号543中具有甲硫氨酸的ApPCD-E469G-I468A-W543M
- 根据序列号28在位置号543中具有缬氨酸的ApPCD-E469G-I468A-W543V
- 根据序列号29在位置号543中具有丙氨酸的ApPCD-E469G-I468A-W543A
- 根据序列号30在位置号543中具有酪氨酸的ApPCD-E469G-I468A-W543Y
- 根据序列号31在位置号543中具有苏氨酸的ApPCD-E469G-I468A-W543T
- 根据序列号32在位置号543中具有甘氨酸的ApPCD-E469G-I468A-W543G
- 根据序列号33在位置号543中具有丝氨酸的ApPCD-E469G-I468A-W543S
- 根据序列号34在位置号543中具有半胱氨酸的ApPCD-E469G-I468A-W543C
和
- 根据序列号35在位置号543中具有组氨酸的ApPCD-E469G-I468V-W543H
- 根据序列号36在位置号543中具有苯丙氨酸的ApPCD-E469G-I468V-W543F
- 根据序列号37在位置号543中具有脯氨酸的ApPCD-E469G-I468V-W543P
- 根据序列号38在位置号543中具有异亮氨酸的ApPCD-E469G-I468V-W543I
- 根据序列号39在位置号543中具有亮氨酸的ApPCD-E469G-I468V-W543L
- 根据序列号40在位置号543中具有甲硫氨酸的ApPCD-E469G-I468V-W543M
- 根据序列号41在位置号543中具有缬氨酸的ApPCD-E469G-I468V-W543V
- 根据序列号42在位置号543中具有丙氨酸的ApPCD-E469G-I468V-W543A
- 根据序列号43在位置号543中具有酪氨酸的ApPCD-E469G-I468V-W543Y
- 根据序列号44在位置号543中具有苏氨酸的ApPCD-E469G-I468V-W543T
- 根据序列号45在位置号543中具有甘氨酸的ApPCD-E469G-I468V-W543G
- 根据序列号46在位置号543中具有丝氨酸的ApPCD-E469G-I468V-W543S
- 根据序列号47在位置号543中具有半胱氨酸的ApPCD-E469G-I468V-W543C。
此外，根据本发明提供编码所述酶的脱氧核糖核酸。
根据本发明，这是编码酶ApPDC-E469G 的变体并在位置号1402-1404中编码具有相对于异亮氨酸减小的占据空间的氨基酸且此外在位置号1627-1629中编码比色氨酸较小占据空间的氨基酸的脱氧核糖核酸。
对于根据序列号23的蛋白的实例，可以在相应脱氧核糖核酸的位置号1402-1404中例如存在核酸GCC并在位置号1627-1629中存在核酸TTT。相应的核苷酸序列在序列表中列在编号48下。
编码根据序列9至47的本发明酶的DNA可以根据本领域技术人员已知的方法通过定向或不定向的诱变来产生。在此，优选的是定向诱变。这些方法是本领域技术人员已知的。在具体的描述部分中，具体公开本发明的一个实施方案的制备实例。这种方法方式原则上也可以用于所有其它公开的脱氧核糖核酸和酶，以使得可以以类似途径制备所有的本发明的酶和脱氧核糖核酸。
所述脱氧核糖核酸可以连接到载体，优选质粒中。
作为空载体，可以例如使用pET-20b(+)、pET-21a-d(+)、pET-22b(+)、pET-23a-d(+)、pET-24a-d(+)、pET-25b(+)、pET-26b(+)、pET-27b(+)、pET-28a(+)、pET-29a-c(+)、pET-30a-c(+)、pET-31b(+)、pET-34b(+)、pET-35b(+)、pET-36b(+)、pET-37b(+)、pET-38b(+)，向其中连接相应的本发明DNA。
替代地，也可以将该脱氧核糖核酸连接到基因组中。
连接的脱氧核糖核酸是DNA，其编码酶ApPDC-E469G的变体并在位置号1402-1404中编码具有相对于异亮氨酸减小的占据空间的氨基酸且在位置号1627-1629中编码具有相对于色氨酸减小的占据空间的氨基酸。
优选地，连接的脱氧核糖核酸编码根据序列9至47的蛋白。
根据本发明可以提供载体，其含有编码酶ApPDC-E469G的变体并在位置号1402-1404 中编码具有相对于异亮氨酸减小的占据空间的氨基酸且在位置号1627-1629中编码具有相对于色氨酸减小的占据空间的氨基酸的脱氧核糖核酸。
优选地，该载体含有根据序列号48的脱氧核糖核酸。
优选地，该载体是质粒。
在序列号49中例如示出本发明质粒的序列，其含有根据序列号48的DNA。
根据本发明，还在本发明的有利配置中借助在位置号468中存在具有相对于异亮氨酸减小的占据空间的氨基酸且在位置号543中存在具有相对于色氨酸减小的占据空间的氨基酸的酶ApPDC-E469G的变体，优选选自根据序列号9至47的酶，使苯甲醛与丙酮酸或与乙醛根据式(1)反应成(S)-苯基乙酰基甲醇。
式(1)
Figure 666648DEST_PATH_IMAGE010
该反应优选在水溶液中进行。
pH值为5 - 9，优选6.5 - 8，特别优选6.5 - 7。
对此，可以使用例如磷酸钾缓冲液、HEPES、MOPS、TEA或TRIS-HCl作为缓冲液。
此外，可以使用磷酸硫胺素和硫酸镁作为辅因子。
该反应可以在体内或在体外进行。
对于在体内生产(S)-苯基乙酰基甲醇，可以使用例如大肠杆菌、棒状杆菌例如谷氨酸棒状杆菌或酵母例如酿酒酵母作为生产生物体。
为此，该生产生物体通过本发明的DNA或包含该DNA的载体进行转化。
该DNA也可以在生产生物体中引入基因组中。
所用的基因在此异源表达。
对于在体外生产，可以使用该生产生物体的分离的酶或细胞提取物。
典型温度为20℃至40℃，优选20℃至30℃，特别优选为20℃至25℃的温度。
反应时间可以为2h - 48 h，优选6h - 24h，特别优选12 h。
下面介绍若干实施例，其不解释为具有限制性。
这些反应可以以经典的配方在反应烧瓶中在搅拌下进行。
为了能够以高对映体过量制备(S)-PAC，通过诱变产生酶ApPDC-E469G的变体。变体ApPDC-E469G-I468A-W543F通过使用分离的酶以98 %ee生产(S)-PAC。通过使用在大肠杆菌中异源表达并用作廉价全细胞催化剂的ApPDC-E469G-I468A-W543F，可以以 96% ee生成(S)-PAC。
实施例3：
20 mM苯甲醛、400 mM丙酮酸、2.5 mM硫酸镁、100 µM二磷酸硫胺素、20 mg/mL（湿重）ApPDC-E469G-I468A-W543F（大肠杆菌的全细胞，其中ApPDC-E469G-I468A-W543F以表达形式存在）、50 mM磷酸钾缓冲液
pH 6.5，25 ℃，反应时间：48 h。
(S)-PAC的对映体纯度： ee 96 %
收率：73 %。
实施例4：
20 mM苯甲醛、400 mM丙酮酸、2.5 mM硫酸镁、100 µM二磷酸硫胺素、1 mg/mLApPDC-E469G-I468A-W543F 20 mM苯甲醛、400 mM丙酮酸、2.5 mM硫酸镁、100 µM二磷酸硫胺素、1 mg/mL ApPDC-E469G-I468G（分离的酶）、50 mM磷酸钾缓冲液pH 6.5，25 ℃，反应时间：48 h。，50 mM磷酸钾缓冲液pH 6.5，25 ℃，反应时间：48 h。
(S)-PAC的对映体纯度： ee 98 %
收率：45 %。
借助QuikChange®由ApPDC-E469G-I468A-W543起始制备变体ApPDC-E469G-I468A-W543F的定向方法
为了制备酶变体ApPDC-E469G-I468A-W543F，使用所谓的QuikChange®-PCR法（U.S.专利号5.789.166、5.932.419、6.391.548）。在PCR的这一变体的情况中，使用在待替换的DNA三联体密码的位置上带有相应的序列修饰的引物对。为了制备酶变体ApPDC-E469G-I468A-W543F，使用编码变体ApPDC-E469G-I468A-W543的基因。这一所谓的DNA模板在载体（例如pET22a）中以克隆形式存在。代替在位置W543中编码氨基酸色氨酸的三联体密码，必须使用在该位置上带有编码苯丙氨酸的突变的引物（即例如TTC或TTT）。
用于由ApPDC-E469G-I468A-W543起始制备酶变体ApPDC-E469G-I468A-W543F的 QuikChange®-PCR法的引物
正向：5´ accttgcggccgaattgaaccagcatatccgtgc 3´（序列号50）
反向：5´ gcacggatatgctggttcaattcggccgcaaggt 3´（序列号51）。
首先制备母液并随后分为四个各为50 µl的配制品。为了开始该反应，添加1 µl“PfuTurbo® DNA聚合酶”。
PCR-反应配方：
Figure 660011DEST_PATH_IMAGE012
该反应在下列条件下进行：
Figure 352024DEST_PATH_IMAGE013
为了消化模板DNA，将1 µl的酶DpnI（Eppendorf）添加到溶液中并在37℃下培养1h。整个配制品然后用“DNA纯化试剂盒”（化学品列表）在进一步转化前进行提纯。
这一QuikChange®-PCR法的所有其它参数以及对于其它酶变体的所需引物的选择可以类似于制造商（Agilent Technologies, Inc.）的说明借助 “QuikChange®定点诱变试剂盒”的指导来使用。
制备变体ApPDC-E469G-I468A-W543F的 QuikChange®-PCR法的DNA模板（ApPDC- E469G-I468A）
Figure 89036DEST_PATH_IMAGE014
Figure 612421DEST_PATH_IMAGE015
Figure 979948DEST_PATH_IMAGE016
。
序列号52在此例如对于编码根据序列号2的待修饰的蛋白ApPDC-E469G-I468A的DNA公开。但是，根据本发明，编码待修饰的起始蛋白的所有其它脱氧核糖核酸可以用于制备待修饰的酶。为其编码的核苷酸是本领域技术人员已知的。
大肠杆菌BL21-DE3和大肠杆菌DH5α的转化
菌株大肠杆菌BL21-DE3和大肠杆菌DH5α用通过“位点饱和诱变”制备的DNA进行转化。为此，向50 µl感受态细胞中添加100 ng DNA并在冰上培养30分钟。随后在42 ℃下进行热休克90秒。3分钟后，向冰上添加500 µl SOC培养基并然后将该溶液在350转/分钟下且在37 ℃ 下在Eppendorf恒温混匀仪中培养45分钟。在完成培养后，将细胞悬浮液在13000转/分钟下在Eppendorf台式离心机中离心分离30秒，并将沉淀物接着再悬浮在100 µl上清液中。浓缩至100 µl的细胞悬浮液在LB琼脂平板（具有100 µg/ml氨苄青霉素）上铺板并在37℃下倒立着培养16 h。
DNA分离和通过DNA测序的最佳酶变体的识别
将碳连接反应中对于(S)-PAC提供最高ee值的酶的DNA由母板起始进行测序以识别突变。为此，首先将细胞用接种环从加入有甘油的母板转移到50 mL LB培养基（+50 µg/ml氨苄青霉素）中并在250 mL锥形瓶中在37 ℃下培养。在12 h培养后，将20 mL细胞悬浮液离心分离（4000转/分钟，5 min，4 ℃）。沉淀物中的细胞的DNA类似于制造商说明（QiagenN.V.）根据“QIAprep® Spin Miniprep Kit”方法进行分离。为此，将DNA的浓度设定为100ng/µl并通过LGC Genomics GmbH公司测序。
LB（溶菌肉汤）培养基
Figure DEST_PATH_IMAGE017
“全细胞”形式的变体的制备
为了以1L的规模在全细胞中表达酶，首先将细胞从加入有甘油的母板用接种环转移到50 mL LB培养基（+100 µg/ml氨苄青霉素）中并在250 mL锥形瓶中在120转/分钟和37℃下培养。在16 h培养后，向1 L自动诱导培养基中加入10 mL培养物并在5 L锥形瓶中在90转/分钟和20 ℃下培养72 h。随后通过离心（4 ℃，6000转/分钟，30 min）收获该细胞并在-20 ℃下储存以进一步使用。
自动诱导培养基
12 g/l 蛋白胨
24 g/l 酵母提取物
90 mM 磷酸钾缓冲液(pH 7.5)
0.5 g/l 葡萄糖
2 g/l 乳糖
0.01 g/l 氨苄青霉素
6.3 g/l 甘油
分离的酶的形式的变体的制备
将10 g以1L规模培养的细胞用冷却到4 ℃ 的25 mL破碎缓冲液（50 mM磷酸钾pH6.5、100 µM二磷酸硫胺素、2 mM硫酸镁）在冰上再悬浮。随后，将再悬浮的细胞借助超声（SD14超声波发生器（Hielscher Ultrasonics GmbH），4x2 min超声处理，各1分钟来自冰的冷却）进行破碎。为了分离细胞碎片，将该溶液离心分离（45 min，18000转/分钟，4 ℃）并将上清液（“细胞提取物”） 转移到新容器中。
为了借助固定化金属离子亲合色谱法和尺寸排阻色谱法提纯ApPDC变体，使用“Amersham Bioscience”公司的“ÄKTA™purifier”，以尤其检测蛋白-UV吸收（280 nm）以及导电性并调节流速。为了提纯，将制备的细胞提取物（~25 mL）以3 mL/min的流速施加到体积为60 mL的柱Ni-NTA-Superflow（Qiagen N.V.）上 ，其事前用180 mL上样缓冲液进行平衡。随后，继续用上样缓冲液以5 ml/min的流速冲洗，以除去不结合或非常弱地结合在柱材料上的蛋白。在UV吸收（280 nm）重新达到稳定基线后，漂洗缓冲液（50 mM磷酸钾pH 6.5、100 µM二磷酸硫胺素、2 mM硫酸镁、50 mM咪唑）以5 mL/min流速用于洗脱弱结合在柱材料上的蛋白。在重新达到稳定UV吸收（280 nm）后，以5 mL/min的流速使用洗脱缓冲液（50 mM磷酸钾pH 6.5、100 µM二磷酸硫胺素、2 mM硫酸镁、250 mM咪唑）以洗脱目标蛋白。
将IMAC的洗出液以10 mL/min的流速施加到尺寸排阻色谱柱（1 L柱体积,Sephadex-G25, GE-Healthcare）上以进行再缓冲，该柱事先用2 L再缓冲缓冲液（10 mM磷酸钾pH 6.5、100 µM二磷酸硫胺素、2 mM硫酸镁）冲洗。合并具有提高的UV吸收（280 nm）的级分并在结晶皿中冷冻（-20 ℃）。为了冻干，向冷冻的蛋白溶液施加0.22 mBar的负压3天。所产生的粉末的蛋白含量为20 %。纯度（目标蛋白相对于外源蛋白的含量）为>90 %。
序列表
<110> Forschungszentrum Jülich GmbH
<120> 裂解酶以及不对称合成苯基乙酰基甲醇的方法
<130> PT1.2668
<160> 53
<170> PatentIn version 3.5
<210> 1
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 1
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Trp Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 2
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 2
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Trp Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 3
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 3
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Trp Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 4
<211> 1680
<212> DNA
<213> 人工
<220>
<223> 人工制备
<400> 4
atgacctata ctgttggcat gtatcttgca gaacgccttg tacagatcgg gctgaagcat 60
cacttcgccg tggcgggcga ctacaatctc gttcttctgg atcagttgct cctcaacaag 120
gacatgaaac agatctattg ctgcaatgag ttgaactgtg gcttcagcgc ggaaggctac 180
gcccgttcta acggggctgc ggcagcggtt gtcaccttca gcgttggcgc catttccgcc 240
atgaacgccc tcggcggcgc ctatgccgaa aacctgccgg ttatcctgat ttccggcgcg 300
cccaacagca atgatcaggg cacaggtcat atcctgcatc acacaatcgg caagacggat 360
tacagctacc agcttgaaat ggcccgtcag gtcacctgtg ccgccgaaag cattaccgac 420
gctcactccg ccccggccaa gattgaccac gtcattcgca cggcgctgcg cgagcgtaag 480
ccggcctatc tggacatcgc gtgcaacatt gcctccgagc cctgcgtgcg gcctggccct 540
gtcagcagcc tgctgtccga gcctgaaatc gaccacacga gcctgaaggc cgcagtggac 600
gccacggttg ccttgctgga aaaatcggcc agccccgtca tgctgctggg cagcaagctg 660
cgggccgcca acgcactggc cgcaaccgaa acgctggcag acaagctgca atgcgcggtg 720
accatcatgg cggccgcgaa aggctttttc cccgaagacc acgcgggttt ccgcggcctg 780
tactggggcg aagtctcgaa ccccggcgtg caggaactgg tggagacctc cgacgcactg 840
ctgtgcatcg cccccgtatt caacgactat tcaacagtcg gctggtcggc atggcccaag 900
ggccccaatg tgattctggc tgagcccgac cgcgtaacgg tcgatggccg cgcctatgac 960
ggctttaccc tgcgcgcctt cctgcaggct ctggcggaaa aagcccccgc gcgcccggcc 1020
tccgcacaga aaagcagcgt cccgacgtgc tcgctcaccg cgacatccga tgaagccggt 1080
ctgacgaatg acgaaatcgt ccgtcatatc aacgccctgc tgacatcaaa cacgacgctg 1140
gtggcagaaa ccggcgattc atggttcaat gccatgcgca tgaccctgcc gcgcggtgcg 1200
cgcgtggaac tggaaatgca gtggggccat atcggctggt ccgtgccctc cgccttcggc 1260
aatgccatgg gctcgcagga ccgccagcat gtggtgatgg taggcgatgg ctccttccag 1320
cttaccgcgc aggaagtggc tcagatggtg cgctacgaac tgcccgtcat tatctttctg 1380
atcaacaacc gtggctatgt cggtggcatc gccattcatg acggcccgta caactatatc 1440
aagaactggg attacgccgg cctgatggaa gtcttcaacg ccggagaagg ccatggactt 1500
ggcctgaaag ccaccacccc gaaggaactg acagaagcca tcgccagggc aaaagccaat 1560
acccgcggcc cgacgctgat cgaatgccag atcgaccgca cggactgcac ggatatgctg 1620
gttcaatggg gccgcaaggt tgcctcaacc aacgcgcgca agaccactct ggccctcgag 1680
<210> 5
<211> 7041
<212> DNA
<213> 人工
<220>
<223> 人工制备
<400> 5
tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60
cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120
ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180
gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240
acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300
ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360
ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420
acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480
tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540
tccgctcatg agacaataac cctgataaat gcttcaataa tattgaaaaa ggaagagtat 600
gagtattcaa catttccgtg tcgcccttat tccctttttt gcggcatttt gccttcctgt 660
ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct gaagatcagt tgggtgcacg 720
agtgggttac atcgaactgg atctcaacag cggtaagatc cttgagagtt ttcgccccga 780
agaacgtttt ccaatgatga gcacttttaa agttctgcta tgtggcgcgg tattatcccg 840
tattgacgcc gggcaagagc aactcggtcg ccgcatacac tattctcaga atgacttggt 900
tgagtactca ccagtcacag aaaagcatct tacggatggc atgacagtaa gagaattatg 960
cagtgctgcc ataaccatga gtgataacac tgcggccaac ttacttctga caacgatcgg 1020
aggaccgaag gagctaaccg cttttttgca caacatgggg gatcatgtaa ctcgccttga 1080
tcgttgggaa ccggagctga atgaagccat accaaacgac gagcgtgaca ccacgatgcc 1140
tgcagcaatg gcaacaacgt tgcgcaaact attaactggc gaactactta ctctagcttc 1200
ccggcaacaa ttaatagact ggatggaggc ggataaagtt gcaggaccac ttctgcgctc 1260
ggcccttccg gctggctggt ttattgctga taaatctgga gccggtgagc gtgggtctcg 1320
cggtatcatt gcagcactgg ggccagatgg taagccctcc cgtatcgtag ttatctacac 1380
gacggggagt caggcaacta tggatgaacg aaatagacag atcgctgaga taggtgcctc 1440
actgattaag cattggtaac tgtcagacca agtttactca tatatacttt agattgattt 1500
aaaacttcat ttttaattta aaaggatcta ggtgaagatc ctttttgata atctcatgac 1560
caaaatccct taacgtgagt tttcgttcca ctgagcgtca gaccccgtag aaaagatcaa 1620
aggatcttct tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa caaaaaaacc 1680
accgctacca gcggtggttt gtttgccgga tcaagagcta ccaactcttt ttccgaaggt 1740
aactggcttc agcagagcgc agataccaaa tactgtcctt ctagtgtagc cgtagttagg 1800
ccaccacttc aagaactctg tagcaccgcc tacatacctc gctctgctaa tcctgttacc 1860
agtggctgct gccagtggcg ataagtcgtg tcttaccggg ttggactcaa gacgatagtt 1920
accggataag gcgcagcggt cgggctgaac ggggggttcg tgcacacagc ccagcttgga 1980
gcgaacgacc tacaccgaac tgagatacct acagcgtgag ctatgagaaa gcgccacgct 2040
tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa caggagagcg 2100
cacgagggag cttccagggg gaaacgcctg gtatctttat agtcctgtcg ggtttcgcca 2160
cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc tatggaaaaa 2220
cgccagcaac gcggcctttt tacggttcct ggccttttgc tggccttttg ctcacatgtt 2280
ctttcctgcg ttatcccctg attctgtgga taaccgtatt accgcctttg agtgagctga 2340
taccgctcgc cgcagccgaa cgaccgagcg cagcgagtca gtgagcgagg aagcggaaga 2400
gcgcctgatg cggtattttc tccttacgca tctgtgcggt atttcacacc gcatatatgg 2460
tgcactctca gtacaatctg ctctgatgcc gcatagttaa gccagtatac actccgctat 2520
cgctacgtga ctgggtcatg gctgcgcccc gacacccgcc aacacccgct gacgcgccct 2580
gacgggcttg tctgctcccg gcatccgctt acagacaagc tgtgaccgtc tccgggagct 2640
gcatgtgtca gaggttttca ccgtcatcac cgaaacgcgc gaggcagctg cggtaaagct 2700
catcagcgtg gtcgtgaagc gattcacaga tgtctgcctg ttcatccgcg tccagctcgt 2760
tgagtttctc cagaagcgtt aatgtctggc ttctgataaa gcgggccatg ttaagggcgg 2820
ttttttcctg tttggtcact gatgcctccg tgtaaggggg atttctgttc atgggggtaa 2880
tgataccgat gaaacgagag aggatgctca cgatacgggt tactgatgat gaacatgccc 2940
ggttactgga acgttgtgag ggtaaacaac tggcggtatg gatgcggcgg gaccagagaa 3000
aaatcactca gggtcaatgc cagcgcttcg ttaatacaga tgtaggtgtt ccacagggta 3060
gccagcagca tcctgcgatg cagatccgga acataatggt gcagggcgct gacttccgcg 3120
tttccagact ttacgaaaca cggaaaccga agaccattca tgttgttgct caggtcgcag 3180
acgttttgca gcagcagtcg cttcacgttc gctcgcgtat cggtgattca ttctgctaac 3240
cagtaaggca accccgccag cctagccggg tcctcaacga caggagcacg atcatgcgca 3300
cccgtggggc cgccatgccg gcgataatgg cctgcttctc gccgaaacgt ttggtggcgg 3360
gaccagtgac gaaggcttga gcgagggcgt gcaagattcc gaataccgca agcgacaggc 3420
cgatcatcgt cgcgctccag cgaaagcggt cctcgccgaa aatgacccag agcgctgccg 3480
gcacctgtcc tacgagttgc atgataaaga agacagtcat aagtgcggcg acgatagtca 3540
tgccccgcgc ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag 3600
atcccggtgc ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt 3660
tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag 3720
gcggtttgcg tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc 3780
tgattgccct tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc 3840
cccagcaggc gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct 3900
tcggtatcgt cgtatcccac taccgagata tccgcaccaa cgcgcagccc ggactcggta 3960
atggcgcgca ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg 4020
atgccctcat tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct 4080
tcccgttccg ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga 4140
cgcagacgcg ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc 4200
aatgcgacca gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg 4260
ttgatgggtg tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct 4320
tccacagcaa tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt 4380
tgcgcgagaa gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc 4440
gacaccacca cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc 4500
gacggcgcgt gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc 4560
gccagttgtt gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact 4620
ttttcccgcg ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga 4680
taagagacac cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc 4740
ctgaattgac tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg 4800
atggtgtccg ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag 4860
tagtaggttg aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc 4920
gcccaacagt cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat 4980
gagcccgaag tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc 5040
aaccgcacct gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat 5100
ctcgatcccg cgaaattaat acgactcact ataggggaat tgtgagcgga taacaattcc 5160
cctctagaaa taattttgtt taactttaag aaggagatat acatatgacc tatactgttg 5220
gcatgtatct tgcagaacgc cttgtacaga tcgggctgaa gcatcacttc gccgtggcgg 5280
gcgactacaa tctcgttctt ctggatcagt tgctcctcaa caaggacatg aaacagatct 5340
attgctgcaa tgagttgaac tgtggcttca gcgcggaagg ctacgcccgt tctaacgggg 5400
ctgcggcagc ggttgtcacc ttcagcgttg gcgccatttc cgccatgaac gccctcggcg 5460
gcgcctatgc cgaaaacctg ccggttatcc tgatttccgg cgcgcccaac agcaatgatc 5520
agggcacagg tcatatcctg catcacacaa tcggcaagac ggattacagc taccagcttg 5580
aaatggcccg tcaggtcacc tgtgccgccg aaagcattac cgacgctcac tccgccccgg 5640
ccaagattga ccacgtcatt cgcacggcgc tgcgcgagcg taagccggcc tatctggaca 5700
tcgcgtgcaa cattgcctcc gagccctgcg tgcggcctgg ccctgtcagc agcctgctgt 5760
ccgagcctga aatcgaccac acgagcctga aggccgcagt ggacgccacg gttgccttgc 5820
tggaaaaatc ggccagcccc gtcatgctgc tgggcagcaa gctgcgggcc gccaacgcac 5880
tggccgcaac cgaaacgctg gcagacaagc tgcaatgcgc ggtgaccatc atggcggccg 5940
cgaaaggctt tttccccgaa gaccacgcgg gtttccgcgg cctgtactgg ggcgaagtct 6000
cgaaccccgg cgtgcaggaa ctggtggaga cctccgacgc actgctgtgc atcgcccccg 6060
tattcaacga ctattcaaca gtcggctggt cggcatggcc caagggcccc aatgtgattc 6120
tggctgagcc cgaccgcgta acggtcgatg gccgcgccta tgacggcttt accctgcgcg 6180
ccttcctgca ggctctggcg gaaaaagccc ccgcgcgccc ggcctccgca cagaaaagca 6240
gcgtcccgac gtgctcgctc accgcgacat ccgatgaagc cggtctgacg aatgacgaaa 6300
tcgtccgtca tatcaacgcc ctgctgacat caaacacgac gctggtggca gaaaccggcg 6360
attcatggtt caatgccatg cgcatgaccc tgccgcgcgg tgcgcgcgtg gaactggaaa 6420
tgcagtgggg ccatatcggc tggtccgtgc cctccgcctt cggcaatgcc atgggctcgc 6480
aggaccgcca gcatgtggtg atggtaggcg atggctcctt ccagcttacc gcgcaggaag 6540
tggctcagat ggtgcgctac gaactgcccg tcattatctt tctgatcaac aaccgtggct 6600
atgtcggtgg catcgccatt catgacggcc cgtacaacta tatcaagaac tgggattacg 6660
ccggcctgat ggaagtcttc aacgccggag aaggccatgg acttggcctg aaagccacca 6720
ccccgaagga actgacagaa gccatcgcca gggcaaaagc caatacccgc ggcccgacgc 6780
tgatcgaatg ccagatcgac cgcacggact gcacggatat gctggttcaa tggggccgca 6840
aggttgcctc aaccaacgcg cgcaagacca ctctggccct cgagcaccac caccaccacc 6900
actgagatcc ggctgctaac aaagcccgaa aggaagctga gttggctgct gccaccgctg 6960
agcaataact agcataaccc cttggggcct ctaaacgggt cttgaggggt tttttgctga 7020
aaggaggaac tatatccgga t 7041
<210> 6
<211> 29
<212> DNA
<213> 人工
<220>
<223> 人工制备
<220>
<221> misc_feature
<222> (14)..(14)
<223> n是a、c、g或t
<400> 6
ccgtggctat gtcndtggca tcgccattc 29
<210> 7
<211> 29
<212> DNA
<213> 人工
<220>
<223> 人工制备
<220>
<221> misc_feature
<222> (16)..(16)
<223> n是a、c、g或t
<400> 7
gaatggcgat gccahngaca tagccacgg 29
<210> 8
<211> 1680
<212> DNA
<213> 人工
<220>
<223> 人工制备
<400> 8
atgacctata ctgttggcat gtatcttgca gaacgccttg tacagatcgg gctgaagcat 60
cacttcgccg tggcgggcga ctacaatctc gttcttctgg atcagttgct cctcaacaag 120
gacatgaaac agatctattg ctgcaatgag ttgaactgtg gcttcagcgc ggaaggctac 180
gcccgttcta acggggctgc ggcagcggtt gtcaccttca gcgttggcgc catttccgcc 240
atgaacgccc tcggcggcgc ctatgccgaa aacctgccgg ttatcctgat ttccggcgcg 300
cccaacagca atgatcaggg cacaggtcat atcctgcatc acacaatcgg caagacggat 360
tacagctacc agcttgaaat ggcccgtcag gtcacctgtg ccgccgaaag cattaccgac 420
gctcactccg ccccggccaa gattgaccac gtcattcgca cggcgctgcg cgagcgtaag 480
ccggcctatc tggacatcgc gtgcaacatt gcctccgagc cctgcgtgcg gcctggccct 540
gtcagcagcc tgctgtccga gcctgaaatc gaccacacga gcctgaaggc cgcagtggac 600
gccacggttg ccttgctgga aaaatcggcc agccccgtca tgctgctggg cagcaagctg 660
cgggccgcca acgcactggc cgcaaccgaa acgctggcag acaagctgca atgcgcggtg 720
accatcatgg cggccgcgaa aggctttttc cccgaagacc acgcgggttt ccgcggcctg 780
tactggggcg aagtctcgaa ccccggcgtg caggaactgg tggagacctc cgacgcactg 840
ctgtgcatcg cccccgtatt caacgactat tcaacagtcg gctggtcggc atggcccaag 900
ggccccaatg tgattctggc tgagcccgac cgcgtaacgg tcgatggccg cgcctatgac 960
ggctttaccc tgcgcgcctt cctgcaggct ctggcggaaa aagcccccgc gcgcccggcc 1020
tccgcacaga aaagcagcgt cccgacgtgc tcgctcaccg cgacatccga tgaagccggt 1080
ctgacgaatg acgaaatcgt ccgtcatatc aacgccctgc tgacatcaaa cacgacgctg 1140
gtggcagaaa ccggcgattc atggttcaat gccatgcgca tgaccctgcc gcgcggtgcg 1200
cgcgtggaac tggaaatgca gtggggccat atcggctggt ccgtgccctc cgccttcggc 1260
aatgccatgg gctcgcagga ccgccagcat gtggtgatgg taggcgatgg ctccttccag 1320
cttaccgcgc aggaagtggc tcagatggtg cgctacgaac tgcccgtcat tatctttctg 1380
atcaacaacc gtggctatgt cattggcatc gccattcatg acggcccgta caactatatc 1440
aagaactggg attacgccgg cctgatggaa gtcttcaacg ccggagaagg ccatggactt 1500
ggcctgaaag ccaccacccc gaaggaactg acagaagcca tcgccagggc aaaagccaat 1560
acccgcggcc cgacgctgat cgaatgccag atcgaccgca cggactgcac ggatatgctg 1620
gttcaatggg gccgcaaggt tgcctcaacc aacgcgcgca agaccactct ggccctcgag 1680
<210> 9
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 9
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln His Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 10
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 10
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Phe Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 11
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 11
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Pro Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 12
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 12
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ile Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 13
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 13
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Leu Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 14
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 14
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Met Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 15
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 15
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Val Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 16
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 16
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ala Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 17
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 17
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Tyr Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 18
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 18
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Thr Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 19
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 19
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Gly Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 20
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 20
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ser Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 21
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 21
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Gly Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Cys Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 22
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 22
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln His Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 23
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 23
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Phe Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 24
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 24
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Pro Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 25
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 25
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ile Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 26
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 26
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Leu Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 27
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 27
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Met Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 28
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 28
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Val Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 29
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 29
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ala Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 30
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 30
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Tyr Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 31
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 31
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Thr Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 32
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 32
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Gly Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 33
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 33
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ser Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 34
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 34
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ala Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Cys Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 35
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 35
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln His Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 36
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 36
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Phe Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 37
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 37
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Pro Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 38
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 38
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ile Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 39
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 39
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Leu Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 40
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 40
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Met Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 41
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 41
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Val Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 42
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 42
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ala Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 43
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 43
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Tyr Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 44
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 44
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Thr Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 45
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 45
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Gly Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 46
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 46
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Ser Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 47
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 47
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Val Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Cys Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560
<210> 48
<211> 1680
<212> DNA
<213> 人工
<220>
<223> 人工制备
<400> 48
atgacctata ctgttggcat gtatcttgca gaacgccttg tacagatcgg gctgaagcat 60
cacttcgccg tggcgggcga ctacaatctc gttcttctgg atcagttgct cctcaacaag 120
gacatgaaac agatctattg ctgcaatgag ttgaactgtg gcttcagcgc ggaaggctac 180
gcccgttcta acggggctgc ggcagcggtt gtcaccttca gcgttggcgc catttccgcc 240
atgaacgccc tcggcggcgc ctatgccgaa aacctgccgg ttatcctgat ttccggcgcg 300
cccaacagca atgatcaggg cacaggtcat atcctgcatc acacaatcgg caagacggat 360
tacagctacc agcttgaaat ggcccgtcag gtcacctgtg ccgccgaaag cattaccgac 420
gctcactccg ccccggccaa gattgaccac gtcattcgca cggcgctgcg cgagcgtaag 480
ccggcctatc tggacatcgc gtgcaacatt gcctccgagc cctgcgtgcg gcctggccct 540
gtcagcagcc tgctgtccga gcctgaaatc gaccacacga gcctgaaggc cgcagtggac 600
gccacggttg ccttgctgga aaaatcggcc agccccgtca tgctgctggg cagcaagctg 660
cgggccgcca acgcactggc cgcaaccgaa acgctggcag acaagctgca atgcgcggtg 720
accatcatgg cggccgcgaa aggctttttc cccgaagacc acgcgggttt ccgcggcctg 780
tactggggcg aagtctcgaa ccccggcgtg caggaactgg tggagacctc cgacgcactg 840
ctgtgcatcg cccccgtatt caacgactat tcaacagtcg gctggtcggc atggcccaag 900
ggccccaatg tgattctggc tgagcccgac cgcgtaacgg tcgatggccg cgcctatgac 960
ggctttaccc tgcgcgcctt cctgcaggct ctggcggaaa aagcccccgc gcgcccggcc 1020
tccgcacaga aaagcagcgt cccgacgtgc tcgctcaccg cgacatccga tgaagccggt 1080
ctgacgaatg acgaaatcgt ccgtcatatc aacgccctgc tgacatcaaa cacgacgctg 1140
gtggcagaaa ccggcgattc atggttcaat gccatgcgca tgaccctgcc gcgcggtgcg 1200
cgcgtggaac tggaaatgca gtggggccat atcggctggt ccgtgccctc cgccttcggc 1260
aatgccatgg gctcgcagga ccgccagcat gtggtgatgg taggcgatgg ctccttccag 1320
cttaccgcgc aggaagtggc tcagatggtg cgctacgaac tgcccgtcat tatctttctg 1380
atcaacaacc gtggctatgt cgccggcatc gccattcatg acggcccgta caactatatc 1440
aagaactggg attacgccgg cctgatggaa gtcttcaacg ccggagaagg ccatggactt 1500
ggcctgaaag ccaccacccc gaaggaactg acagaagcca tcgccagggc aaaagccaat 1560
acccgcggcc cgacgctgat cgaatgccag atcgaccgca cggactgcac ggatatgctg 1620
gttcaatttg gccgcaaggt tgcctcaacc aacgcgcgca agaccactct ggccctcgag 1680
<210> 49
<211> 7041
<212> DNA
<213> 人工
<220>
<223> 人工制备
<400> 49
tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60
cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120
ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180
gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240
acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300
ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360
ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420
acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480
tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540
tccgctcatg agacaataac cctgataaat gcttcaataa tattgaaaaa ggaagagtat 600
gagtattcaa catttccgtg tcgcccttat tccctttttt gcggcatttt gccttcctgt 660
ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct gaagatcagt tgggtgcacg 720
agtgggttac atcgaactgg atctcaacag cggtaagatc cttgagagtt ttcgccccga 780
agaacgtttt ccaatgatga gcacttttaa agttctgcta tgtggcgcgg tattatcccg 840
tattgacgcc gggcaagagc aactcggtcg ccgcatacac tattctcaga atgacttggt 900
tgagtactca ccagtcacag aaaagcatct tacggatggc atgacagtaa gagaattatg 960
cagtgctgcc ataaccatga gtgataacac tgcggccaac ttacttctga caacgatcgg 1020
aggaccgaag gagctaaccg cttttttgca caacatgggg gatcatgtaa ctcgccttga 1080
tcgttgggaa ccggagctga atgaagccat accaaacgac gagcgtgaca ccacgatgcc 1140
tgcagcaatg gcaacaacgt tgcgcaaact attaactggc gaactactta ctctagcttc 1200
ccggcaacaa ttaatagact ggatggaggc ggataaagtt gcaggaccac ttctgcgctc 1260
ggcccttccg gctggctggt ttattgctga taaatctgga gccggtgagc gtgggtctcg 1320
cggtatcatt gcagcactgg ggccagatgg taagccctcc cgtatcgtag ttatctacac 1380
gacggggagt caggcaacta tggatgaacg aaatagacag atcgctgaga taggtgcctc 1440
actgattaag cattggtaac tgtcagacca agtttactca tatatacttt agattgattt 1500
aaaacttcat ttttaattta aaaggatcta ggtgaagatc ctttttgata atctcatgac 1560
caaaatccct taacgtgagt tttcgttcca ctgagcgtca gaccccgtag aaaagatcaa 1620
aggatcttct tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa caaaaaaacc 1680
accgctacca gcggtggttt gtttgccgga tcaagagcta ccaactcttt ttccgaaggt 1740
aactggcttc agcagagcgc agataccaaa tactgtcctt ctagtgtagc cgtagttagg 1800
ccaccacttc aagaactctg tagcaccgcc tacatacctc gctctgctaa tcctgttacc 1860
agtggctgct gccagtggcg ataagtcgtg tcttaccggg ttggactcaa gacgatagtt 1920
accggataag gcgcagcggt cgggctgaac ggggggttcg tgcacacagc ccagcttgga 1980
gcgaacgacc tacaccgaac tgagatacct acagcgtgag ctatgagaaa gcgccacgct 2040
tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa caggagagcg 2100
cacgagggag cttccagggg gaaacgcctg gtatctttat agtcctgtcg ggtttcgcca 2160
cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc tatggaaaaa 2220
cgccagcaac gcggcctttt tacggttcct ggccttttgc tggccttttg ctcacatgtt 2280
ctttcctgcg ttatcccctg attctgtgga taaccgtatt accgcctttg agtgagctga 2340
taccgctcgc cgcagccgaa cgaccgagcg cagcgagtca gtgagcgagg aagcggaaga 2400
gcgcctgatg cggtattttc tccttacgca tctgtgcggt atttcacacc gcatatatgg 2460
tgcactctca gtacaatctg ctctgatgcc gcatagttaa gccagtatac actccgctat 2520
cgctacgtga ctgggtcatg gctgcgcccc gacacccgcc aacacccgct gacgcgccct 2580
gacgggcttg tctgctcccg gcatccgctt acagacaagc tgtgaccgtc tccgggagct 2640
gcatgtgtca gaggttttca ccgtcatcac cgaaacgcgc gaggcagctg cggtaaagct 2700
catcagcgtg gtcgtgaagc gattcacaga tgtctgcctg ttcatccgcg tccagctcgt 2760
tgagtttctc cagaagcgtt aatgtctggc ttctgataaa gcgggccatg ttaagggcgg 2820
ttttttcctg tttggtcact gatgcctccg tgtaaggggg atttctgttc atgggggtaa 2880
tgataccgat gaaacgagag aggatgctca cgatacgggt tactgatgat gaacatgccc 2940
ggttactgga acgttgtgag ggtaaacaac tggcggtatg gatgcggcgg gaccagagaa 3000
aaatcactca gggtcaatgc cagcgcttcg ttaatacaga tgtaggtgtt ccacagggta 3060
gccagcagca tcctgcgatg cagatccgga acataatggt gcagggcgct gacttccgcg 3120
tttccagact ttacgaaaca cggaaaccga agaccattca tgttgttgct caggtcgcag 3180
acgttttgca gcagcagtcg cttcacgttc gctcgcgtat cggtgattca ttctgctaac 3240
cagtaaggca accccgccag cctagccggg tcctcaacga caggagcacg atcatgcgca 3300
cccgtggggc cgccatgccg gcgataatgg cctgcttctc gccgaaacgt ttggtggcgg 3360
gaccagtgac gaaggcttga gcgagggcgt gcaagattcc gaataccgca agcgacaggc 3420
cgatcatcgt cgcgctccag cgaaagcggt cctcgccgaa aatgacccag agcgctgccg 3480
gcacctgtcc tacgagttgc atgataaaga agacagtcat aagtgcggcg acgatagtca 3540
tgccccgcgc ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag 3600
atcccggtgc ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt 3660
tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag 3720
gcggtttgcg tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc 3780
tgattgccct tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc 3840
cccagcaggc gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct 3900
tcggtatcgt cgtatcccac taccgagata tccgcaccaa cgcgcagccc ggactcggta 3960
atggcgcgca ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg 4020
atgccctcat tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct 4080
tcccgttccg ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga 4140
cgcagacgcg ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc 4200
aatgcgacca gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg 4260
ttgatgggtg tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct 4320
tccacagcaa tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt 4380
tgcgcgagaa gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc 4440
gacaccacca cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc 4500
gacggcgcgt gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc 4560
gccagttgtt gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact 4620
ttttcccgcg ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga 4680
taagagacac cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc 4740
ctgaattgac tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg 4800
atggtgtccg ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag 4860
tagtaggttg aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc 4920
gcccaacagt cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat 4980
gagcccgaag tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc 5040
aaccgcacct gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat 5100
ctcgatcccg cgaaattaat acgactcact ataggggaat tgtgagcgga taacaattcc 5160
cctctagaaa taattttgtt taactttaag aaggagatat acatatgacc tatactgttg 5220
gcatgtatct tgcagaacgc cttgtacaga tcgggctgaa gcatcacttc gccgtggcgg 5280
gcgactacaa tctcgttctt ctggatcagt tgctcctcaa caaggacatg aaacagatct 5340
attgctgcaa tgagttgaac tgtggcttca gcgcggaagg ctacgcccgt tctaacgggg 5400
ctgcggcagc ggttgtcacc ttcagcgttg gcgccatttc cgccatgaac gccctcggcg 5460
gcgcctatgc cgaaaacctg ccggttatcc tgatttccgg cgcgcccaac agcaatgatc 5520
agggcacagg tcatatcctg catcacacaa tcggcaagac ggattacagc taccagcttg 5580
aaatggcccg tcaggtcacc tgtgccgccg aaagcattac cgacgctcac tccgccccgg 5640
ccaagattga ccacgtcatt cgcacggcgc tgcgcgagcg taagccggcc tatctggaca 5700
tcgcgtgcaa cattgcctcc gagccctgcg tgcggcctgg ccctgtcagc agcctgctgt 5760
ccgagcctga aatcgaccac acgagcctga aggccgcagt ggacgccacg gttgccttgc 5820
tggaaaaatc ggccagcccc gtcatgctgc tgggcagcaa gctgcgggcc gccaacgcac 5880
tggccgcaac cgaaacgctg gcagacaagc tgcaatgcgc ggtgaccatc atggcggccg 5940
cgaaaggctt tttccccgaa gaccacgcgg gtttccgcgg cctgtactgg ggcgaagtct 6000
cgaaccccgg cgtgcaggaa ctggtggaga cctccgacgc actgctgtgc atcgcccccg 6060
tattcaacga ctattcaaca gtcggctggt cggcatggcc caagggcccc aatgtgattc 6120
tggctgagcc cgaccgcgta acggtcgatg gccgcgccta tgacggcttt accctgcgcg 6180
ccttcctgca ggctctggcg gaaaaagccc ccgcgcgccc ggcctccgca cagaaaagca 6240
gcgtcccgac gtgctcgctc accgcgacat ccgatgaagc cggtctgacg aatgacgaaa 6300
tcgtccgtca tatcaacgcc ctgctgacat caaacacgac gctggtggca gaaaccggcg 6360
attcatggtt caatgccatg cgcatgaccc tgccgcgcgg tgcgcgcgtg gaactggaaa 6420
tgcagtgggg ccatatcggc tggtccgtgc cctccgcctt cggcaatgcc atgggctcgc 6480
aggaccgcca gcatgtggtg atggtaggcg atggctcctt ccagcttacc gcgcaggaag 6540
tggctcagat ggtgcgctac gaactgcccg tcattatctt tctgatcaac aaccgtggct 6600
atgtcgccgg catcgccatt catgacggcc cgtacaacta tatcaagaac tgggattacg 6660
ccggcctgat ggaagtcttc aacgccggag aaggccatgg acttggcctg aaagccacca 6720
ccccgaagga actgacagaa gccatcgcca gggcaaaagc caatacccgc ggcccgacgc 6780
tgatcgaatg ccagatcgac cgcacggact gcacggatat gctggttcaa tttggccgca 6840
aggttgcctc aaccaacgcg cgcaagacca ctctggccct cgagcaccac caccaccacc 6900
actgagatcc ggctgctaac aaagcccgaa aggaagctga gttggctgct gccaccgctg 6960
agcaataact agcataaccc cttggggcct ctaaacgggt cttgaggggt tttttgctga 7020
aaggaggaac tatatccgga t 7041
<210> 50
<211> 34
<212> DNA
<213> 人工
<220>
<223> 人工制备
<400> 50
accttgcggc cgaattgaac cagcatatcc gtgc 34
<210> 51
<211> 34
<212> DNA
<213> 人工
<220>
<223> 人工制备
<400> 51
gcacggatat gctggttcaa ttcggccgca aggt 34
<210> 52
<211> 1680
<212> DNA
<213> 人工
<220>
<223> 人工制备
<400> 52
atgacctata ctgttggcat gtatcttgca gaacgccttg tacagatcgg gctgaagcat 60
cacttcgccg tggcgggcga ctacaatctc gttcttctgg atcagttgct cctcaacaag 120
gacatgaaac agatctattg ctgcaatgag ttgaactgtg gcttcagcgc ggaaggctac 180
gcccgttcta acggggctgc ggcagcggtt gtcaccttca gcgttggcgc catttccgcc 240
atgaacgccc tcggcggcgc ctatgccgaa aacctgccgg ttatcctgat ttccggcgcg 300
cccaacagca atgatcaggg cacaggtcat atcctgcatc acacaatcgg caagacggat 360
tacagctacc agcttgaaat ggcccgtcag gtcacctgtg ccgccgaaag cattaccgac 420
gctcactccg ccccggccaa gattgaccac gtcattcgca cggcgctgcg cgagcgtaag 480
ccggcctatc tggacatcgc gtgcaacatt gcctccgagc cctgcgtgcg gcctggccct 540
gtcagcagcc tgctgtccga gcctgaaatc gaccacacga gcctgaaggc cgcagtggac 600
gccacggttg ccttgctgga aaaatcggcc agccccgtca tgctgctggg cagcaagctg 660
cgggccgcca acgcactggc cgcaaccgaa acgctggcag acaagctgca atgcgcggtg 720
accatcatgg cggccgcgaa aggctttttc cccgaagacc acgcgggttt ccgcggcctg 780
tactggggcg aagtctcgaa ccccggcgtg caggaactgg tggagacctc cgacgcactg 840
ctgtgcatcg cccccgtatt caacgactat tcaacagtcg gctggtcggc atggcccaag 900
ggccccaatg tgattctggc tgagcccgac cgcgtaacgg tcgatggccg cgcctatgac 960
ggctttaccc tgcgcgcctt cctgcaggct ctggcggaaa aagcccccgc gcgcccggcc 1020
tccgcacaga aaagcagcgt cccgacgtgc tcgctcaccg cgacatccga tgaagccggt 1080
ctgacgaatg acgaaatcgt ccgtcatatc aacgccctgc tgacatcaaa cacgacgctg 1140
gtggcagaaa ccggcgattc atggttcaat gccatgcgca tgaccctgcc gcgcggtgcg 1200
cgcgtggaac tggaaatgca gtggggccat atcggctggt ccgtgccctc cgccttcggc 1260
aatgccatgg gctcgcagga ccgccagcat gtggtgatgg taggcgatgg ctccttccag 1320
cttaccgcgc aggaagtggc tcagatggtg cgctacgaac tgcccgtcat tatctttctg 1380
atcaacaacc gtggctatgt cgccggcatc gccattcatg acggcccgta caactatatc 1440
aagaactggg attacgccgg cctgatggaa gtcttcaacg ccggagaagg ccatggactt 1500
ggcctgaaag ccaccacccc gaaggaactg acagaagcca tcgccagggc aaaagccaat 1560
acccgcggcc cgacgctgat cgaatgccag atcgaccgca cggactgcac ggatatgctg 1620
gttcaatggg gccgcaaggt tgcctcaacc aacgcgcgca agaccactct ggccctcgag 1680
<210> 53
<211> 560
<212> PRT
<213> 人工
<220>
<223> 人工制备
<400> 53
Met Thr Tyr Thr Val Gly Met Tyr Leu Ala Glu Arg Leu Val Gln Ile
1 5 10 15
Gly Leu Lys His His Phe Ala Val Ala Gly Asp Tyr Asn Leu Val Leu
20 25 30
Leu Asp Gln Leu Leu Leu Asn Lys Asp Met Lys Gln Ile Tyr Cys Cys
35 40 45
Asn Glu Leu Asn Cys Gly Phe Ser Ala Glu Gly Tyr Ala Arg Ser Asn
50 55 60
Gly Ala Ala Ala Ala Val Val Thr Phe Ser Val Gly Ala Ile Ser Ala
65 70 75 80
Met Asn Ala Leu Gly Gly Ala Tyr Ala Glu Asn Leu Pro Val Ile Leu
85 90 95
Ile Ser Gly Ala Pro Asn Ser Asn Asp Gln Gly Thr Gly His Ile Leu
100 105 110
His His Thr Ile Gly Lys Thr Asp Tyr Ser Tyr Gln Leu Glu Met Ala
115 120 125
Arg Gln Val Thr Cys Ala Ala Glu Ser Ile Thr Asp Ala His Ser Ala
130 135 140
Pro Ala Lys Ile Asp His Val Ile Arg Thr Ala Leu Arg Glu Arg Lys
145 150 155 160
Pro Ala Tyr Leu Asp Ile Ala Cys Asn Ile Ala Ser Glu Pro Cys Val
165 170 175
Arg Pro Gly Pro Val Ser Ser Leu Leu Ser Glu Pro Glu Ile Asp His
180 185 190
Thr Ser Leu Lys Ala Ala Val Asp Ala Thr Val Ala Leu Leu Glu Lys
195 200 205
Ser Ala Ser Pro Val Met Leu Leu Gly Ser Lys Leu Arg Ala Ala Asn
210 215 220
Ala Leu Ala Ala Thr Glu Thr Leu Ala Asp Lys Leu Gln Cys Ala Val
225 230 235 240
Thr Ile Met Ala Ala Ala Lys Gly Phe Phe Pro Glu Asp His Ala Gly
245 250 255
Phe Arg Gly Leu Tyr Trp Gly Glu Val Ser Asn Pro Gly Val Gln Glu
260 265 270
Leu Val Glu Thr Ser Asp Ala Leu Leu Cys Ile Ala Pro Val Phe Asn
275 280 285
Asp Tyr Ser Thr Val Gly Trp Ser Ala Trp Pro Lys Gly Pro Asn Val
290 295 300
Ile Leu Ala Glu Pro Asp Arg Val Thr Val Asp Gly Arg Ala Tyr Asp
305 310 315 320
Gly Phe Thr Leu Arg Ala Phe Leu Gln Ala Leu Ala Glu Lys Ala Pro
325 330 335
Ala Arg Pro Ala Ser Ala Gln Lys Ser Ser Val Pro Thr Cys Ser Leu
340 345 350
Thr Ala Thr Ser Asp Glu Ala Gly Leu Thr Asn Asp Glu Ile Val Arg
355 360 365
His Ile Asn Ala Leu Leu Thr Ser Asn Thr Thr Leu Val Ala Glu Thr
370 375 380
Gly Asp Ser Trp Phe Asn Ala Met Arg Met Thr Leu Pro Arg Gly Ala
385 390 395 400
Arg Val Glu Leu Glu Met Gln Trp Gly His Ile Gly Trp Ser Val Pro
405 410 415
Ser Ala Phe Gly Asn Ala Met Gly Ser Gln Asp Arg Gln His Val Val
420 425 430
Met Val Gly Asp Gly Ser Phe Gln Leu Thr Ala Gln Glu Val Ala Gln
435 440 445
Met Val Arg Tyr Glu Leu Pro Val Ile Ile Phe Leu Ile Asn Asn Arg
450 455 460
Gly Tyr Val Ile Gly Ile Ala Ile His Asp Gly Pro Tyr Asn Tyr Ile
465 470 475 480
Lys Asn Trp Asp Tyr Ala Gly Leu Met Glu Val Phe Asn Ala Gly Glu
485 490 495
Gly His Gly Leu Gly Leu Lys Ala Thr Thr Pro Lys Glu Leu Thr Glu
500 505 510
Ala Ile Ala Arg Ala Lys Ala Asn Thr Arg Gly Pro Thr Leu Ile Glu
515 520 525
Cys Gln Ile Asp Arg Thr Asp Cys Thr Asp Met Leu Val Gln Trp Gly
530 535 540
Arg Lys Val Ala Ser Thr Asn Ala Arg Lys Thr Thr Leu Ala Leu Glu
545 550 555 560

Claims (18)

1.裂解酶，
其中在相对于巴氏醋杆菌野生型修饰的蛋白ApPDC-E469G中在位置号468中的氨基酸异亮氨酸被比异亮氨酸较不占空间的氨基酸置换，
其特征在于，
其具有根据SEQ ID NO:1、SEQ ID NO:2或SEQ ID NO:3之一的氨基酸序列。
2.根据权利要求1的裂解酶，
其特征在于，
其具有根据SEQ ID NO:23的氨基酸序列。
3.编码根据权利要求1的裂解酶的脱氧核糖核酸，
其特征在于，
其具有根据SEQ ID NO:4的核苷酸序列。
4.编码根据权利要求2的裂解酶的脱氧核糖核酸，
其特征在于，
其具有根据SEQ ID NO:48的核苷酸序列。
5.载体，
其特征在于，
其包含根据SEQ ID NO:4或SEQ ID NO:48的脱氧核糖核酸。
6.根据权利要求5的载体，
其特征在于，
其是质粒。
7.根据权利要求6的载体，
其特征在于，
根据权利要求3或4限定的核苷酸序列连接在选自pET-20b(+)、pET-21a-d(+)、pET-22b(+)、pET-23a-d(+)、pET-24a-d(+)、pET-25b(+)、pET-26b(+)、pET-27b(+)、pET-28a(+)、pET-29a-c(+)、pET-30a-c(+)、pET-31b(+)、pET-34b(+)、pET-35b(+)、pET-36b(+)、pET-37b(+)、pET-38b(+)的空载体中。
8.用于制备(S)-苯基乙酰基甲醇的方法，其中使苯甲醛与丙酮酸或与乙醛根据式(1)反应，
式(1)
Figure 803707DEST_PATH_IMAGE001
其特征在于，
所述反应通过根据权利要求1或2的裂解酶进行。
9.根据权利要求8的方法，
其特征在于，
其在5 - 9的pH值下进行。
10.根据权利要求8或9的方法，
其特征在于，
使用HEPES、MOPS、TEA或TRIS-HCl作为缓冲液。
11.根据权利要求8至10任一项的方法，
其特征在于，
使用磷酸硫胺素和硫酸镁作为辅因子。
12.根据权利要求8至11任一项的方法，
其特征在于，
所述反应在体内进行。
13.根据权利要求12的方法，
其特征在于，
(S)-苯基乙酰基甲醇的生产在选自大肠杆菌，棒状杆菌，谷氨酸棒状杆菌，或酵母，酿酒酵母的生产生物体中进行。
14.根据权利要求13的方法，
其特征在于，
所述生物体用SEQ ID NO:4或SEQ ID NO:48的DNA的至少一种进行转化和/或将根据SEQ ID NO:4或SEQ ID NO:48的DNA整合到基因组中。
15.根据权利要求14的方法，
其特征在于，
对于所述转化使用根据权利要求5至7中任一项的载体。
16.根据权利要求8至11任一项的方法，
其特征在于，
所述反应在体外进行。
17.根据权利要求16的方法，
其特征在于，
使用根据SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3或SEQ ID NO:23的分离的酶。
18.根据权利要求16的方法，
其特征在于，
使用来自生产生物体的粗细胞提取物。
CN201580049895.0A 2014-09-16 2015-08-27 裂解酶以及不对称合成(s)-苯基乙酰基甲醇的方法 Active CN106715689B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE102014013642.6 2014-09-16
DE102014013642.6A DE102014013642A1 (de) 2014-09-16 2014-09-16 Lyase sowie Verfahren zur asymmetrischen Synthese von (S)-Phenylacetylcarbinol
PCT/DE2015/000435 WO2016041535A1 (de) 2014-09-16 2015-08-27 Lyase sowie verfahren zur asymmetrischen synthese von (s)-phenylacetylcarbinol

Publications (2)

Publication Number Publication Date
CN106715689A CN106715689A (zh) 2017-05-24
CN106715689B true CN106715689B (zh) 2020-09-25

Family

ID=54251901

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201580049895.0A Active CN106715689B (zh) 2014-09-16 2015-08-27 裂解酶以及不对称合成(s)-苯基乙酰基甲醇的方法

Country Status (7)

Country Link
US (1) US10465211B2 (zh)
EP (1) EP3194588B1 (zh)
JP (1) JP6752207B2 (zh)
CN (1) CN106715689B (zh)
DE (1) DE102014013642A1 (zh)
ES (1) ES2833463T3 (zh)
WO (1) WO2016041535A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102017210944B4 (de) 2017-06-28 2019-05-23 Technische Universität Dresden Alkoholdehydrogenasen und Verfahren zur stereoselektiven Reduktion von Carbonylverbindungen

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101608191A (zh) * 2009-07-09 2009-12-23 上海交通大学 L-苯基乙酰基甲醇的制备方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5789166A (en) 1995-12-08 1998-08-04 Stratagene Circular site-directed mutagenesis
DE102014013644A1 (de) * 2014-09-16 2016-03-17 Forschungszentrum Jülich GmbH Lyase und für die Lyase kodierende DNA, die DNA enthaltende Vektoren, sowie Verfahren zur asymmetrischen Synthese von (S)-Phenylacetylcarbinol

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101608191A (zh) * 2009-07-09 2009-12-23 上海交通大学 L-苯基乙酰基甲醇的制备方法
CN101608191B (zh) * 2009-07-09 2011-08-31 上海交通大学 L-苯基乙酰基甲醇的制备方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
A Tailor-Made Chimeric Thiamine Diphosphate Dependent Enzyme for the Direct Asymmetric Synthesis of (S)-Benzoins;Robert Westphal等;《Angewandte chemie》;20140825;第53卷(第35期);第9376-9379页 *
Engineering stereoselectivity of ThDP-dependent enzymes;Helen C.Hailes等;《FEBS Journal》;20130913;第280卷;第6374-6394页 *
S-Selective Mixed Carboligation by Structure-Based Design of the Pyruvate Decarboxylase from Acetobacter pasteurianus;Dçrte Rother等;《ChemCatChem》;20110831;第3卷(第10期);第1587-1596页 *

Also Published As

Publication number Publication date
US10465211B2 (en) 2019-11-05
CN106715689A (zh) 2017-05-24
ES2833463T3 (es) 2021-06-15
EP3194588A1 (de) 2017-07-26
DE102014013642A1 (de) 2016-03-17
JP6752207B2 (ja) 2020-09-09
EP3194588B1 (de) 2020-10-21
JP2017527312A (ja) 2017-09-21
WO2016041535A1 (de) 2016-03-24
US20170260550A1 (en) 2017-09-14

Similar Documents

Publication Publication Date Title
CN110923183A (zh) 产羊毛甾醇大肠杆菌菌株的构建方法
CN111893104B (zh) 一种基于结构的crispr蛋白的优化设计方法
CN112553176B (zh) 一种热稳定性提高的谷氨酰胺转氨酶
CN110229838A (zh) 一种生物转化类固醇类化合物获取羟基化化合物的方法
CN106755031B (zh) 鼠李糖脂生产质粒及其构建方法与大肠杆菌工程菌和应用
CN106715689B (zh) 裂解酶以及不对称合成(s)-苯基乙酰基甲醇的方法
CN107075495B (zh) 裂解酶和编码该裂解酶的dna、含该dna的载体以及用于不对称合成(s)-苯基乙酰基甲醇的方法
CN114426957B (zh) 一种糖醛酸脱氢酶突变体及其在制备糖二酸中的应用
CN109402109B (zh) 一种改进的重叠延伸pcr方法
CN110964702B (zh) 一种Diels-Alder反应酶的应用及其突变体的制备方法与应用
RU2792132C1 (ru) Рекомбинантная плазмида pET-GST-3CL, обеспечивающая синтез протеазы 3CL SARS-CoV-2 в клетках E.coli в растворимой форме
RU2774333C1 (ru) Рекомбинантная плазмида pET-GST-3CL-GPG, обеспечивающая синтез протеазы 3CL SARS-CoV-2 в клетках E.coli в растворимой форме
CN111748034B (zh) 一种滑液囊支原体单克隆抗体的制备方法
KR20130135722A (ko) 광 유도성 프로모터 및 이를 포함하는 유전자 발현 시스템
CN113755512B (zh) 一种制备串联重复蛋白质的方法与应用
CN112553177B (zh) 一种热稳定性提高的谷氨酰胺转氨酶变体
CN114317473B (zh) 一种催化活性和热稳定性提高的谷氨酰胺转氨酶变体
CN113980883B (zh) 一种高产羟基化甾体原料药的重组大肠杆菌及其应用
CN113234746B (zh) 一种农药诱导蛋白互作和诱导基因表达的方法
KR100902634B1 (ko) 재조합 ｈｍｇｂ1 펩티드를 포함하는 핵산 전달 복합체
CN114539425B (zh) 一种提高线性多肽生物表达的方法
JP3012931B1 (ja) Ｓｐａｒｃ融合タンパク質およびその製造方法
KR101137021B1 (ko) 퓨조박테리움 뉴클레텀 유래의 신규 글리코실트랜스퍼라제및 이를 이용한 올리고당 제조방법
CN109666689B (zh) 一种重组高温镍铁氢化酶的异源表达纯化方法及其应用
KR101892358B1 (ko) 프롤리다아제 돌연변이체 및 이의 제조방법 및 이에 따라 제조된 프롤리다아제 돌연변이체의 용도

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant