CN107580503B - 用于治疗细菌感染的杀菌剂与亲溶酶体碱化剂的组合 - Google Patents

用于治疗细菌感染的杀菌剂与亲溶酶体碱化剂的组合 Download PDF

Info

Publication number
CN107580503B
CN107580503B CN201680026953.2A CN201680026953A CN107580503B CN 107580503 B CN107580503 B CN 107580503B CN 201680026953 A CN201680026953 A CN 201680026953A CN 107580503 B CN107580503 B CN 107580503B
Authority
CN
China
Prior art keywords
gly
lys
val
ala
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
CN201680026953.2A
Other languages
English (en)
Other versions
CN107580503A (zh
Inventor
弗里茨·艾兴泽埃尔
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.)
Micreos Human Health BV
Original Assignee
Micreos Human Health BV
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 Micreos Human Health BV filed Critical Micreos Human Health BV
Publication of CN107580503A publication Critical patent/CN107580503A/zh
Application granted granted Critical
Publication of CN107580503B publication Critical patent/CN107580503B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A61K31/431—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2462—Lysozyme (3.2.1.17)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明涉及医药领域，特别是涉及细菌感染及其治疗领域。

Description

用于治疗细菌感染的杀菌剂与亲溶酶体碱化剂的组合
技术领域
本发明涉及医药领域，特别是涉及细菌感染及其治疗领域。
背景技术
人类病原体金黄色葡萄球菌(Staphylococcus aureus)存在于约三分之一的全部人类中，并且是工业化世界中菌血症(bacteremia)和感染性心内膜炎的主要原因之一(1)。除了新出现的抗生素耐药性，持续和复发性感染显著地增加了发病率和死亡率(2,3)。特别是在骨髓炎或心内膜炎之后，复发率很高，并且在明显治愈后甚至几年内感染都可能复发(4)。感染复发出于几个缘由与SCV(small colony variant，小菌落变异体)和/或非复制性持留菌因子(non-replicating persister)有关(5-8)。它们受抑制的或缓慢的生长和降低的新陈代谢会使抗生素效率低下(9-13)。此外，它们优先隐藏于特殊位置(privilegedlocation)，例如脓肿和宿主细胞内(14-16)。这些特殊位置使其免受宿主的先天免疫系统和细胞外活性抗生素的侵害。此外，由于pH低，抗生素不能有效渗透脓肿并且活性较低(17-21)。因此，即使抗生素活性高，但是“有脓就挤(ubi pus ibi evacua)”—在古代制定的手术切除脓肿的必要性现在仍然适用。与脓肿相反，细胞内细菌不能机械去除，并且经常抵抗目前可获得的抗生素的根除。在诊所中分离出的大多数SCV在传代培养(sub-cultivation)后会恢复到大的集落表型。由于这些不稳定的性质，在电子传递系统中具有缺陷的稳定遗传改性的SCV突变体已经用于找寻靶向SCV的新策略，并据发现定位于宿主细胞溶酶体中(22)。然而，稳定的SCV仅部分反映临床SCV。它们毒性较低(23)，以及不能恢复到高毒性和快速生长的表型。因此，迫切需要研究临床SCV和持留菌的手段和最终的治疗SCV和持留菌(persister)的有效方法。
发明内容
令人惊奇的是，本发明人已经确定可逆的持留菌和可逆的SCV能够由低pH诱导，并且低pH适应细菌在细胞内，特别是在溶酶体(低pH细胞器)内持续存在。在pH升高时，低pH诱导的SCV和持留菌返回为所述高毒力表型。提高所述pH会细胞内返回体外和体内细菌适应的所述低pH，并使所述SCV和持留菌对通常在细胞内无效的抗菌剂敏感。这提供了一种预防和/或治疗主要或至少部分细胞内持留于细胞内区室中的感染，如但不限于皮肤感染，呼吸道或扁桃体上皮(咽炎)的感染，(牛)乳腺炎，或消除孕妇阴道无乳链球菌(S.agalactiae)感染(巨噬细胞内)以预防新生儿败血症或预防/治疗肺炎链球菌(S.pneumoniae)诱导的单核细胞衍生的巨噬细胞凋亡，或治疗结核病(tuberculosis)，麻风病(leprosy)，李斯特菌病(listeriosis)，伤寒症(typhoid fever)，杆菌性痢疾(bacillary dysenteria)，瘟疫(plague)，布鲁氏菌病(brucellosis)，斑疹伤寒(typhus)，落基山斑点热(RockyMountains spotted fever)，衣原体疾病(chlamydia)，沙眼(trachoma)的全新方法。
因此，在第一方面中，本发明提供了治疗需要其的受试者中的细菌感染的方法，包括：
-给予有效量的提高宿主细胞和/或宿主细胞的细胞内区室的细胞内pH的试剂，和
-给予有效量的杀菌剂。所述方法在本文中称为根据本发明的方法。
优选在本发明的实施方式中，pH的升高会激活非复制性细胞内细菌并且所述杀细菌剂会杀死所述活化的细胞内细菌。
在本发明的实施方式中，所述细菌感染优选是持留细菌感染，并且可能与各种组织，如但不限于皮肤，呼吸道上皮，扁桃体组织，乳腺炎的持留性金黄色葡萄球菌感染有关。在本发明的实施方式中，所述细菌感染优选是由选自由以下各项组成的细菌组中的物种引起的感染：葡萄球菌属，链球菌属(如化脓性链球菌(S.pyogenes)，无乳链球菌(S.agalactiae)和肺炎链球菌(S.pneumonia))，放线菌属，诺卡氏菌属，芽孢杆菌属(例如，炭疽杆菌(B.anthracis))，考克斯氏体属(Coxiella)(如贝纳特氏考克斯氏体(Coxiellaburnetii))，立克次体(Rickettsia)，分枝杆菌(如结核分枝杆菌(M.tuberculosis)和麻疯分支杆菌(M.leprae))，军团杆菌属(Legionella)(如嗜肺性军团杆菌(L.pneumophila))，支原体(Mycoplasma)，沙门氏菌属(如鼠伤寒沙门氏菌(S.typhimurium))，志贺氏杆菌(Shigella)(如痢疾志贺氏杆菌(S.dysenteriae))，耶尔森氏菌(Yersinia)(如鼠疫耶尔森氏菌(Y.pestis))，布鲁杆菌属(Brucella)，李斯特菌属(Listeria)(如单核细胞增生李斯特氏菌(L.monocytogenesis))，放线杆菌属(Actinobacillus)(如伴放线放线杆菌(A.actinomycetemcomitans))，加德纳菌(Gardnerella)(例如阴道加德纳菌(G.vaginalis))，衣原体(沙眼衣原体(C.trachomatis))和Chlamidophila；更优选的细菌是葡萄球菌的一个种；优选的葡萄球菌种是金黄色葡萄球菌。
在本发明的实施方式中，引起所述细菌感染的细菌优选胞内存在于宿主细胞中，如所述胞质溶胶中；更优选引起所述细菌感染的细菌优选存在于金黄色葡萄球菌的细胞内区室内。优选所述细菌感染包括包含至少一种对杀菌剂(例如，抗生素)，例如，但不限于MRSA具有抗药性的细菌亚群的细菌群体。在本发明的实施方式中，所述细胞内区室可以是任何细胞内区室，其中细菌能够持续存在和/或持续存在；优选所述细胞内区室是具有低pH值的区室。优选的细胞内区室是选自由内涵体(endosome)、溶酶体(lysozome)、吞噬体(phagosome)、吞噬溶酶体(phagolysosome)、自噬体(autophagosome)和自噬溶酶体(autolysosome)组成的组的区室，更优选的细胞内区室是吞噬体、吞噬溶酶体的溶酶体；更加优选的细胞内区室是吞噬溶酶体。
在本发明的实施方式中，在需要治疗的受试者内，所述感染的宿主细胞优选是真核宿主细胞；所述真核宿主细胞优选选自由以下各项组成的组：专业和非专业吞噬细胞，淋巴细胞，扁桃体组织细胞，呼吸道上皮细胞，颊上皮细胞，骨髓细胞，成骨细胞，角质形成细胞，肌肉细胞，单核细胞，巨噬细胞，树突细胞，内皮细胞，上皮细胞，成纤维细胞，星形胶质细胞和小胶质细胞组成的组；更优选的真核宿主细胞是专业或非专业吞噬细胞。所述受试者可以是对持留细菌感染易感或遭受其感染的任何受试者，例如，但不限于人或动物。动物可以是家养动物，或可以是种畜，宠物，牛，家禽等。优选的受试者是人，并可以是新生儿，少年，成年或老年受试者。
在本发明的实施方式中，提高所述细胞内pH和/或所述细胞内区室的pH的试剂可以是本领域技术人员已知有效提高细胞内pH和/或所述胞内区室的pH的任何试剂。
优选在本发明的实施方式中，提高所述细胞内pH和/或所述胞内区室的pH的试剂是碱化剂，优选亲溶酶体碱化剂(lysosomotropic alkalizing agent)，优选选自由氯喹，巴弗洛霉素A1(bafilomycin A1)，氯化铵组成的组；更优选的碱化剂是氯喹。优选的碱化剂是能够进入所述宿主细胞并更优选靶向其中存在所述感染细菌的细胞内区室的碱性化剂。所述碱化剂可以被动地进入所述细胞或可以使用载体。所述载体可以是本领域技术人员已知的能够递送到宿主细胞中的任何载体。
在本发明实施方式中的所述术语“低pH”定义为低于pH 7.4的pH；优选低pH为约pH7.0、6.8、6.6、6.4、6.2、6.0、5.8、5.6、5.4、5.2、5.0、4.8、4.6、4.4、4.2、4.0、3.8、3.6、4.4、3.2、3.0或约2.8。低pH优选是低于约6.5的pH。更优选的低pH为约5.0。
在本发明的实施方式中，提高pH和升高pH的所述术语可以互换使用，并定义为将所述pH升高约0.2、0.4、0.6、0.8、1.0、1.2、1.4、1.6、1.8、2.0、2.2、2.4、2.6、2.8、3.0、3.2、3.4、3.6、3.8、4.0、4.2、4.4、4.6或约4.8。优选将所述pH提高到约pH 6至约7的范围内；优选提高至约6.5至约7的范围内。
本发明实施方式中的所述术语“有效量”在提高所述细胞内pH值和/或所述细胞内区室pH值的试剂的上下文中定义为足以提高所述细胞内pH和/或细胞内区室的pH至少约0.2、0.4、0.6、0.8、1.0、1.2、1.4、1.6、1.8、2.0、2.2、2.4、2.6、2.8、3.0以达到如上所述的范围的任何用量。所使用的精确用量将尤其取决于所使用的试剂和所述受试者的体重。
在本发明的实施方式中的所述术语“有效量”在杀菌剂的上下文中定义为足以在细胞内和/或所述细胞内区室内具有杀菌作用的任何用量。所使用的精确用量将尤其取决于所使用的试剂和所述受试者的体重。
细胞内pH和细胞内区室的pH能够通过本领域技术人员已知的任何方法进行评价。在本发明的实施方式中，所述杀菌剂可以是本领域技术人员已知的任何杀菌剂，并优选是能够进入所述宿主细胞和/或所述宿主细胞的细胞内区室的杀菌剂。优选的杀菌剂是嵌合杀菌剂。优选的杀菌剂选自由以下各项组成的组：细菌素(bacteriocin)或其功能部分，细菌溶素或自溶蛋白或其功能部分，噬菌体溶素或其功能部分，病毒溶素或其部分，抗微生物肽和抗生素组成的组。进一步优选的杀菌剂是噬菌体衍生的溶解结构蛋白(如尾溶素和病毒体相关的溶解蛋白)或从这种溶解结构蛋白或噬菌体溶素分离的溶解结构域。本发明的杀菌剂可以单独使用或可以以本发明的两种或三种或更多种杀菌剂的组合使用。优选的杀菌剂是能够进入所述宿主细胞的杀菌剂，更优选靶向存在所述感染细菌的细胞内区室。所述杀菌剂可以被动进入所述细胞，或可以使用载体。所述载体可以是本领域技术人员已知的能够递送进入宿主细胞中的任何载体。
所述抗生素可以是本领域技术人员已知的任何抗生素。优选的抗生素选自由以下各项组成的组：β-内酰胺类抗生素如青霉素衍生物、头孢菌素类、单环内酰胺类(monobactams)、碳青霉烯类、万古霉素、达托霉素、氟喹诺酮类、甲硝唑、硝基呋喃妥因(nitrofurantoin)、复方磺胺甲噁唑(co-trimoxazole)、泰利霉素(telithromycin)、氨基糖苷类抗生素；更优选的抗生素是氟氯西林(flucloxacillin)。
所述细菌素可以是本领域技术人员已知的任何细菌素，优选任何I-IV类的细菌素。
本文中的I类细菌素是小肽抑制剂，包括乳酸链球菌肽(nisin)和其他羊毛硫抗生素(lantibiotics)。
本文中的II类细菌素是小(<10kDa)热稳定蛋白。这个类被细分为五个子类。IIa类细菌素(类片球菌素(pediocin)细菌素)是最大的亚组，并且在整个组中含有N-端共有序列-Tyr-Gly-Asn-Gly-Val-Xaa-Cys。所述C-端负责物种特异性活性，通过使所述靶细胞壁透化而引起细胞渗漏。IIb类细菌素(双肽细菌素)需要两种不同的肽用于活性。一种这样的实例是乳球菌素G，其使细胞膜透过单价离子如Na和K，但不透过二价离子。几乎所有这些细菌素都具有GxxxG基序。这种基序也在跨膜蛋白中发现，其中它们参与了螺旋-螺旋相互作用。所述细菌素的GxxxG基序能够与所述细菌细胞的膜中的基序相互作用，并通过如此作用而杀死所述细菌。IIc类包括具有共价连接的N-端和C-端区的环肽。促肠活动素(Enterocin)AS-48就是该组的原型。IId类涵盖不经翻译后修饰和不显示所述类片球菌素特征的单肽细菌素。该组的最佳实例是高度稳定的金丝桃素(aureocin)A53。这种细菌素在高度酸性环境(HCl 6N)下是稳定的，不受蛋白酶和耐热性的影响。最近提出的亚类是IIe类，其涵盖由三个或四个非类片球菌样肽组成的那些细菌素。最好的实例是金丝桃素A70，四肽细菌素，对单核细胞增生李斯特菌具有高度活性，具有潜在的生物技术应用。
III类细菌素是大的热不稳定(>10kDa)蛋白细菌素。这个类别被细分为两个子类：子类IIIa或溶菌素和子类IIIb。IIIa子类涵盖通过细胞壁破坏杀死细菌细胞的那些肽，从而引起细胞裂解。最充分研究的溶菌素是溶葡萄球菌素，一种能够水解几种葡萄球菌细胞壁(主要是金黄色葡萄球菌)的27kDa肽。相比之下，IIIb子类包括不引起细胞溶解的那些肽，通过破坏膜电位而杀死靶细胞，这会导致ATP流出。
IV类细菌素定义为含有脂质或碳水化合物部分的复杂细菌素。确证的实验数据最近才通过两个独立组通过Sublancin和Glycocin F(GccF)的表征得以确立。
优选的细菌素选自由以下各项组成的组：嗜酸乳杆菌素(acidocin)，阿肽加定(actagardine)，土壤杆菌素(agrocin)、阿维西肽(alveicin)、金丝桃素(aureocin)、金丝桃素A53、金丝桃素A70、卡诺霉素(carnocin)、卡诺环素环蛋白(carnocyclin circularin)A、大肠杆菌素(colicin)、曲霉素(Curvaticin)、分歧素(divercin)、耐久霉素(duramycin)、促肠活动素(Enterocin)、肠溶素(enterolysin)、表皮素(epidermin)/gallidermin、erwiniocin、加西葫芦素(gassericin)A、甘氨胆酸(glycinecin)、嗜盐菌素(halocin)、嗜盐耐久素(haloduracin)、乳酸杆菌素(lactocin)S、乳酸乳球菌素(lactococin)、乳酸链球菌素(lacticin)、林可霉素(leucoccin)、溶葡萄球菌马赛多蛋白(lysostaphin macedocin)、美杀菌素(mersacidin)、肠系膜菌素(mesentericin)、小双孢菌素(microbisporicin)、小菌素(microcin)S、变链素(mutacin)、乳酸乳链菌肽(nisin)、类芽孢杆菌素(paenibacillin)、平滑孢菌素(planosporicin)、片球菌素(pediocin)、戊糖乳杆菌素(pentocin)、植物乳杆菌素(plantaricin)、脓菌素(pyocin)、reutericin 6、米酒乳杆菌素(sakacin)、唾窦菌素(salivaricin)、枯草杆菌素(subtilin)、硫叶菌素(sulfolobicin)、苏云金菌素(thuricin)17、三叶草素(trifolitoxin)、变异菌素(variacin)、弧菌素(vibriocin)、warnericin和warnerin。
所述细菌素可以来自细菌本身(24)，例如但不限于，来自绿脓假单胞菌的脓菌素，优选脓菌素SA189(25)。
所述抗微生物肽可以是本领域技术人员已知的任何抗微生物肽。有时在本领域中，所述抗微生物肽被认为是上文列出的细菌素。优选的抗微生物肽选自由阳离子或多阳离子肽、两亲肽、寿司肽(sushi peptide)、防御素和疏水肽组成的组。
所述细菌自溶蛋白可以是本领域技术人员已知的细菌自溶素。优选的细菌自溶蛋白是LytM。
所述噬菌体溶素可以是本领域技术人员已知的任何噬菌体溶素。本文中，所述术语噬菌体溶素，噬菌体内溶素和内溶素可以互换使用。优选的内溶素选自由WO2012/150858、WO2013/169104、WO2011/023702和WO2012146738中定义的组，以其全部内容结合于本文中作为参考。
所述杀菌剂可以是上述的任何试剂或其功能片段。本文中所述术语功能片段与所述术语功能结构域能够互换使用。功能性片段在本文中定义为与所述功能片段衍生的所述母体相比在相同条件下测定时具有至少20％、30％、40％、50％、60％、70％、80％、95％、95％或99％或至少或99.9％的杀菌活性的片段。杀菌剂的优选功能片段描述于WO2012/150858和WO2013/169104中。
所述杀菌剂可以是杀菌剂和杀菌剂功能性片段的融合物，或可以是不同的，相似的或相同的杀菌剂或杀菌剂功能片段的融合物。
本发明人已经得到所述令人惊奇的发现，当所述杀菌剂靶向进入所述宿主细胞时，根据本发明的治疗方法的效率大大提高。这种靶向可以通过本领域技术人员已知的任何方式实现，这在上文已经描述。优选的方法是可操作地连接到所述杀菌剂的蛋白质转导结构域；本文进一步称为根据本发明的蛋白转导结构域。所述术语“蛋白转导结构域”在本文中与所述术语“细胞可渗透蛋白(CPP)”和所述术语“膜易位序列”能够互换使用。可操作地连接在本文中定义为蛋白转导结构域与靶向进入所述细胞的杀菌剂的结合。优选的可操作连接是通过蛋白转导结构域与所述杀菌剂的共价结合的融合。
在本发明的实施方式中，所述杀菌剂优选包含细胞壁溶解酶的功能性酶促结构域。细胞壁溶解酶在本文中定义为作用于其有效抵抗的所述细菌的细胞壁的任何杀菌剂。
优选在本发明的实施方式中所述杀菌剂包含来自细胞壁溶解酶的功能结构域，并进一步包含根据本发明的蛋白转导结构域。优选在根据本发明的实施方式中所述杀菌剂可以进一步包含抗微生物肽。这种融合杀菌剂优选是与选自由阳离子或多阳离子肽，两性肽，寿司肽，防御素和疏水性肽组成的组中的抗微生物肽融合的细胞壁溶解酶，更优选是US8,383,102中所定义的融合蛋白，该专利以其全部内容结合于本文中作为参考。与抗微生物肽融合的这种杀菌剂可以进一步包含根据本发明的蛋白转导结构域。
在本发明的实施方式中，包含细胞壁裂解酶的功能性酶促结构域和/或包含蛋白质转导结构域和/或包含抗微生物肽的如上所述杀菌剂可以另外优选进一步包含细胞壁结合结构域。所述细胞壁结合结构域优选是结合所述细菌的肽聚糖(peptidoglycan)细胞壁导致所述细菌感染受到治疗的细胞壁结合结构域。
在本发明的实施方式中，所述蛋白质转导结构域可以是本领域技术人员已知的任何这种结构域。优选在根据本发明的杀菌剂中所述蛋白质转导结构域选自由SEQ ID NO:12-25，或其变体组成的组，其中所述变体是功能性蛋白转导结构域，并分别与选自由SEQID NO:12-25组成组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％序列一致性。
优选在根据本发明的杀菌剂中，来自细胞壁溶解酶的功能性酶促结构域选自由SEQ ID NO:1-7，或其变体组成的组，其中所述变体来自细胞壁溶解酶的功能性酶促结构域，并分别与选自由SEQ ID NO:1-7组成组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性。
优选在根据本发明的杀菌剂中，所述细胞壁结合结构域选自由SEQ ID NO:8-11，或其变体组成的组，其中所述变体是功能性细胞壁结合结构域，并分别与选自由SEQ IDNO:8-11组成组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性。
优选在根据本发明的杀菌剂中，所述抗微生物肽选自由SEQ ID NO:70-90，或其变体组成的组中，其中所述变体是功能性细胞壁结合结构域，并分别与选自由SEQ ID NO:70-90组成组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性。
根据本发明的优选杀菌剂是与选自由SEQ ID NO:27，28，29，30-47组成组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性的杀菌剂，或是由与选自由SEQ ID NO:50-67组成组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％序列一致性的多核苷酸序列编码的杀菌剂。
根据本发明的优选的杀菌剂是来自具有与选自由SEQ ID NO:91-108组成组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性的序列的载体的表达产物。
根据本发明的进一步优选的杀菌剂是选自由以下各项组成的组中的杀菌剂：包含选自由SEQ ID NO:12-25，或其变体组成的组中的蛋白转导结构域，选自由SEQ ID NO:1-7或其变体组成的组中的来自细胞壁溶解酶的功能性酶促结构域，和可选的选自由SEQ IDNO:8-11或其变体组成的组中的细胞壁结合结构域和/或选自由SEQ ID NO:70-90或其变体组成的组的抗微生物肽的杀菌剂；其中变体与各自的原始序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％或100％的序列一致性。
就治疗方法而言，这个方面涉及生产用于治疗需要其的受试者的细菌感染的药物的这方面的实施方式。就治疗方法而言，该方面涉及用于治疗需要其的受试者的细菌感染的这方面的实施方式。
在第二方面中，本发明提供了包含来自选自由SEQ ID NO:1-7，或其变体组成的组中的细胞壁溶解酶的功能酶结构域，其中所述变体是来自细胞壁溶解酶的功能性酶促结构域并分别与选自由SEQ ID NO:1-7组成的组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性；和选自由SEQ ID NO:12-25，或其变体组成的组中的蛋白转导结构域，其中所述变体是功能性蛋白转导结构域，并分别与选自由SEQ ID NO:12-25的组成的组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，或99％或100％的序列一致性；和可选地包含选自由SEQ ID NO:8-11，或其变体组成的组中的细胞壁结合结构域，其中所述变体是功能性细胞壁结合结构域并分别与选自由SEQ ID NO:8-11组成的组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性；和/或选自由SEQ ID NO:70-90，或其变体组成的组中的抗微生物肽，其中所述变体是功能性细胞壁结合结构域并分别与选自由SEQ IDNO:70-90组成的组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性的嵌合杀菌多肽。
本发明还提供了与选自由SEQ ID NO:27，28，29，30-47组成的组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％或99％或100％的序列一致性的嵌合杀菌多肽，或由与选自由SEQ ID NO:50-67组成的组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性的多核苷酸序列编码的嵌合杀菌剂。
本发明还提供了一种嵌合杀菌多肽选自由以下各项组成的组：包含选自由SEQ IDNO:12-25，或其变体组成的组中的蛋白转导结构域，选自由SEQ ID NO:1-7，或其变体组成的组中的来自细胞壁溶解酶的功能性酶促结构域，和可选的选自由SEQ ID NO:8-11，或其变体组成的组中的细胞壁结合结构域，和/或选自由SEQ ID NO:70-90或其变体组成的组的抗微生物肽的杀菌剂；其中所述变体与各自原始序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性。
本发明进一步提供编码根据本发明该方面的嵌合杀菌多肽的多核苷酸。
本发明进一步提供了包含编码本发明的嵌合杀菌多肽的多核苷酸的多核苷酸构建体。
本发明进一步提供了用于表达和生产根据本发明的嵌合杀菌多肽的载体。根据本发明的载体优选包含根据本发明的多核苷酸构建体，其含有编码根据本发明的嵌合杀菌多肽的多核苷酸。根据本发明的优选载体是具有与选自由SEQ ID NO:91-108组成的组中的序列具有至少40％，45％，50％，60％，65％，70％，75％，80％，85％，90％，95％，96％，97％，98％，99％或100％的序列一致性的序列的载体。
本发明进一步提供了用于生产根据本发明的嵌合杀菌多肽的宿主细胞，其包含根据本发明的多核苷酸构建体或载体。所述宿主细胞可以是适合于生产根据本发明的嵌合杀菌多肽的任何宿主细胞，如原核和真核宿主细胞。
本发明进一步提供了根据本发明的嵌合杀菌多肽的生产，其包括在有利于生产本发明的嵌合杀菌多肽的条件下培养根据本发明的宿主细胞，其包含根据本发明的多核苷酸构建体或载体，和可选地分离和/或纯化所生产的嵌合杀菌多肽。
任何合适的给药途径都能够用于给予根据本发明的碱化剂和根据本发明的杀菌剂，包括但不限于，口服，气溶胶或用于递送至肺的其它器件，鼻喷雾，静脉内，肌肉内，腹膜内，鞘内，阴道，直肠，局部，腰椎穿刺，鞘内注射，直接施用于脑和/或脑膜。根据本发明的碱化剂和根据本发明的杀菌剂可以至少每天一次，每周一次，每月一次，每六个月一次，每年一次或无论怎样适合所述治疗的方案向需要其的受试者或所述受试者的细胞、组织或器官给药。
在本文件及其权利要求中，所述动词“包含”及其结合体(conjugation)在其非限制意义上是指所述词后面的项目(item)包含在内，但不排除未明确提及的项目。另外，通过不定冠词“一种”或“一个”提及要素不排除存在多于一个所述要素的可能性，除非上下文清楚地要求存在一个且唯一的要素。因此，不定冠词“一种”或“一个”通常是指“至少一个”。
当与数值(例如，约10)关联使用时，所述词“约”或“大约”优选是指该值可以是给定值(10)多出或少了所述值的0.1％的值。
本说明书中引用的所有专利和参考文献都以其全部内容结合于本文中作为参考。
本文中，与具体序列的序列一致性优选是指在所述具体多肽或多核苷酸序列的整个长度内的序列一致性。本文提供的所述序列信息不应如此狭义地解释为需要包含错误识别的碱基。本领域技术人员能够识别这种错误识别的碱基，并知道如何校正这种错误。
通过将一个肽或多肽的氨基酸序列及其保守的氨基酸取代物与第二个肽或多肽的序列比较就能确定两个氨基酸序列之间的“相似性”。优选在本文中确定的整个SEQ IDNO内计算一致性或相似性。“一致性”和“相似性”能够通过已知方法很容易计算，包括但不限于，Computational Molecular Biology，Lesk，A.M.，ed.，Oxford University Press，New York，1988；Biocomputing：Informatics and Genome Projects，Smith，D.W.，ed.，Academic Press，New York，1993；Sequence Analysis of Sequence Data，Part I，Griffin，A.M.and Griffin，H.G.eds.，Humana Press，New Jersey，1994；SequenceAnalysis in Molecular Biology，von Heine，G.，Academic Press，1987；and SequenceAnalysis Primer，Gribskov，M.and Devereux，J.，eds.，M Stockton Press，New York，1991；and Carillo，H.and Lipman，D.，SIAM J.Amerge Math.，48：1073(1988)中公开的那些。
确定一致性的优选方法经过设计而在测试的序列之间给出最大的匹配。确定一致性和相似性的方法在公共可用的计算机程序中编成。确定两个序列之间的一致性和相似性的优选计算机程序方法包括，例如，GCG程序包(Devereux，J.，et al.，Nucleic AcidsResearch 12(1)：387(1984))，BestFit，BLASTP，BLASTN和FASTA(Altschul，SF et al.，J.Mol.Biol.215：403-410(1990))。所述BLAST X程序能够从NCBI和其他来源(BLASTManual，Altschul，S.，et al.，NCBI NLM NIH Bethesda，MD20894；Altschul，S.，et al.，J.Mol.Biol.215：403-410(1990))公开地获取。众所周知的Smith Waterman算法也可以用于确定一致性。
多肽序列比对的优选参数包括以下这些：算法：Needleman和Wunsch，J.Mol.Biol.48：443-453(1970)；Comparison matrix:BLOSSUM62，获自Hentikoff andHentikoff,Proc.Natl.Acad.Sci.USA.89:10915-10919(1992)；Gap Penalty:12；和GapLength Penalty:4。与这些参数一起可用的程序是可以公开地获得的来自位于美国威斯康星麦迪逊的遗传计算机集团(Genetics Computer Group)的“Ogap”程序。上述参数是氨基酸比对的默认参数(连同端隙无罚分一起)。
用于核酸比对的优选参数包括以下这些：算法：Needleman and Wunsch，J.Mol.Biol，48：443-453(1970)；Comparison matrix:matches＝+10，mismatch＝0；GapPenalty:50；Gap Length Penalty:3。作为所述Gap程序(来自位于美国威斯康星麦迪逊的遗传计算机集团)可获得。以上提供的都是核酸比对的默认参数。
可选的是，在确定氨基酸相似性程度时，所述技术人员也可以考虑所谓的“保守”氨基酸取代，这对本领域技术人员将是清楚的。保守氨基酸取代是指具有相似侧链的残基的可互换性。例如，具有脂族侧链的一组氨基酸是甘氨酸，丙氨酸，缬氨酸，亮氨酸和异亮氨酸；一组具有脂族-羟基侧链的氨基酸是丝氨酸和苏氨酸；一组具有含酰胺侧链的氨基酸是天冬酰胺和谷氨酰胺；具有芳族侧链的一组氨基酸是苯丙氨酸，酪氨酸和色氨酸；具有碱性侧链的一组氨基酸是赖氨酸，精氨酸和组氨酸；一组具有含硫侧链的氨基酸是半胱氨酸和甲硫氨酸。优选的保守氨基酸取代基是：缬氨酸-亮氨酸-异亮氨酸，苯丙氨酸-酪氨酸，赖氨酸-精氨酸，丙氨酸-缬氨酸和天冬酰胺-谷氨酰胺。本文公开的氨基酸序列的取代变体是其中所公开序列中的至少一个残基已经被去除以及不同残基插入其位置的那些。优选所述氨基酸变化是保守的。每个天然存在的氨基酸的优选保守取代如下：Ala取代成ser；Arg取代成lys；Asn取代成gln或his；Asp取代成glu；Cys取代成ser或ala；Gln取代成asn；Glu取代成asp；Gly取代成pro；His取代成asn或gln；Ile取代成leu或val；Leu取代成ile或val；Lys取代成arg；gln或glu；Met取代成leu或ile；Phe取代成met,leu或tyr；Ser取代成thr；Thr取代成ser；Trp取代成tyr；Tyr取代成trp或phe；和Val取代成ile或leu。
多核苷酸由核苷酸序列表示。多肽由氨基酸序列表示。
表1.序列
Figure GDA0001462223680000121
Figure GDA0001462223680000131
Figure GDA0001462223680000141
Figure GDA0001462223680000151
Figure GDA0001462223680000161
Figure GDA0001462223680000171
Figure GDA0001462223680000181
附图说明
图1a至图1f
通过低pH和凭借pH升高的细菌再生长诱导金黄色葡萄球菌SCV和非复制性持留菌。
将MRSA金黄色葡萄球菌菌株6850(图1a)，JE2(图1b)和Cowan(图1c)接种于如所示的不同pH下缓冲的培养基中。确定存活细菌的菌落表型，并随时间对SCV百分数绘图。一式三份完成的三次独立实验表示成平均值±SEM。
将低pH诱导的MRSA金黄色葡萄球菌菌株6850(图1d)，JE2(图1e)和Cowan(图1f)持留菌在所示的各种缓冲pH介质中重新接种，并随着时间推移生长。以一式三份完成的三次独立实验表示为平均值±SEM。
图2a至图2b
金黄色葡萄球菌在吞噬溶酶体内的细胞内持留。
A549细胞用金黄色葡萄球菌Cowan感染，细胞外细菌通过加入氟氯西林杀死。在指定的时间点测定活的细胞内持留细菌的数目(图2a)和表型(图2b)。由一式三份实施的两次实验汇集数据，平均值±SEM。
图3a至图3c
金黄色葡萄球菌持留菌通过吞噬溶酶体碱化而减少。金黄色葡萄球菌Cowan感染的A549细胞用单独氟氯西林(对照)或补充有亲溶酶体碱化剂(氯喹(图3a)，巴弗洛霉素A1(图3b)和氯化铵(图3c))处理。在指定的时间点测定并计数活的细胞内持留细菌的菌落表型。由以一式三份完成的三次独立实验收集数据，平均值±SEM。双因素ANOVA发现所述因素时间和处理是显著的(p值<0.01)。
图4a至图4c
在体内感染模型中通过氯喹降低金黄色葡萄球菌持留菌。
小鼠腹膜内感染金黄色葡萄球菌Cowan。感染后6小时和2天，小鼠用1mg氟氯西林和0.2mg氯喹(+CQ)处理。仅用氟氯西林处理的小鼠作为对照(-CQ)。
Figure GDA0001462223680000191
处死(图4a)。确定并计数从靶组织(图4b)，外周血和腹膜灌洗液(图4c)中回收的细菌菌落表型。每个点代表一只小鼠。水平条棒表示平均值±SEM，n＝11只小鼠/组。PL，腹腔灌洗。双因素ANOVA发现所述因素处理是显著的(p值<0.01)。
图5a至图5d
通过工程化内溶素的混合物将金黄色葡萄球菌胞内靶向于骨肉瘤细胞中。(图5a)金黄色葡萄球菌Newman(MOI 0.1)感染3小时的细胞用内溶素混合物处理1小时和4小时。(图5b)在20μM氯喹存在下，金黄色葡萄球菌Newman(MOI 0.1)感染3小时的细胞通过内溶素混合物处理1小时和4小时。(图5c)用金黄色葡萄球菌Cowan(MOI 0.01)感染3小时的细胞通过内溶素混合物处理1小时和4小时。(图5d)在20μM氯喹存在下，金黄色葡萄球菌Cowan(MOI0.01)感染3小时的细胞通过内溶素混合物处理1小时和4小时。
图6a至图6d
通过工程化的内溶素的混合物将金黄色葡萄球菌胞内靶向于骨肉瘤细胞(MOI1.0)中。(图6a)用金黄色葡萄球菌Newman感染24小时的细胞通过内溶素混合物处理4小时。(图6b)用金黄色葡萄球菌Newman感染24小时的细胞在20μM氯喹存在下通过内溶素混合物处理4h。(图6c)用金黄色葡萄球菌Cowan感染细胞72小时的细胞通过内溶素混合物处理4小时。(图6d)在20μM氯喹存在下，用金黄色葡萄球菌Cowan感染72小时的细胞通过内溶素混合物处理4小时。
图7a至图7e
包含来自细胞壁溶解酶的功能性酶促结构域并在所述分子的N-端侧进一步包含蛋白转导结构域的本发明的杀菌剂的活性：(图7a)R9-CHAP-CBD，(图7b)R9-M23-CBD，(图7cTAT-Ami-CBD，(图7d)TAT-CHAP-CBD和(图7e)TAT-M23-CBD。
具体实施方式
实施例
通过以下实施例进一步描述本发明，这些实施例不应解释为限制本发明的范围。
除非另有说明，本发明的实践将采用分子生物学，病毒学，微生物学或生物化学的标准常规方法。这些技术描述于文献Sambrook et al.(1989)Molecular Cloning,ALaboratory Manual(2nd edition),Cold Spring Harbor Laboratory,Cold SpringHarbor Laboratory Press；in Sambrook and Russell(2001)Molecular Cloning:ALaboratory Manual,Third Edition,Cold Spring Harbor Laboratory Press,NY；inVolumes 1 and 2 of Ausubel et al.(1994)Current Protocols in MolecularBiology,Current Protocols,USA；and in Volumes I and II of Brown(1998)MolecularBiology LabFax,Second Edition,Academic Press(UK)；Oligonucleotide Synthesis(N.Gait editor)；Nucleic Acid Hybridization(Hames and Higgins,eds.)中。
实施例1
金黄色葡萄球菌持留菌通过低pH诱导，通过吞噬溶酶体碱化反应唤醒和通过吞噬 体碱性化与杀菌剂的组合有效治疗。
1.1金黄色葡萄球菌小菌落变异体(SCV)的pH依赖性诱导
明确定义的MSSA菌株6850和Cowan和MRSA菌株JE2生长于pH4.0、5.5、6.5和7.4培养基中，模拟生理位点如溶酶体，脓肿和血液中发现的pH。直接地在接种后，金黄色葡萄球菌显示出大的菌落表型，与所述pH无关。在pH 4.0生长培养基中，SCV的频率随时间显著增加，五天后达到39％(JE2和6850)和28％(Cowan)。相比而言，在所有测试的菌株中，pH 7.4生长培养基保持SCV低于2％(图1a-图1c)。在pH 5.5和6.5下发现了中等百分比的SCV。因此，我们揭示了低pH和SCV形成之间的明确相关性。这种方法允许在各种金黄色葡萄球菌菌株中容易且受控形成不稳定的非基因修饰的SCV。
1.2通过低pH诱导非复制型金黄色葡萄球菌
随着时间的推移，金黄色葡萄球菌Cowan的所述pH依赖性生长后用荧光细胞壁结合结构域(CBD)标记所述细菌细胞壁。染色后立即将细菌细胞壁完全标记。在pH 4.0生长培养基中三天后，大多数细菌仍然呈现荧光细胞壁，与无细菌复制一致。相比之下，在pH 7.4生长的细菌通过高度片段化和89降低的荧光细胞壁标记证实发生了广泛的增殖。在低pH条件下获得的来自小菌落的细菌的扫描电子显微镜(SEM)显示出细胞分裂受损，导致产生棒状金黄色葡萄球菌，与显示正常细胞分裂的大菌落细菌相对。
1.3低pH适应金黄色葡萄球菌持留菌的生长恢复
我们的发现表明，SCV和非复制性持留菌都是由低pH诱导的。在临床中，这些持留细菌的存在与增加的感染复发有关，这意味着细菌会返回到高毒力和快速生长的形式14。因此，我们在体外测试了低pH诱导的SCV和/或非复制性持留菌是否能够恢复中性pH值中的正常生长。诱导了非复制型金黄色葡萄球菌持留菌并保持于pH 4.0下3天，然后转移至pH4.0、5.5、6.5或7.4生长培养基中。pH 7.4和6.5的细菌在大约12小时后恢复生长(图1d-图1f)，而保持于低pH值(<6.5)的细菌保持非增殖状态(图1d-图1f)。这些数据表明，持留表型对低pH具有可逆适应性，这由pH中和后的再生长能力支持。
1.4金黄色葡萄球菌SCV的细胞内诱导
我们研究了内化金黄色葡萄球菌是否会表现出SCV表型。MSSA菌株Cowan是高侵袭性的，但不是细胞毒性的，其允许该菌株在肺上皮细胞系A549中细胞内保持数天。通过向所述感染的宿主细胞中加入高剂量的氟氯西林而杀死细胞外细菌。氟氯西林通常用于治疗患者的金黄色葡萄球菌心内膜炎(endocarditis)。通过培养物上清液的无菌性证实不存在细胞外细菌。宿主细胞溶解而释放细胞内细菌并在不同的时间点测定菌落数以及菌落表型。感染后5小时，0.2％的所有活的细胞内细菌具有SCV表型(图2a-图2b)。感染过程中活的细胞内持留细菌的数量减少，而SCV的频率增加并在七天后达到5.6％。
1.5持留金黄色葡萄球菌的吞噬溶酶体定位
我们的数据表明，酸度有利于SCV形成，这表明所述酸性吞噬溶酶体系环境可能具有相同的效果。A549细胞用金黄色葡萄球菌Cowan感染。细胞内细菌定位于LAMP-2抗体阳性囊泡内，通过荧光显微镜观察。LAMP-2(CD 107b)在吞噬溶酶体中高度表达，这表明细胞内持留金黄色葡萄球菌主要存在于吞噬溶酶体内。
1.6通过吞噬溶酶体碱化降低金黄色葡萄球菌SCV
由于低pH诱导的SCV和/或非复制性金黄色葡萄球菌和中等pH中和会导致细菌再生长，我们用亲溶酶体碱化剂处理受感染的宿主细胞。氯喹，巴弗洛霉素A1或氯化铵全都会中和所述吞噬溶酶体pH。在感染后7天用亲溶酶体碱化剂处理的宿主细胞表现出显著较低的SCV百分比(图3a至图3c)。没有观察到对照和所处理的细胞之间的总菌落计数的差异。亲溶酶体碱化剂在所用的浓度下并未抑制细菌生长。在用碱化剂处理后，观察到宿主细胞活力没有显著差异。
1.7通过氯喹处理的吞噬溶酶体内持留金黄色葡萄球菌的生长恢复导致细胞和小 鼠中SCV百分比降低
评价了通过用氯喹处理宿主细胞的金黄色葡萄球菌持留菌的生长恢复。荧光显微镜揭示出感染后3天金黄色葡萄球菌位于对照宿主细胞和氯喹处理宿主细胞两者中的吞噬溶酶体内。我们在未用氯喹处理的受感染宿主细胞中没有观察到细菌分裂。然而，通过透射电子显微镜(TEM)评价，氯喹会促进细菌细胞分裂。
感染金黄色葡萄球菌Cowan的小鼠单独用氟氯西林(对照物)或用氟氯西林与氯喹组合治疗(图5a)。氯喹治疗显著降低了各种器官(图5b)和区室(图5c)内小鼠的SCV的频率。绝对细菌数量是可比较的，与氯喹处理无关。
1.8讨论
这项研究表明，正如在脓肿和溶酶体内发现的，低pH会诱导持留金黄色葡萄球菌亚群SCV和非复制性持留菌。使用碱化剂升高所述培养基或所述吞噬溶酶体内pH会使金黄色葡萄球菌返回至正常生长。SCV形成被证明是由抗生素压力引起的。此外，极端的环境应力，如长时间暴露于低温，非常酸性或碱性的环境，或渗透胁迫(stress)，可能会导致金黄色葡萄球菌和凝固酶阴性葡萄球菌中的SCV和/或持留菌形成。这些观察结果与我们的新发现一起证实了多种刺激如何导致金黄色葡萄球菌持留菌形成。所述宿主细胞内的定位会保护金黄色葡萄球菌免于通常使用的抗生素如细胞外具有活性而细胞穿透性较差的β-内酰胺损伤。另外，低的吞噬溶酶体内pH会使具有细胞内活性的抗生素如克林霉素(clindamycin)和氟喹诺酮(fluoroquinolone)活性变差。我们发现亲溶酶体碱化剂添加到通常处方用抗生素如氟氯西林中会降低金黄色葡萄球菌SCV在体外和体内的频率。因此，我们确定了一个简单的策略以规避金黄色葡萄球菌持留菌形成的宿主依赖分量。在临床环境中，尽管给予抗生素，SCV在骨髓炎和器件相关感染中的存在与复发率增加有关。细菌通过SCV和/或持留菌形成适应抗生素胁迫(stress)。我们现在证实，金黄色葡萄球菌SCV和非复制性持留菌保留了返回到高度毒性和快速生长形式的能力。返回到快速生长(表型转换)的能力导致感染复发。此外，它使SCV的识别变得困难。在临床上进一步加重SCV问题是临床微生物实验室中SCV的低估，因为它们形成微小，因此难以检测出由其快速增长的对应物(counterpart)容易过度生长的菌落。我们假设，将碱化剂添加到通常处方用抗生素中将会降低SCV的频率，因此可能会在将来降低复发率。持留细菌并不是金黄色葡萄球菌所独有的，但也被描述为发生于其他各种人类病原体，如沙门氏菌属，铜绿假单胞菌，大肠杆菌和结核分枝杆菌中。除了低pH之外，由于包括毒素-抗毒素系统的机制，可能会出现细菌持留菌。因此，由于氧化胁迫响应DNA破坏的SOS响应的活化(ppGpp)会导致ATP水平降低。这会导致代谢的停止，引起生长降低。各种毒素-抗毒素模块通过沙门氏菌的酸化和/或营养饥饿而活化，引起持留菌形成。根据我们的发现，沙门氏菌持留菌形成已经报道于由通过加入巴弗洛霉素A1 44是可逆的含沙门氏菌液泡的酸性和营养不良环境触发的巨噬细胞中。与巴弗洛霉素A1相反，氯喹常规用于患者以治疗疟疾以及一些风湿性疾病。因此，利用氯喹的吞噬溶酶体pH中和可以提供针对细胞内持留的葡萄球菌保留物(reservoir)的新型治疗性根除策略。
实施例2
通过吞噬溶酶体碱化与含有蛋白转导结构域的杀菌剂组合有效地治疗金黄色葡 萄球菌持留菌。
具有用于有效递送到所感染的宿主细胞中的具有选自由SEQ ID NO:30-47组成的组中的序列的蛋白转导结构域的根据本发明的杀菌剂用于与吞噬溶酶体pH中和组合从而体外和体内治疗细胞内金黄色葡萄球菌感染。这种处理导致了所述细胞内金黄色葡萄球菌感染的有效治疗，所述效率上的某些变化取决于所使用的根据本发明的特异性杀菌剂。
实施例3
金黄色葡萄球菌细胞内感染的有效治疗
具有用于有效递送到所感染的宿主细胞中，具有选自由SEQ ID NO:27-47组成的组中的序列的蛋白转导结构域的根据本发明的杀菌剂用于与吞噬溶酶体pH中和组合或不与吞噬溶酶体pH中和组合来治疗细胞内金黄色葡萄球菌感染。
细胞内金黄色葡萄球菌杀伤测试的方法
金黄色葡萄球菌在LB肉汤中37℃下以220rpm摇动生长过夜。将过夜培养物在新鲜LB中稀释(1:10)，并进一步生长2小时。然后将细菌离心，用PBS洗涤所述球粒，并将培养物重新悬浮于PBS中，用OD600调节至0.4(约2×108CFU/mL)。细菌细胞在感染前(SONOPULS HD2070)以40％的功率1秒脉冲超声处理1分钟。MG-63骨肉瘤细胞在含有10％胎牛血清(FBS)的1mL EMEM培养基中以5×105个细胞/孔的用量生长于12-孔板中长达24小时才进行感染。然后，在以下条件下用金黄色葡萄球菌Newman和Cowan感染细胞：(A)MOI＝0.1下金黄色葡萄球菌Newman长达3h，(B)金黄色葡萄球菌Newman在MOI＝1.0下长达24h，和(C)金黄色葡萄球菌Cowan在MOI＝1.0下长达72h。将所述孔板以1200rpm离心5分钟，并在37℃下在CO2吹扫下进行孵育。在侵袭后，将真核细胞用PBS洗涤3次以除去剩余的细胞外金黄色葡萄球菌，并暴露于氟氯西林(1mg/mL)达2小时以杀死任何剩余的未内化的细菌。对于每个实验(A，B和C)，一部分样品暴露于氯喹处理(20μM)以提高溶酶体pH并评价其对内溶素进一步处理的影响。将来自抗生素处理的细胞的上清液铺板从而检查氟氯西林处理效率。然后，用PBS(3×)再次洗涤所述真核细胞从而除去死细菌并进行内溶素处理。所施用的内溶素制剂的组成总结于表2中。真核细胞用1mL 1μM内溶素制剂(稀释于补充有1mg/mL氟氯西林和+/-20μM氯喹的EMEM中)处理长达(A)1h和4h，(B和C)4h。所述对照物用在EMEM中的1mL 1mg/mL氟氯西林，+/-20μM氯喹进行处理。然后将所述培养物用PBS洗涤3次，并在显微镜下检查以确定是否存在成骨细胞溶解。接着，将其胰蛋白酶消化(胰蛋白酶-EDTA 0.25％，
Figure GDA0001462223680000241
)并用800μL0.1％Triton X-100溶解。所述细胞溶解物在LB上进行连续稀释铺板，并在37℃下过夜孵育。
表2用于金黄色葡萄球菌细胞内根除的所述内溶素混合物的组成
Figure GDA0001462223680000242
结果
实现了所有蛋白构建体的成功表达和纯化。具有相应分子量和浓度的所有表达的内溶素构建体的总结显示于表3中。对于大多数内溶素构建体获得了相对高的浓度，这表明使用了正确的蛋白表达和纯化策略。
表3具有相应分子量和浓度的所有表达的内溶素构建体的总结
Figure GDA0001462223680000243
Figure GDA0001462223680000251
所有表达的内溶素在孔板测试和时间-杀伤测试中对于杀灭金黄色葡萄球菌Cowan都是有效的。
细胞内金黄色葡萄球菌杀伤测试
进一步测试表2中列出的内溶素构建体的混合物在细胞组织培养物中的细菌杀伤效力。
在我们的模型中，使用MG-63骨肉瘤细胞模拟骨髓炎的病情。首先细胞用病原体金黄色葡萄球菌Newman或Cowan感染细胞一段时间，然后在存在或不存在氯喹的情况下用内溶素混合物处理。我们预计通过施用氯喹提高细胞内pH会为内溶素活性创造更有利的条件。
骨肉瘤细胞暴露于金黄色葡萄球菌Newman和Cowan长达3h，然后2h氟氯西林处理以灭活任何未内化的细菌。然后，用含有和不含氯喹的1μM内溶素混合物处理所述组织细胞长达1h和4h。所述结果如图5a至图5d所示。图5a显示了仅通过内溶素混合物处理金黄色葡萄球菌Newman的结果，而图5b显示了用氯喹的组合处理的结果。显然，4h处理在两个实验环境中更有效。此外，在氯喹存在下的内溶素处理导致了细菌计数减少较大。有趣的是，无CPP内溶素的混合物显示出非常好的杀灭效果，这是未预料到的。然而，与CBD相关的大量正电荷可能会将所述酶吸引到带负电荷的细胞膜并诱导其细胞内易位(translocation)。这种无CPP内溶素易位的推定机理是CPP易位的关键。尽管它们的活性差异大体上取决于CBD的存在和CPP标记的类型，但所有内溶素混合物在该测试中都显示出类似的杀灭性能。依据CPP、EAD和CBD的存在，不同的构建体可能具有不同的渗透性能。例如，EAD-CBD混合物具有非常高的活性，但经过细胞膜传输可能不会与任何含CPP的变体一样有效。然而，EAD-CPP构建体没有如此高活性，但较小并含有转导结构域，这使得它们的细胞内转运更有效，并且由于酶在由CBD结合介导的细胞表面上缺乏固定，因此其扩散性更好。因此，具有不同性质的酶可能最终给出了类似的结果。
图5c和图5d显示了用所述病原的不同菌株：金黄色葡萄球菌Cowan进行的相同实验的结果。在这种情况下，所述处理似乎没有效果。对于所述两个样品，不用氯喹(图5c)和采用氯喹(图5d)时，所述活细胞计数的减少可以忽略不计。在氯喹存在下，只有使用CHAP-CBD-R9+M23-CBD-R9混合物进行处理才显著消除了病原体。已知的是，金黄色葡萄球菌Cowan在细胞内存在于溶酶体中。金黄色葡萄球菌Newman的细胞内定位很可能是不同的—它可能只是驻留于细胞质中，因此两个实验的结果是不同的。此外，CPP-标记的内溶素构建体的细胞内命运在这一点上是未知的，因此只可能推测与R9标记融合的内溶素构建体是在溶酶体中积累的唯一事物，因此它们对金黄色葡萄球菌Cowan显示出良好的杀灭性能。
为了模拟现实生活感染，骨肉瘤组织细胞在治疗前用金黄色葡萄球菌感染长达24h和72h。如此长的感染时间使所述细菌在细胞内沉降到其最终目的地。再次，所述细胞在存在和不存在氯喹的情况下用内溶素构建体的混合物处理。图6a和图6b分别显示了在不存在和存在氯喹的情况下用金黄色葡萄球菌Newman感染24小时的骨肉瘤细胞的治疗结果。图6c和图6d对应于用金黄色葡萄球菌Cowan感染72小时的所处理细胞的结果。在这两种情况下，用内溶素混合物处理，特别是加入氯喹时，似乎是有效的。在氯喹存在下，用EAD-CBD-R9混合物处理金黄色葡萄球菌Newman获得最佳结果，其中约60％的病原体被根除(图6b)。用EAD-CBD，EAD-CBD-TAT，EAD-CBD-R9和EAD-CBD-穿透肽的混合物处理的金黄色葡萄球菌Cowan获得了同样良好的结果，其中约50％的病原体被杀灭。一般而言，含CBD的内溶素构建体显示出更好的杀灭效力，包括并未与转导结构域融合的EAD-CBD混合物。
总之，这证明了通过工程化的内溶素与氯喹一起治疗细胞内金黄色葡萄球菌比没有氯喹时的效果更好。这种碱化剂的应用可能会在细胞内增强溶解酶的活性，并且内溶素与氯喹的组合处理可能是常规抗生素治疗的良好替代方法。
总之，本研究揭示了CPP-融合的内溶素在细胞内和细胞外金黄色葡萄球菌的治疗中的潜力。这种治疗方法能够用于治疗患有比如，例如，骨髓炎，心内膜炎，菌血症或败血症的疾病的患者，以及奶牛的牛乳腺炎。
实施例4
根据本文中别处描述的方法制备和分析了含有来自细胞壁溶解酶的功能酶结构域并进一步在所述分子的N-端侧上含有蛋白转导结构域的根据本发明的多种杀菌剂(R9-CHAP-CBD，R9-M23-CBD，TAT-Ami-CBD，TAT-CHAP-CBD和TAT-M23-CBD)。所有数据都根据先前在WO2013/169104中的描述收集于以100nM蛋白浓度(除了使用1μM的Ami-CBD构建体之外)对金黄色葡萄球菌SA113底物细胞的浊度降低测试中。图7a至图7e描绘了构建体的性能。正如从图7a至图7e可以看出，通常而言，当对金黄色葡萄球菌细胞进行分析时，N-端CPP标记的蛋白是有活性的，但与未标记或C-端标记的变体相比却表现出较低活性。为了分析细胞内杀灭的效率，所述构建体应该如实施例3一样在细胞内金黄色葡萄球菌杀伤测试中进行测试。
参考文献
1.Dantes，R.，et al.National burden of invasive methicillin-resistantStaphylococcus aureus infections，United Stares，2011.JAMA internal medicine173，1970-1978(2013).
2.Fowler，V.G.，Jr.，et al.Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunctionand low-level in vitro resistance to thrombin-induced platelet microbicidalprotein.The Journal of infectious diseases 190，1140-1149(2004).
3.Welsh，K.J.，et al.Predictors of relapse of methicillin-resistantStaphylococcus aureus bacteremia after treatment with vancomycin.Journal ofclinical microbiology 49，3669-3672(2011).
4.Libraty，D.H.，Patkar，C.&Torres，B.Staphylococcus aureus reactivationosteomyelitis after 75 years.The New England journal of medicine 366，481-482(2012).
5.Proctor，R.A.，et al.Small colony variants：a pathogenic form ofbacteria that facilitates persistent and recurrent infections.Nat RevMicrobiol 4，295-305(2006).
6.Proctor，R.A.，van Langevelde，P.，Kristjansson，M.，Maslow，J.N.&Arbeit，R.D.Persistent and relapsing infections associated with small-colony variantsof Staphylococcus aureus.Clinical infectious diseases：an official publicationof the Infectious Diseases Society of America 20，95-102(1995).
7.Conlon，B.P.Staphylococcus aureus chronic and relapsing infections：Evidence of a role for persister cells：An investigation of persister cells，their formation and their role in S.aureus disease.BioEssays：news and reviewsin molecular，cellular and developmental biology 36，991-996(2014).
8.Fauvart，M.，De Groote，V.N.&Michiels，J.Role of persister cells inchronic infections：clinical relevance and perspectives on anti-persistertherapies.Journal of medical microbiology 60，699-709(2011).
9.Conlon，B.P.，et al.Activated ClpP kills persisters and eradicares achronic biofilm infection.Naturc 503，365-370(2013).
10.Lechner，S.，Lewis，K.&Bertram，R.Staphylococcus aureus persisterstolerant to bactericidal antibiotics.Journal of molecular microbiology andbiotechnology 22，235-244(2012).
11.Kaiser，P.，et al.Cecum lymph node dendritic cells harbor slow-growing bactcria phenotypically tolerant to antibiotic treatment.PLoS biology12，e1001793(2014).
12.Singh，R.，Ray，P.，Das，A.&Sharma，M.Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associatedStaphylococcus aureus：an in vitro study.Journal of medical microbiology 58，1067-1073(2009).
13.Garcia，L.G.，et al.Antibiotic activity against small-colonyvariants of Staphylococcus aureus：review of in vitro，animal and clinicaldata.The Journal of antimicrobial chemotherapy 68，1455-1464(2013).
14.Tuchscherr，L.，et al.Staphyloeoccus aureus phenotype switching：aneffective bacterial strategy to escape host immune response and establish achronic infection.Embo Molecular Medicine 3，129-141(2011).
15.Vesga，O.，et al.Staphylococcus aureus small colony variants areinduced by the endothelial cell intracellular milieu.J Infect Dis173，739-742(1996).
16.Tuchscherr，L.，et al.Staphylococcus aureus small-colony variantsare adapted phenotypes for intracellular persistence.The Journal ofinfectious diseases 202，1031-1040(2010).
17.Baudoux，P.，et al.Combined effect of pH and concentration on theactivities of gentamicin326and oxacillin against Staphylococcus aureus inpharmacodynamic models of extracellular and intracellular infections.TheJournal of antimicrobial chemotherapy59，246-253(2007).
18.Lam，C.&Mathison，G.E.Effect of low intraphagolysosomal pH onantimicrobial activity of antibiotics against ingested staphylococci.Journalof medical microbiology16，309-316(1983).
19.Nguyen，H.A.，et al.Factors influencing the intracellular activityof fluoroquinolones：a study using levo floxacin in a Staphylococcus aureusTHP-1 monocyte model.The Journal of antimicrobial chemotherapy 57，883-890(2006).
20.Barcia-Macay，M.，Seral，C.，Mingeot-Leclercq，M.P.，Tulkens，P.M.&VanBambeke，F.Pharmacodynamic evaluation of the intracellular activities ofantibiotics against Staphylococcus aureus in a model of THP-1macrophages.Antimicrobial agents and chemotherapy 50，841-851(2006).
21.Lebeaux，D.，et al.pH-mediated potentiation of aminoglycosides killsbacterial persisters and eradicatcs in vivo biofilms.The Journal ofinfectious diseascs 210，1357-1366(2014).
22.Schroeder，A.，Kland，R.，Peschel，A.，von 340 Eiff，C.&Aepfelbacher，M.Live cell imaging of phagosome maturation in Staphylococcus aureus infectedhuman endothelial cells：small colony variants are able to survive inlysosomes.Medical Microbiology and Immunology 195，185-194(2006).
23.Kahl，B.C.，et al.Thymidine-dependent Staphylococcus aureus small-colony variants are associated with extensive alterations in regulator andvirulence gene expression profiles.Infect Immun 73，4119-4126(2005).
24.Parret，A.H.et al.Bacteria killing their own kind：novelbacteriocins of Pseudomonas and other γ-proteobacteria.Trends inMicrobiology 10，107-112(2002)
25.Naz S.A.ct al.Biophysicochemical characterization of Pyocin SA 189produced by Pseudomonas aeruginosa SA 189.Brazilian Journal of Microbiology46，1147-1154(2015).
序列表
<110> 迈克瑞欧斯人体健康有限公司
<120> 治疗细菌感染的方法
<130> P6054982PCT
<150> 15158880.3
<151> 2015-03-12
<150> EP15158880.3
<151> 2015-03-12
<160> 108
<170> PatentIn version 3.5
<210> 1
<211> 180
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 1
Met Leu Lys His Ile Tyr Ser Asn His Ile Lys Gly Asn Lys Ile Thr
1 5 10 15
Ala Pro Lys Pro Ser Ile Gln Gly Val Val Ile His Asn Asp Tyr Gly
20 25 30
Ser Met Thr Pro Ser Gln Tyr Leu Pro Trp Leu Tyr Ala Arg Glu Asn
35 40 45
Asn Gly Thr His Val Asn Gly Trp Ala Ser Val Tyr Ala Asn Arg Asn
50 55 60
Glu Val Leu Trp Tyr His Pro Thr Asp Tyr Val Glu Trp His Cys Gly
65 70 75 80
Asn Gln Trp Ala Asn Ala Asn Leu Ile Gly Phe Glu Val Cys Glu Ser
85 90 95
Tyr Pro Gly Arg Ile Ser Asp Lys Leu Phe Leu Glu Asn Glu Glu Ala
100 105 110
Thr Leu Lys Val Ala Ala Asp Val Met Lys Ser Tyr Gly Leu Pro Val
115 120 125
Asn Arg Asn Thr Val Arg Leu His Asn Glu Phe Phe Gly Thr Ser Cys
130 135 140
Pro His Arg Ser Trp Asp Leu His Val Gly Lys Gly Glu Pro Tyr Thr
145 150 155 160
Thr Thr Asn Ile Asn Lys Met Lys Asp Tyr Phe Ile Lys Arg Ile Lys
165 170 175
His Tyr Tyr Asp
180
<210> 2
<211> 141
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 2
Ala Ala Thr His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys Lys
1 5 10 15
Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met His
20 25 30
Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala Ile
35 40 45
Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly Gly
50 55 60
Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp Tyr
65 70 75 80
Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys Ala
85 90 95
Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala Pro
100 105 110
His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr Ala
115 120 125
Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly
130 135 140
<210> 3
<211> 161
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 3
Met Ser Ile Ile Met Glu Val Ala Thr Met Gln Ala Lys Leu Thr Lys
1 5 10 15
Asn Glu Phe Ile Glu Trp Leu Lys Thr Ser Glu Gly Lys Gln Phe Asn
20 25 30
Val Asp Leu Trp Tyr Gly Phe Gln Cys Phe Asp Tyr Ala Asn Ala Gly
35 40 45
Trp Lys Val Leu Phe Gly Leu Leu Leu Lys Gly Leu Gly Ala Lys Asp
50 55 60
Ile Pro Phe Ala Asn Asn Phe Asp Gly Leu Ala Thr Val Tyr Gln Asn
65 70 75 80
Thr Pro Asp Phe Leu Ala Gln Pro Gly Asp Met Val Val Phe Gly Ser
85 90 95
Asn Tyr Gly Ala Gly Tyr Gly His Val Ala Trp Val Ile Glu Ala Thr
100 105 110
Leu Asp Tyr Ile Ile Val Tyr Glu Gln Asn Trp Leu Gly Gly Gly Trp
115 120 125
Thr Asp Gly Ile Glu Gln Pro Gly Trp Gly Trp Glu Lys Val Thr Arg
130 135 140
Arg Gln His Ala Tyr Asp Phe Pro Met Trp Phe Ile Arg Pro Asn Phe
145 150 155 160
Lys
<210> 4
<211> 145
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 4
Met Lys Thr Leu Lys Gln Ala Glu Ser Tyr Ile Lys Ser Lys Val Asn
1 5 10 15
Thr Gly Thr Asp Phe Asp Gly Leu Tyr Gly Tyr Gln Cys Met Asp Leu
20 25 30
Ala Val Asp Tyr Ile Tyr His Val Thr Asp Gly Lys Ile Arg Met Trp
35 40 45
Gly Asn Ala Lys Asp Ala Ile Asn Asn Ser Phe Gly Gly Thr Ala Thr
50 55 60
Val Tyr Lys Asn Tyr Pro Ala Phe Arg Pro Lys Tyr Gly Asp Val Val
65 70 75 80
Val Trp Thr Thr Gly Asn Phe Ala Thr Tyr Gly His Ile Ala Ile Val
85 90 95
Thr Asn Pro Asp Pro Tyr Gly Asp Leu Gln Tyr Val Thr Val Leu Glu
100 105 110
Gln Asn Trp Asn Gly Asn Gly Ile Tyr Lys Thr Glu Leu Ala Thr Ile
115 120 125
Arg Thr His Asp Tyr Thr Gly Ile Thr His Phe Ile Arg Pro Asn Phe
130 135 140
Ala
145
<210> 5
<211> 151
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 5
Met Gly Leu Pro Ser Pro Lys Lys Arg Lys Pro Thr Ala Ser Glu Val
1 5 10 15
Ala Ala Trp Ala Lys Arg Met Ile Gly Arg Arg Val Asp Val Asp Gly
20 25 30
Tyr His Gly Ala Gln Cys Trp Asp Leu Pro Asn Tyr Ile Phe Asn Arg
35 40 45
Tyr Trp His Phe Lys Thr Thr Gly Asn Ala Ile Ala Met Ala Trp Tyr
50 55 60
Arg Tyr Pro Lys Gly Phe Lys Phe Tyr Arg Asn Thr Arg Asn Phe Val
65 70 75 80
Pro Lys Pro Gly Asp Met Ala Val Trp Gly Lys Gly Ser Phe Asn Asn
85 90 95
Gly Val Gly His Thr Ala Val Val Ile Gly Pro Ser Thr Lys Ser Tyr
100 105 110
Phe Thr Ser Val Asp Gln Asn Trp Ile Gly Ala Asn Ser Tyr Thr Gly
115 120 125
Ser Pro Gly Ala Lys Ile Lys His Ser Tyr Asn Gly Ile Ser Gly Phe
130 135 140
Val Arg Pro Pro Tyr His Ala
145 150
<210> 6
<211> 147
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 6
Met Ala Leu Pro Lys Thr Gly Lys Pro Thr Ala Lys Gln Val Val Asp
1 5 10 15
Trp Ala Ile Asn Leu Ile Gly Ser Gly Val Asp Val Asp Gly Tyr Tyr
20 25 30
Gly Arg Gln Cys Trp Asp Leu Pro Asn Tyr Ile Phe Asn Arg Tyr Trp
35 40 45
Asn Phe Lys Thr Pro Gly Asn Ala Arg Asp Met Ala Trp Tyr Arg Tyr
50 55 60
Pro Glu Gly Phe Lys Val Phe Arg Asn Thr Ser Asp Phe Val Pro Lys
65 70 75 80
Pro Gly Asp Ile Ala Val Trp Thr Gly Gly Asn Tyr Asn Trp Asn Thr
85 90 95
Trp Gly His Thr Gly Ile Val Val Gly Pro Ser Thr Lys Ser Tyr Phe
100 105 110
Tyr Ser Val Asp Gln Asn Trp Asn Asn Ser Asn Ser Tyr Val Gly Ser
115 120 125
Pro Ala Ala Lys Ile Lys His Ser Tyr Phe Gly Val Thr His Phe Val
130 135 140
Arg Pro Ala
145
<210> 7
<211> 165
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 7
Met Ala Lys Thr Gln Ala Glu Ile Asn Lys Arg Leu Asp Ala Tyr Ala
1 5 10 15
Lys Gly Thr Val Asp Ser Pro Tyr Arg Ile Lys Lys Ala Thr Ser Tyr
20 25 30
Asp Pro Ser Phe Gly Val Met Glu Ala Gly Ala Ile Asp Ala Asp Gly
35 40 45
Tyr Tyr His Ala Gln Cys Gln Asp Leu Ile Thr Asp Tyr Val Leu Trp
50 55 60
Leu Thr Asp Asn Lys Val Arg Thr Trp Gly Asn Ala Lys Asp Gln Ile
65 70 75 80
Lys Gln Ser Tyr Gly Thr Gly Phe Lys Ile His Glu Asn Lys Pro Ser
85 90 95
Thr Val Pro Lys Lys Gly Trp Ile Ala Val Phe Thr Ser Gly Ser Tyr
100 105 110
Gln Gln Trp Gly His Ile Gly Ile Val Tyr Asp Gly Gly Asn Thr Ser
115 120 125
Thr Phe Thr Ile Leu Glu Gln Asn Trp Asn Gly Tyr Ala Asn Lys Lys
130 135 140
Pro Thr Lys Arg Val Asp Asn Tyr Tyr Gly Leu Thr His Phe Ile Glu
145 150 155 160
Ile Pro Val Lys Ala
165
<210> 8
<211> 128
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 8
Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser Asp
1 5 10 15
Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys Ala
20 25 30
Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu His
35 40 45
Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr Lys
50 55 60
Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly Gln
65 70 75 80
Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp Val
85 90 95
Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg Thr
100 105 110
Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile Lys
115 120 125
<210> 9
<211> 78
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 9
Ala Pro Lys Ser Lys Pro Ser Lys Ile Lys Thr Thr Trp Asn Trp Gly
1 5 10 15
Gly Lys Phe Thr Ala Asn Ser Thr Ile Lys Val Arg Lys Ser Pro Gly
20 25 30
Leu Lys Gly Ile Val Val Glu Ser Gly Ser Trp Leu Tyr Lys Gly Asn
35 40 45
Tyr Val Pro Phe Asp Gln Val Ile Lys Lys Asp Gly Tyr Trp Trp Ile
50 55 60
Arg Phe Lys Tyr Val Gln Pro Gly Ser Ser Asn Lys His Phe
65 70 75
<210> 10
<211> 92
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 10
Trp Lys Thr Asn Lys Tyr Gly Thr Leu Tyr Lys Ser Glu Ser Ala Ser
1 5 10 15
Phe Thr Pro Asn Thr Asp Ile Ile Thr Arg Thr Thr Gly Pro Phe Arg
20 25 30
Ser Met Pro Gln Ser Gly Val Leu Lys Ala Gly Gln Thr Ile His Tyr
35 40 45
Asp Glu Val Met Lys Gln Asp Gly His Val Trp Val Gly Tyr Thr Gly
50 55 60
Asn Ser Gly Gln Arg Ile Tyr Leu Pro Val Arg Thr Trp Asn Lys Ser
65 70 75 80
Thr Asn Thr Leu Gly Val Leu Trp Gly Thr Ile Lys
85 90
<210> 11
<211> 92
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 11
Tyr Lys Thr Asn Lys Tyr Gly Thr Leu Tyr Lys Ser Glu Ser Ala Ser
1 5 10 15
Phe Thr Ala Asn Thr Asp Ile Ile Thr Arg Leu Thr Gly Pro Phe Arg
20 25 30
Ser Met Pro Gln Ser Gly Val Leu Arg Lys Gly Leu Thr Ile Lys Tyr
35 40 45
Asp Glu Val Met Lys Gln Asp Gly His Val Trp Val Gly Tyr Asn Thr
50 55 60
Asn Ser Gly Lys Arg Val Tyr Leu Pro Val Arg Thr Trp Asn Glu Ser
65 70 75 80
Thr Gly Glu Leu Gly Pro Leu Trp Gly Thr Ile Lys
85 90
<210> 12
<211> 30
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 12
Trp Glu Ala Lys Leu Ala Lys Ala Leu Ala Lys Ala Leu Ala Lys His
1 5 10 15
Leu Ala Lys Ala Leu Ala Lys Ala Leu Lys Ala Cys Glu Ala
20 25 30
<210> 13
<211> 22
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 13
Met Val Thr Val Leu Phe Arg Arg Leu Arg Ile Arg Arg Ala Ser Gly
1 5 10 15
Pro Pro Arg Val Arg Val
20
<210> 14
<211> 18
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 14
Lys Leu Ala Leu Lys Leu Ala Leu Lys Ala Leu Lys Ala Ala Leu Lys
1 5 10 15
Leu Ala
<210> 15
<211> 27
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> GALFLGFLGAAGSTMGAWSQPKKKRKV
<400> 15
Gly Ala Leu Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly
1 5 10 15
Ala Trp Ser Gln Pro Lys Lys Lys Arg Lys Val
20 25
<210> 16
<211> 16
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 16
Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys
1 5 10 15
<210> 17
<211> 21
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 17
Lys Glu Thr Trp Trp Glu Thr Trp Trp Thr Glu Trp Ser Gln Pro Lys
1 5 10 15
Lys Lys Arg Lys Val
20
<210> 18
<211> 12
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 18
Arg Arg Gln Arg Arg Thr Ser Lys Leu Met Lys Arg
1 5 10
<210> 19
<211> 18
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 19
Leu Leu Ile Ile Leu Arg Arg Arg Ile Arg Lys Gln Ala His Ala His
1 5 10 15
Ser Lys
<210> 20
<211> 9
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 20
Arg Arg Trp Trp Arg Arg Trp Arg Arg
1 5
<210> 21
<211> 16
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段包含 6 至15 个R残基
<400> 21
Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg
1 5 10 15
<210> 22
<211> 13
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 22
Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Pro Gln
1 5 10
<210> 23
<211> 9
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 23
Arg Lys Lys Arg Arg Gln Arg Arg Arg
1 5
<210> 24
<211> 27
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 24
Gly Trp Thr Leu Asn Ser Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu
1 5 10 15
Lys Ala Leu Ala Ala Leu Ala Lys Lys Ile Leu
20 25
<210> 25
<211> 21
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 25
Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu Lys Ala Leu Ala Ala Leu
1 5 10 15
Ala Lys Lys Ile Leu
20
<210> 26
<400> 26
000
<210> 27
<211> 269
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 27
Met Ala Ala Thr His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys
1 5 10 15
Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met
20 25 30
His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala
35 40 45
Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly
50 55 60
Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp
65 70 75 80
Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys
85 90 95
Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala
100 105 110
Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr
115 120 125
Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Gly Lys
130 135 140
Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser Asp Val Lys Gln
145 150 155 160
Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys Ala Thr Asp Trp
165 170 175
Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu His Ala Ser Phe
180 185 190
Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr Lys Gly Pro Trp
195 200 205
Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly Gln Thr Ile Lys
210 215 220
Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp Val Ser Trp Glu
225 230 235 240
Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg Thr Trp Asp Ala
245 250 255
Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile Lys
260 265
<210> 28
<211> 289
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 28
Met Ser Ile Ile Met Glu Val Ala Thr Met Gln Ala Lys Leu Thr Lys
1 5 10 15
Asn Glu Phe Ile Glu Trp Leu Lys Thr Ser Glu Gly Lys Gln Phe Asn
20 25 30
Val Asp Leu Trp Tyr Gly Phe Gln Cys Phe Asp Tyr Ala Asn Ala Gly
35 40 45
Trp Lys Val Leu Phe Gly Leu Leu Leu Lys Gly Leu Gly Ala Lys Asp
50 55 60
Ile Pro Phe Ala Asn Asn Phe Asp Gly Leu Ala Thr Val Tyr Gln Asn
65 70 75 80
Thr Pro Asp Phe Leu Ala Gln Pro Gly Asp Met Val Val Phe Gly Ser
85 90 95
Asn Tyr Gly Ala Gly Tyr Gly His Val Ala Trp Val Ile Glu Ala Thr
100 105 110
Leu Asp Tyr Ile Ile Val Tyr Glu Gln Asn Trp Leu Gly Gly Gly Trp
115 120 125
Thr Asp Gly Ile Glu Gln Pro Gly Trp Gly Trp Glu Lys Val Thr Arg
130 135 140
Arg Gln His Ala Tyr Asp Phe Pro Met Trp Phe Ile Arg Pro Asn Phe
145 150 155 160
Lys Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser
165 170 175
Asp Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys
180 185 190
Ala Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu
195 200 205
His Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr
210 215 220
Lys Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly
225 230 235 240
Gln Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp
245 250 255
Val Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg
260 265 270
Thr Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile
275 280 285
Lys
<210> 29
<211> 308
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 29
Met Leu Lys His Ile Tyr Ser Asn His Ile Lys Gly Asn Lys Ile Thr
1 5 10 15
Ala Pro Lys Pro Ser Ile Gln Gly Val Val Ile His Asn Asp Tyr Gly
20 25 30
Ser Met Thr Pro Ser Gln Tyr Leu Pro Trp Leu Tyr Ala Arg Glu Asn
35 40 45
Asn Gly Thr His Val Asn Gly Trp Ala Ser Val Tyr Ala Asn Arg Asn
50 55 60
Glu Val Leu Trp Tyr His Pro Thr Asp Tyr Val Glu Trp His Cys Gly
65 70 75 80
Asn Gln Trp Ala Asn Ala Asn Leu Ile Gly Phe Glu Val Cys Glu Ser
85 90 95
Tyr Pro Gly Arg Ile Ser Asp Lys Leu Phe Leu Glu Asn Glu Glu Ala
100 105 110
Thr Leu Lys Val Ala Ala Asp Val Met Lys Ser Tyr Gly Leu Pro Val
115 120 125
Asn Arg Asn Thr Val Arg Leu His Asn Glu Phe Phe Gly Thr Ser Cys
130 135 140
Pro His Arg Ser Trp Asp Leu His Val Gly Lys Gly Glu Pro Tyr Thr
145 150 155 160
Thr Thr Asn Ile Asn Lys Met Lys Asp Tyr Phe Ile Lys Arg Ile Lys
165 170 175
His Tyr Tyr Asp Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile
180 185 190
Lys Gln Ser Asp Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln
195 200 205
Ile Val Lys Ala Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr
210 215 220
Lys Ala Glu His Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile
225 230 235 240
Thr Arg Tyr Lys Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu
245 250 255
Gln Lys Gly Gln Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly
260 265 270
His Val Trp Val Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met
275 280 285
Pro Val Arg Thr Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp
290 295 300
Gly Glu Ile Lys
305
<210> 30
<211> 326
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 30
Met Leu Lys His Ile Tyr Ser Asn His Ile Lys Gly Asn Lys Ile Thr
1 5 10 15
Ala Pro Lys Pro Ser Ile Gln Gly Val Val Ile His Asn Asp Tyr Gly
20 25 30
Ser Met Thr Pro Ser Gln Tyr Leu Pro Trp Leu Tyr Ala Arg Glu Asn
35 40 45
Asn Gly Thr His Val Asn Gly Trp Ala Ser Val Tyr Ala Asn Arg Asn
50 55 60
Glu Val Leu Trp Tyr His Pro Thr Asp Tyr Val Glu Trp His Cys Gly
65 70 75 80
Asn Gln Trp Ala Asn Ala Asn Leu Ile Gly Phe Glu Val Cys Glu Ser
85 90 95
Tyr Pro Gly Arg Ile Ser Asp Lys Leu Phe Leu Glu Asn Glu Glu Ala
100 105 110
Thr Leu Lys Val Ala Ala Asp Val Met Lys Ser Tyr Gly Leu Pro Val
115 120 125
Asn Arg Asn Thr Val Arg Leu His Asn Glu Phe Phe Gly Thr Ser Cys
130 135 140
Pro His Arg Ser Trp Asp Leu His Val Gly Lys Gly Glu Pro Tyr Thr
145 150 155 160
Thr Thr Asn Ile Asn Lys Met Lys Asp Tyr Phe Ile Lys Arg Ile Lys
165 170 175
His Tyr Tyr Asp Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile
180 185 190
Lys Gln Ser Asp Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln
195 200 205
Ile Val Lys Ala Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr
210 215 220
Lys Ala Glu His Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile
225 230 235 240
Thr Arg Tyr Lys Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu
245 250 255
Gln Lys Gly Gln Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly
260 265 270
His Val Trp Val Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met
275 280 285
Pro Val Arg Thr Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp
290 295 300
Gly Glu Ile Lys Glu Leu Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg
305 310 315 320
Arg Met Lys Trp Lys Lys
325
<210> 31
<211> 319
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 31
Met Leu Lys His Ile Tyr Ser Asn His Ile Lys Gly Asn Lys Ile Thr
1 5 10 15
Ala Pro Lys Pro Ser Ile Gln Gly Val Val Ile His Asn Asp Tyr Gly
20 25 30
Ser Met Thr Pro Ser Gln Tyr Leu Pro Trp Leu Tyr Ala Arg Glu Asn
35 40 45
Asn Gly Thr His Val Asn Gly Trp Ala Ser Val Tyr Ala Asn Arg Asn
50 55 60
Glu Val Leu Trp Tyr His Pro Thr Asp Tyr Val Glu Trp His Cys Gly
65 70 75 80
Asn Gln Trp Ala Asn Ala Asn Leu Ile Gly Phe Glu Val Cys Glu Ser
85 90 95
Tyr Pro Gly Arg Ile Ser Asp Lys Leu Phe Leu Glu Asn Glu Glu Ala
100 105 110
Thr Leu Lys Val Ala Ala Asp Val Met Lys Ser Tyr Gly Leu Pro Val
115 120 125
Asn Arg Asn Thr Val Arg Leu His Asn Glu Phe Phe Gly Thr Ser Cys
130 135 140
Pro His Arg Ser Trp Asp Leu His Val Gly Lys Gly Glu Pro Tyr Thr
145 150 155 160
Thr Thr Asn Ile Asn Lys Met Lys Asp Tyr Phe Ile Lys Arg Ile Lys
165 170 175
His Tyr Tyr Asp Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile
180 185 190
Lys Gln Ser Asp Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln
195 200 205
Ile Val Lys Ala Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr
210 215 220
Lys Ala Glu His Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile
225 230 235 240
Thr Arg Tyr Lys Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu
245 250 255
Gln Lys Gly Gln Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly
260 265 270
His Val Trp Val Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met
275 280 285
Pro Val Arg Thr Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp
290 295 300
Gly Glu Ile Lys Glu Leu Arg Arg Arg Arg Arg Arg Arg Arg Arg
305 310 315
<210> 32
<211> 323
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 32
Met Leu Lys His Ile Tyr Ser Asn His Ile Lys Gly Asn Lys Ile Thr
1 5 10 15
Ala Pro Lys Pro Ser Ile Gln Gly Val Val Ile His Asn Asp Tyr Gly
20 25 30
Ser Met Thr Pro Ser Gln Tyr Leu Pro Trp Leu Tyr Ala Arg Glu Asn
35 40 45
Asn Gly Thr His Val Asn Gly Trp Ala Ser Val Tyr Ala Asn Arg Asn
50 55 60
Glu Val Leu Trp Tyr His Pro Thr Asp Tyr Val Glu Trp His Cys Gly
65 70 75 80
Asn Gln Trp Ala Asn Ala Asn Leu Ile Gly Phe Glu Val Cys Glu Ser
85 90 95
Tyr Pro Gly Arg Ile Ser Asp Lys Leu Phe Leu Glu Asn Glu Glu Ala
100 105 110
Thr Leu Lys Val Ala Ala Asp Val Met Lys Ser Tyr Gly Leu Pro Val
115 120 125
Asn Arg Asn Thr Val Arg Leu His Asn Glu Phe Phe Gly Thr Ser Cys
130 135 140
Pro His Arg Ser Trp Asp Leu His Val Gly Lys Gly Glu Pro Tyr Thr
145 150 155 160
Thr Thr Asn Ile Asn Lys Met Lys Asp Tyr Phe Ile Lys Arg Ile Lys
165 170 175
His Tyr Tyr Asp Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile
180 185 190
Lys Gln Ser Asp Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln
195 200 205
Ile Val Lys Ala Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr
210 215 220
Lys Ala Glu His Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile
225 230 235 240
Thr Arg Tyr Lys Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu
245 250 255
Gln Lys Gly Gln Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly
260 265 270
His Val Trp Val Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met
275 280 285
Pro Val Arg Thr Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp
290 295 300
Gly Glu Ile Lys Glu Leu Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg
305 310 315 320
Pro Pro Gln
<210> 33
<211> 199
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 33
Met Leu Lys His Ile Tyr Ser Asn His Ile Lys Gly Asn Lys Ile Thr
1 5 10 15
Ala Pro Lys Pro Ser Ile Gln Gly Val Val Ile His Asn Asp Tyr Gly
20 25 30
Ser Met Thr Pro Ser Gln Tyr Leu Pro Trp Leu Tyr Ala Arg Glu Asn
35 40 45
Asn Gly Thr His Val Asn Gly Trp Ala Ser Val Tyr Ala Asn Arg Asn
50 55 60
Glu Val Leu Trp Tyr His Pro Thr Asp Tyr Val Glu Trp His Cys Gly
65 70 75 80
Asn Gln Trp Ala Asn Ala Asn Leu Ile Gly Phe Glu Val Cys Glu Ser
85 90 95
Tyr Pro Gly Arg Ile Ser Asp Lys Leu Phe Leu Glu Asn Glu Glu Ala
100 105 110
Thr Leu Lys Val Ala Ala Asp Val Met Lys Ser Tyr Gly Leu Pro Val
115 120 125
Asn Arg Asn Thr Val Arg Leu His Asn Glu Phe Phe Gly Thr Ser Cys
130 135 140
Pro His Arg Ser Trp Asp Leu His Val Gly Lys Gly Glu Pro Tyr Thr
145 150 155 160
Thr Thr Asn Ile Asn Lys Met Lys Asp Tyr Phe Ile Lys Arg Ile Lys
165 170 175
His Tyr Tyr Asp Gly Glu Leu Arg Gln Ile Lys Ile Trp Phe Gln Asn
180 185 190
Arg Arg Met Lys Trp Lys Lys
195
<210> 34
<211> 192
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 34
Met Leu Lys His Ile Tyr Ser Asn His Ile Lys Gly Asn Lys Ile Thr
1 5 10 15
Ala Pro Lys Pro Ser Ile Gln Gly Val Val Ile His Asn Asp Tyr Gly
20 25 30
Ser Met Thr Pro Ser Gln Tyr Leu Pro Trp Leu Tyr Ala Arg Glu Asn
35 40 45
Asn Gly Thr His Val Asn Gly Trp Ala Ser Val Tyr Ala Asn Arg Asn
50 55 60
Glu Val Leu Trp Tyr His Pro Thr Asp Tyr Val Glu Trp His Cys Gly
65 70 75 80
Asn Gln Trp Ala Asn Ala Asn Leu Ile Gly Phe Glu Val Cys Glu Ser
85 90 95
Tyr Pro Gly Arg Ile Ser Asp Lys Leu Phe Leu Glu Asn Glu Glu Ala
100 105 110
Thr Leu Lys Val Ala Ala Asp Val Met Lys Ser Tyr Gly Leu Pro Val
115 120 125
Asn Arg Asn Thr Val Arg Leu His Asn Glu Phe Phe Gly Thr Ser Cys
130 135 140
Pro His Arg Ser Trp Asp Leu His Val Gly Lys Gly Glu Pro Tyr Thr
145 150 155 160
Thr Thr Asn Ile Asn Lys Met Lys Asp Tyr Phe Ile Lys Arg Ile Lys
165 170 175
His Tyr Tyr Asp Gly Glu Leu Arg Arg Arg Arg Arg Arg Arg Arg Arg
180 185 190
<210> 35
<211> 196
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 35
Met Leu Lys His Ile Tyr Ser Asn His Ile Lys Gly Asn Lys Ile Thr
1 5 10 15
Ala Pro Lys Pro Ser Ile Gln Gly Val Val Ile His Asn Asp Tyr Gly
20 25 30
Ser Met Thr Pro Ser Gln Tyr Leu Pro Trp Leu Tyr Ala Arg Glu Asn
35 40 45
Asn Gly Thr His Val Asn Gly Trp Ala Ser Val Tyr Ala Asn Arg Asn
50 55 60
Glu Val Leu Trp Tyr His Pro Thr Asp Tyr Val Glu Trp His Cys Gly
65 70 75 80
Asn Gln Trp Ala Asn Ala Asn Leu Ile Gly Phe Glu Val Cys Glu Ser
85 90 95
Tyr Pro Gly Arg Ile Ser Asp Lys Leu Phe Leu Glu Asn Glu Glu Ala
100 105 110
Thr Leu Lys Val Ala Ala Asp Val Met Lys Ser Tyr Gly Leu Pro Val
115 120 125
Asn Arg Asn Thr Val Arg Leu His Asn Glu Phe Phe Gly Thr Ser Cys
130 135 140
Pro His Arg Ser Trp Asp Leu His Val Gly Lys Gly Glu Pro Tyr Thr
145 150 155 160
Thr Thr Asn Ile Asn Lys Met Lys Asp Tyr Phe Ile Lys Arg Ile Lys
165 170 175
His Tyr Tyr Asp Gly Glu Leu Gly Arg Lys Lys Arg Arg Gln Arg Arg
180 185 190
Arg Pro Pro Gln
195
<210> 36
<211> 307
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 36
Met Ser Ile Ile Met Glu Val Ala Thr Met Gln Ala Lys Leu Thr Lys
1 5 10 15
Asn Glu Phe Ile Glu Trp Leu Lys Thr Ser Glu Gly Lys Gln Phe Asn
20 25 30
Val Asp Leu Trp Tyr Gly Phe Gln Cys Phe Asp Tyr Ala Asn Ala Gly
35 40 45
Trp Lys Val Leu Phe Gly Leu Leu Leu Lys Gly Leu Gly Ala Lys Asp
50 55 60
Ile Pro Phe Ala Asn Asn Phe Asp Gly Leu Ala Thr Val Tyr Gln Asn
65 70 75 80
Thr Pro Asp Phe Leu Ala Gln Pro Gly Asp Met Val Val Phe Gly Ser
85 90 95
Asn Tyr Gly Ala Gly Tyr Gly His Val Ala Trp Val Ile Glu Ala Thr
100 105 110
Leu Asp Tyr Ile Ile Val Tyr Glu Gln Asn Trp Leu Gly Gly Gly Trp
115 120 125
Thr Asp Gly Ile Glu Gln Pro Gly Trp Gly Trp Glu Lys Val Thr Arg
130 135 140
Arg Gln His Ala Tyr Asp Phe Pro Met Trp Phe Ile Arg Pro Asn Phe
145 150 155 160
Lys Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser
165 170 175
Asp Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys
180 185 190
Ala Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu
195 200 205
His Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr
210 215 220
Lys Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly
225 230 235 240
Gln Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp
245 250 255
Val Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg
260 265 270
Thr Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile
275 280 285
Lys Glu Leu Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys
290 295 300
Trp Lys Lys
305
<210> 37
<211> 300
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 37
Met Ser Ile Ile Met Glu Val Ala Thr Met Gln Ala Lys Leu Thr Lys
1 5 10 15
Asn Glu Phe Ile Glu Trp Leu Lys Thr Ser Glu Gly Lys Gln Phe Asn
20 25 30
Val Asp Leu Trp Tyr Gly Phe Gln Cys Phe Asp Tyr Ala Asn Ala Gly
35 40 45
Trp Lys Val Leu Phe Gly Leu Leu Leu Lys Gly Leu Gly Ala Lys Asp
50 55 60
Ile Pro Phe Ala Asn Asn Phe Asp Gly Leu Ala Thr Val Tyr Gln Asn
65 70 75 80
Thr Pro Asp Phe Leu Ala Gln Pro Gly Asp Met Val Val Phe Gly Ser
85 90 95
Asn Tyr Gly Ala Gly Tyr Gly His Val Ala Trp Val Ile Glu Ala Thr
100 105 110
Leu Asp Tyr Ile Ile Val Tyr Glu Gln Asn Trp Leu Gly Gly Gly Trp
115 120 125
Thr Asp Gly Ile Glu Gln Pro Gly Trp Gly Trp Glu Lys Val Thr Arg
130 135 140
Arg Gln His Ala Tyr Asp Phe Pro Met Trp Phe Ile Arg Pro Asn Phe
145 150 155 160
Lys Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser
165 170 175
Asp Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys
180 185 190
Ala Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu
195 200 205
His Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr
210 215 220
Lys Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly
225 230 235 240
Gln Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp
245 250 255
Val Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg
260 265 270
Thr Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile
275 280 285
Lys Glu Leu Arg Arg Arg Arg Arg Arg Arg Arg Arg
290 295 300
<210> 38
<211> 304
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 38
Met Ser Ile Ile Met Glu Val Ala Thr Met Gln Ala Lys Leu Thr Lys
1 5 10 15
Asn Glu Phe Ile Glu Trp Leu Lys Thr Ser Glu Gly Lys Gln Phe Asn
20 25 30
Val Asp Leu Trp Tyr Gly Phe Gln Cys Phe Asp Tyr Ala Asn Ala Gly
35 40 45
Trp Lys Val Leu Phe Gly Leu Leu Leu Lys Gly Leu Gly Ala Lys Asp
50 55 60
Ile Pro Phe Ala Asn Asn Phe Asp Gly Leu Ala Thr Val Tyr Gln Asn
65 70 75 80
Thr Pro Asp Phe Leu Ala Gln Pro Gly Asp Met Val Val Phe Gly Ser
85 90 95
Asn Tyr Gly Ala Gly Tyr Gly His Val Ala Trp Val Ile Glu Ala Thr
100 105 110
Leu Asp Tyr Ile Ile Val Tyr Glu Gln Asn Trp Leu Gly Gly Gly Trp
115 120 125
Thr Asp Gly Ile Glu Gln Pro Gly Trp Gly Trp Glu Lys Val Thr Arg
130 135 140
Arg Gln His Ala Tyr Asp Phe Pro Met Trp Phe Ile Arg Pro Asn Phe
145 150 155 160
Lys Gly Gly Lys Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser
165 170 175
Asp Val Lys Gln Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys
180 185 190
Ala Thr Asp Trp Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu
195 200 205
His Ala Ser Phe Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr
210 215 220
Lys Gly Pro Trp Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly
225 230 235 240
Gln Thr Ile Lys Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp
245 250 255
Val Ser Trp Glu Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg
260 265 270
Thr Trp Asp Ala Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile
275 280 285
Lys Glu Leu Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Pro Gln
290 295 300
<210> 39
<211> 179
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 39
Met Ser Ile Ile Met Glu Val Ala Thr Met Gln Ala Lys Leu Thr Lys
1 5 10 15
Asn Glu Phe Ile Glu Trp Leu Lys Thr Ser Glu Gly Lys Gln Phe Asn
20 25 30
Val Asp Leu Trp Tyr Gly Phe Gln Cys Phe Asp Tyr Ala Asn Ala Gly
35 40 45
Trp Lys Val Leu Phe Gly Leu Leu Leu Lys Gly Leu Gly Ala Lys Asp
50 55 60
Ile Pro Phe Ala Asn Asn Phe Asp Gly Leu Ala Thr Val Tyr Gln Asn
65 70 75 80
Thr Pro Asp Phe Leu Ala Gln Pro Gly Asp Met Val Val Phe Gly Ser
85 90 95
Asn Tyr Gly Ala Gly Tyr Gly His Val Ala Trp Val Ile Glu Ala Thr
100 105 110
Leu Asp Tyr Ile Ile Val Tyr Glu Gln Asn Trp Leu Gly Gly Gly Trp
115 120 125
Thr Asp Gly Ile Glu Gln Pro Gly Trp Gly Trp Glu Lys Val Thr Arg
130 135 140
Arg Gln His Ala Tyr Asp Phe Pro Met Trp Phe Ile Arg Pro Asn Phe
145 150 155 160
Lys Glu Leu Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys
165 170 175
Trp Lys Lys
<210> 40
<211> 172
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 40
Met Ser Ile Ile Met Glu Val Ala Thr Met Gln Ala Lys Leu Thr Lys
1 5 10 15
Asn Glu Phe Ile Glu Trp Leu Lys Thr Ser Glu Gly Lys Gln Phe Asn
20 25 30
Val Asp Leu Trp Tyr Gly Phe Gln Cys Phe Asp Tyr Ala Asn Ala Gly
35 40 45
Trp Lys Val Leu Phe Gly Leu Leu Leu Lys Gly Leu Gly Ala Lys Asp
50 55 60
Ile Pro Phe Ala Asn Asn Phe Asp Gly Leu Ala Thr Val Tyr Gln Asn
65 70 75 80
Thr Pro Asp Phe Leu Ala Gln Pro Gly Asp Met Val Val Phe Gly Ser
85 90 95
Asn Tyr Gly Ala Gly Tyr Gly His Val Ala Trp Val Ile Glu Ala Thr
100 105 110
Leu Asp Tyr Ile Ile Val Tyr Glu Gln Asn Trp Leu Gly Gly Gly Trp
115 120 125
Thr Asp Gly Ile Glu Gln Pro Gly Trp Gly Trp Glu Lys Val Thr Arg
130 135 140
Arg Gln His Ala Tyr Asp Phe Pro Met Trp Phe Ile Arg Pro Asn Phe
145 150 155 160
Lys Glu Leu Arg Arg Arg Arg Arg Arg Arg Arg Arg
165 170
<210> 41
<211> 176
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 41
Met Ser Ile Ile Met Glu Val Ala Thr Met Gln Ala Lys Leu Thr Lys
1 5 10 15
Asn Glu Phe Ile Glu Trp Leu Lys Thr Ser Glu Gly Lys Gln Phe Asn
20 25 30
Val Asp Leu Trp Tyr Gly Phe Gln Cys Phe Asp Tyr Ala Asn Ala Gly
35 40 45
Trp Lys Val Leu Phe Gly Leu Leu Leu Lys Gly Leu Gly Ala Lys Asp
50 55 60
Ile Pro Phe Ala Asn Asn Phe Asp Gly Leu Ala Thr Val Tyr Gln Asn
65 70 75 80
Thr Pro Asp Phe Leu Ala Gln Pro Gly Asp Met Val Val Phe Gly Ser
85 90 95
Asn Tyr Gly Ala Gly Tyr Gly His Val Ala Trp Val Ile Glu Ala Thr
100 105 110
Leu Asp Tyr Ile Ile Val Tyr Glu Gln Asn Trp Leu Gly Gly Gly Trp
115 120 125
Thr Asp Gly Ile Glu Gln Pro Gly Trp Gly Trp Glu Lys Val Thr Arg
130 135 140
Arg Gln His Ala Tyr Asp Phe Pro Met Trp Phe Ile Arg Pro Asn Phe
145 150 155 160
Lys Glu Leu Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Pro Gln
165 170 175
<210> 42
<211> 287
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 42
Met Ala Ala Thr His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys
1 5 10 15
Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met
20 25 30
His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala
35 40 45
Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly
50 55 60
Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp
65 70 75 80
Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys
85 90 95
Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala
100 105 110
Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr
115 120 125
Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Gly Lys
130 135 140
Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser Asp Val Lys Gln
145 150 155 160
Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys Ala Thr Asp Trp
165 170 175
Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu His Ala Ser Phe
180 185 190
Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr Lys Gly Pro Trp
195 200 205
Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly Gln Thr Ile Lys
210 215 220
Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp Val Ser Trp Glu
225 230 235 240
Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg Thr Trp Asp Ala
245 250 255
Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile Lys Glu Leu Arg
260 265 270
Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys
275 280 285
<210> 43
<211> 280
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 43
Met Ala Ala Thr His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys
1 5 10 15
Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met
20 25 30
His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala
35 40 45
Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly
50 55 60
Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp
65 70 75 80
Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys
85 90 95
Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala
100 105 110
Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr
115 120 125
Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Gly Lys
130 135 140
Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser Asp Val Lys Gln
145 150 155 160
Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys Ala Thr Asp Trp
165 170 175
Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu His Ala Ser Phe
180 185 190
Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr Lys Gly Pro Trp
195 200 205
Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly Gln Thr Ile Lys
210 215 220
Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp Val Ser Trp Glu
225 230 235 240
Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg Thr Trp Asp Ala
245 250 255
Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile Lys Glu Leu Arg
260 265 270
Arg Arg Arg Arg Arg Arg Arg Arg
275 280
<210> 44
<211> 284
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 44
Met Ala Ala Thr His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys
1 5 10 15
Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met
20 25 30
His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala
35 40 45
Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly
50 55 60
Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp
65 70 75 80
Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys
85 90 95
Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala
100 105 110
Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr
115 120 125
Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Gly Lys
130 135 140
Leu Glu Val Ser Lys Ala Ala Thr Ile Lys Gln Ser Asp Val Lys Gln
145 150 155 160
Glu Val Lys Lys Gln Glu Ala Lys Gln Ile Val Lys Ala Thr Asp Trp
165 170 175
Lys Gln Asn Lys Asp Gly Ile Trp Tyr Lys Ala Glu His Ala Ser Phe
180 185 190
Thr Val Thr Ala Pro Glu Gly Ile Ile Thr Arg Tyr Lys Gly Pro Trp
195 200 205
Thr Gly His Pro Gln Ala Gly Val Leu Gln Lys Gly Gln Thr Ile Lys
210 215 220
Tyr Asp Glu Val Gln Lys Phe Asp Gly His Val Trp Val Ser Trp Glu
225 230 235 240
Thr Phe Glu Gly Glu Thr Val Tyr Met Pro Val Arg Thr Trp Asp Ala
245 250 255
Lys Thr Gly Lys Val Gly Lys Leu Trp Gly Glu Ile Lys Glu Leu Gly
260 265 270
Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Pro Gln
275 280
<210> 45
<211> 160
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 45
Met Ala Ala Thr His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys
1 5 10 15
Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met
20 25 30
His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala
35 40 45
Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly
50 55 60
Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp
65 70 75 80
Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys
85 90 95
Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala
100 105 110
Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr
115 120 125
Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Glu Leu
130 135 140
Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys
145 150 155 160
<210> 46
<211> 153
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 46
Met Ala Ala Thr His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys
1 5 10 15
Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met
20 25 30
His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala
35 40 45
Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly
50 55 60
Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp
65 70 75 80
Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys
85 90 95
Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala
100 105 110
Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr
115 120 125
Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Glu Leu
130 135 140
Arg Arg Arg Arg Arg Arg Arg Arg Arg
145 150
<210> 47
<211> 157
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽构建体
<400> 47
Met Ala Ala Thr His Glu His Ser Ala Gln Trp Leu Asn Asn Tyr Lys
1 5 10 15
Lys Gly Tyr Gly Tyr Gly Pro Tyr Pro Leu Gly Ile Asn Gly Gly Met
20 25 30
His Tyr Gly Val Asp Phe Phe Met Asn Ile Gly Thr Pro Val Lys Ala
35 40 45
Ile Ser Ser Gly Lys Ile Val Glu Ala Gly Trp Ser Asn Tyr Gly Gly
50 55 60
Gly Asn Gln Ile Gly Leu Ile Glu Asn Asp Gly Val His Arg Gln Trp
65 70 75 80
Tyr Met His Leu Ser Lys Tyr Asn Val Lys Val Gly Asp Tyr Val Lys
85 90 95
Ala Gly Gln Ile Ile Gly Trp Ser Gly Ser Thr Gly Tyr Ser Thr Ala
100 105 110
Pro His Leu His Phe Gln Arg Met Val Asn Ser Phe Ser Asn Ser Thr
115 120 125
Ala Gln Asp Pro Met Pro Phe Leu Lys Ser Ala Gly Tyr Gly Glu Leu
130 135 140
Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Pro Gln
145 150 155
<210> 48
<400> 48
000
<210> 49
<400> 49
000
<210> 50
<211> 981
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 50
atgctgaaac atatttactc caaccacatt aaaggtaaca aaatcacagc ccctaaaccg 60
tcaattcagg gcgtggtgat ccacaacgat tatggctcaa tgaccccttc acagtacctg 120
ccttggctgt acgctcgcga aaacaacggt acacatgtga atggctgggc ctcagtgtat 180
gccaatcgca acgaggtgct gtggtatcat cctacagact acgtggaatg gcactgcggc 240
aaccaatggg ccaacgccaa cctgatcggc tttgaagttt gcgaatcata tcctggtcgc 300
atctcagaca aactgtttct ggaaaacgag gaagccacac tgaaagtagc tgccgacgtg 360
atgaaatcgt atggcctgcc tgtgaatcgc aacacagtgc gcctgcacaa cgaatttttc 420
ggtacatcat gccctcatcg ttcatgggac ctgcacgtgg gcaaaggcga gccttatacc 480
acaacaaata tcaataaaat gaaagattat ttcattaaac ggattaaaca ctactatgac 540
ggtggcaaac tggaagttag caaagcagcc accattaaac agagtgatgt taaacaagaa 600
gtgaaaaaac aagaggccaa acaaattgtg aaagccaccg attggaaaca gaacaaagat 660
ggcatctggt ataaagcaga acatgccagc tttaccgtga ccgcaccgga aggcattatt 720
acccgttata aaggtccgtg gaccggtcat ccgcaggcag gcgtgctgca gaaaggtcag 780
accatcaaat atgatgaagt gcagaaattt gatggccatg tttgggttag ctgggaaacc 840
tttgaaggtg aaaccgttta tatgccggtt cgtacctggg atgcaaaaac cggtaaagtt 900
ggtaaactgt ggggtgagat taaagagctc cgccagatca aaatttggtt tcagaatcgt 960
cgcatgaaat ggaaaaaata a 981
<210> 51
<211> 960
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 51
atgctgaaac atatttactc caaccacatt aaaggtaaca aaatcacagc ccctaaaccg 60
tcaattcagg gcgtggtgat ccacaacgat tatggctcaa tgaccccttc acagtacctg 120
ccttggctgt acgctcgcga aaacaacggt acacatgtga atggctgggc ctcagtgtat 180
gccaatcgca acgaggtgct gtggtatcat cctacagact acgtggaatg gcactgcggc 240
aaccaatggg ccaacgccaa cctgatcggc tttgaagttt gcgaatcata tcctggtcgc 300
atctcagaca aactgtttct ggaaaacgag gaagccacac tgaaagtagc tgccgacgtg 360
atgaaatcgt atggcctgcc tgtgaatcgc aacacagtgc gcctgcacaa cgaatttttc 420
ggtacatcat gccctcatcg ttcatgggac ctgcacgtgg gcaaaggcga gccttatacc 480
acaacaaata tcaataaaat gaaagattat ttcattaaac ggattaaaca ctactatgac 540
ggtggcaaac tggaagttag caaagcagcc accattaaac agagtgatgt taaacaagaa 600
gtgaaaaaac aagaggccaa acaaattgtg aaagccaccg attggaaaca gaacaaagat 660
ggcatctggt ataaagcaga acatgccagc tttaccgtga ccgcaccgga aggcattatt 720
acccgttata aaggtccgtg gaccggtcat ccgcaggcag gcgtgctgca gaaaggtcag 780
accatcaaat atgatgaagt gcagaaattt gatggccatg tttgggttag ctgggaaacc 840
tttgaaggtg aaaccgttta tatgccggtt cgtacctggg atgcaaaaac cggtaaagtt 900
ggtaaactgt ggggtgagat taaagagctc cgtcgtcgtc gccgtcggcg tcgtcgttaa 960
<210> 52
<211> 972
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 52
atgctgaaac atatttactc caaccacatt aaaggtaaca aaatcacagc ccctaaaccg 60
tcaattcagg gcgtggtgat ccacaacgat tatggctcaa tgaccccttc acagtacctg 120
ccttggctgt acgctcgcga aaacaacggt acacatgtga atggctgggc ctcagtgtat 180
gccaatcgca acgaggtgct gtggtatcat cctacagact acgtggaatg gcactgcggc 240
aaccaatggg ccaacgccaa cctgatcggc tttgaagttt gcgaatcata tcctggtcgc 300
atctcagaca aactgtttct ggaaaacgag gaagccacac tgaaagtagc tgccgacgtg 360
atgaaatcgt atggcctgcc tgtgaatcgc aacacagtgc gcctgcacaa cgaatttttc 420
ggtacatcat gccctcatcg ttcatgggac ctgcacgtgg gcaaaggcga gccttatacc 480
acaacaaata tcaataaaat gaaagattat ttcattaaac ggattaaaca ctactatgac 540
ggtggcaaac tggaagttag caaagcagcc accattaaac agagtgatgt taaacaagaa 600
gtgaaaaaac aagaggccaa acaaattgtg aaagccaccg attggaaaca gaacaaagat 660
ggcatctggt ataaagcaga acatgccagc tttaccgtga ccgcaccgga aggcattatt 720
acccgttata aaggtccgtg gaccggtcat ccgcaggcag gcgtgctgca gaaaggtcag 780
accatcaaat atgatgaagt gcagaaattt gatggccatg tttgggttag ctgggaaacc 840
tttgaaggtg aaaccgttta tatgccggtt cgtacctggg atgcaaaaac cggtaaagtt 900
ggtaaactgt ggggtgagat taaagagctc ggtcgtaaaa aacgtcgtca gcgtcgtcgt 960
ccgcctcagt aa 972
<210> 53
<211> 600
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 53
atgctgaaac atatttactc caaccacatt aaaggtaaca aaatcacagc ccctaaaccg 60
tcaattcagg gcgtggtgat ccacaacgat tatggctcaa tgaccccttc acagtacctg 120
ccttggctgt acgctcgcga aaacaacggt acacatgtga atggctgggc ctcagtgtat 180
gccaatcgca acgaggtgct gtggtatcat cctacagact acgtggaatg gcactgcggc 240
aaccaatggg ccaacgccaa cctgatcggc tttgaagttt gcgaatcata tcctggtcgc 300
atctcagaca aactgtttct ggaaaacgag gaagccacac tgaaagtagc tgccgacgtg 360
atgaaatcgt atggcctgcc tgtgaatcgc aacacagtgc gcctgcacaa cgaatttttc 420
ggtacatcat gccctcatcg ttcatgggac ctgcacgtgg gcaaaggcga gccttatacc 480
acaacaaata tcaataaaat gaaagattat ttcattaaac ggattaaaca ctactatgac 540
ggtgagctcc gccagatcaa aatttggttt cagaatcgtc gcatgaaatg gaaaaaataa 600
<210> 54
<211> 579
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 54
atgctgaaac atatttactc caaccacatt aaaggtaaca aaatcacagc ccctaaaccg 60
tcaattcagg gcgtggtgat ccacaacgat tatggctcaa tgaccccttc acagtacctg 120
ccttggctgt acgctcgcga aaacaacggt acacatgtga atggctgggc ctcagtgtat 180
gccaatcgca acgaggtgct gtggtatcat cctacagact acgtggaatg gcactgcggc 240
aaccaatggg ccaacgccaa cctgatcggc tttgaagttt gcgaatcata tcctggtcgc 300
atctcagaca aactgtttct ggaaaacgag gaagccacac tgaaagtagc tgccgacgtg 360
atgaaatcgt atggcctgcc tgtgaatcgc aacacagtgc gcctgcacaa cgaatttttc 420
ggtacatcat gccctcatcg ttcatgggac ctgcacgtgg gcaaaggcga gccttatacc 480
acaacaaata tcaataaaat gaaagattat ttcattaaac ggattaaaca ctactatgac 540
ggtgagctcc gtcgtcgtcg ccgtcggcgt cgtcgttaa 579
<210> 55
<211> 591
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 55
atgctgaaac atatttactc caaccacatt aaaggtaaca aaatcacagc ccctaaaccg 60
tcaattcagg gcgtggtgat ccacaacgat tatggctcaa tgaccccttc acagtacctg 120
ccttggctgt acgctcgcga aaacaacggt acacatgtga atggctgggc ctcagtgtat 180
gccaatcgca acgaggtgct gtggtatcat cctacagact acgtggaatg gcactgcggc 240
aaccaatggg ccaacgccaa cctgatcggc tttgaagttt gcgaatcata tcctggtcgc 300
atctcagaca aactgtttct ggaaaacgag gaagccacac tgaaagtagc tgccgacgtg 360
atgaaatcgt atggcctgcc tgtgaatcgc aacacagtgc gcctgcacaa cgaatttttc 420
ggtacatcat gccctcatcg ttcatgggac ctgcacgtgg gcaaaggcga gccttatacc 480
acaacaaata tcaataaaat gaaagattat ttcattaaac ggattaaaca ctactatgac 540
ggtgagctcg gtcgtaaaaa acgtcgtcag cgtcgtcgtc cgcctcagta a 591
<210> 56
<211> 924
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 56
atgtccatta tcatggaagt ggccacaatg caagccaaac tgacaaaaaa tgagttcatt 60
gagtggctga aaacgtccga gggtaaacag ttcaacgtgg acctgtggta cggttttcag 120
tgtttcgact acgccaacgc tggctggaaa gtgctgttcg gcctgctgct gaaaggcctg 180
ggagccaaag acatcccttt tgcaaacaat ttcgatggcc tggccacagt ttatcaaaac 240
acccctgact ttctggccca accaggcgac atggtggtgt ttggttctaa ttatggcgca 300
ggctatggcc acgtagcctg ggtgatcgaa gccacactgg actacattat tgtttatgag 360
caaaactggc tgggaggcgg atggacagac ggcatcgaac agcctggctg gggctgggag 420
aaagtgacac gccgtcaaca tgcctatgac ttccctatgt ggttcatccg tcctaatttc 480
aaaggtggta aactggaagt tagcaaagca gcaaccatta aacagtccga tgttaaacaa 540
gaagtgaaaa aacaagaggc caaacaaatt gtgaaagcca ccgattggaa acagaacaaa 600
gatggcattt ggtataaagc agaacatgcc agctttaccg ttaccgcacc ggaaggcatt 660
attacccgtt ataaaggtcc gtggaccggt catccgcagg caggcgtact gcagaaaggt 720
cagaccatta aatacgatga agtgcagaaa tttgatggcc atgtttgggt tagctgggaa 780
acctttgaag gtgaaaccgt ttatatgccg gttcgtacct gggatgcaaa aaccggtaaa 840
gtgggcaaac tgtggggtga aatcaaagag ctccgccaga tcaaaatttg gtttcagaat 900
cgtcgcatga aatggaaaaa ataa 924
<210> 57
<211> 903
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 57
atgtccatta tcatggaagt ggccacaatg caagccaaac tgacaaaaaa tgagttcatt 60
gagtggctga aaacgtccga gggtaaacag ttcaacgtgg acctgtggta cggttttcag 120
tgtttcgact acgccaacgc tggctggaaa gtgctgttcg gcctgctgct gaaaggcctg 180
ggagccaaag acatcccttt tgcaaacaat ttcgatggcc tggccacagt ttatcaaaac 240
acccctgact ttctggccca accaggcgac atggtggtgt ttggttctaa ttatggcgca 300
ggctatggcc acgtagcctg ggtgatcgaa gccacactgg actacattat tgtttatgag 360
caaaactggc tgggaggcgg atggacagac ggcatcgaac agcctggctg gggctgggag 420
aaagtgacac gccgtcaaca tgcctatgac ttccctatgt ggttcatccg tcctaatttc 480
aaaggtggta aactggaagt tagcaaagca gcaaccatta aacagtccga tgttaaacaa 540
gaagtgaaaa aacaagaggc caaacaaatt gtgaaagcca ccgattggaa acagaacaaa 600
gatggcattt ggtataaagc agaacatgcc agctttaccg ttaccgcacc ggaaggcatt 660
attacccgtt ataaaggtcc gtggaccggt catccgcagg caggcgtact gcagaaaggt 720
cagaccatta aatacgatga agtgcagaaa tttgatggcc atgtttgggt tagctgggaa 780
acctttgaag gtgaaaccgt ttatatgccg gttcgtacct gggatgcaaa aaccggtaaa 840
gtgggcaaac tgtggggtga aatcaaagag ctccgtcgtc gtcgccgtcg gcgtcgtcgt 900
taa 903
<210> 58
<211> 915
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 58
atgtccatta tcatggaagt ggccacaatg caagccaaac tgacaaaaaa tgagttcatt 60
gagtggctga aaacgtccga gggtaaacag ttcaacgtgg acctgtggta cggttttcag 120
tgtttcgact acgccaacgc tggctggaaa gtgctgttcg gcctgctgct gaaaggcctg 180
ggagccaaag acatcccttt tgcaaacaat ttcgatggcc tggccacagt ttatcaaaac 240
acccctgact ttctggccca accaggcgac atggtggtgt ttggttctaa ttatggcgca 300
ggctatggcc acgtagcctg ggtgatcgaa gccacactgg actacattat tgtttatgag 360
caaaactggc tgggaggcgg atggacagac ggcatcgaac agcctggctg gggctgggag 420
aaagtgacac gccgtcaaca tgcctatgac ttccctatgt ggttcatccg tcctaatttc 480
aaaggtggta aactggaagt tagcaaagca gcaaccatta aacagtccga tgttaaacaa 540
gaagtgaaaa aacaagaggc caaacaaatt gtgaaagcca ccgattggaa acagaacaaa 600
gatggcattt ggtataaagc agaacatgcc agctttaccg ttaccgcacc ggaaggcatt 660
attacccgtt ataaaggtcc gtggaccggt catccgcagg caggcgtact gcagaaaggt 720
cagaccatta aatacgatga agtgcagaaa tttgatggcc atgtttgggt tagctgggaa 780
acctttgaag gtgaaaccgt ttatatgccg gttcgtacct gggatgcaaa aaccggtaaa 840
gtgggcaaac tgtggggtga aatcaaagag ctcggtcgta aaaaacgtcg tcagcgtcgt 900
cgtccgcctc agtaa 915
<210> 59
<211> 540
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 59
atgtccatta tcatggaagt ggccacaatg caagccaaac tgacaaaaaa tgagttcatt 60
gagtggctga aaacgtccga gggtaaacag ttcaacgtgg acctgtggta cggttttcag 120
tgtttcgact acgccaacgc tggctggaaa gtgctgttcg gcctgctgct gaaaggcctg 180
ggagccaaag acatcccttt tgcaaacaat ttcgatggcc tggccacagt ttatcaaaac 240
acccctgact ttctggccca accaggcgac atggtggtgt ttggttctaa ttatggcgca 300
ggctatggcc acgtagcctg ggtgatcgaa gccacactgg actacattat tgtttatgag 360
caaaactggc tgggaggcgg atggacagac ggcatcgaac agcctggctg gggctgggag 420
aaagtgacac gccgtcaaca tgcctatgac ttccctatgt ggttcatccg tcctaatttc 480
aaagagctcc gccagatcaa aatttggttt cagaatcgtc gcatgaaatg gaaaaaataa 540
<210> 60
<211> 519
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 60
atgtccatta tcatggaagt ggccacaatg caagccaaac tgacaaaaaa tgagttcatt 60
gagtggctga aaacgtccga gggtaaacag ttcaacgtgg acctgtggta cggttttcag 120
tgtttcgact acgccaacgc tggctggaaa gtgctgttcg gcctgctgct gaaaggcctg 180
ggagccaaag acatcccttt tgcaaacaat ttcgatggcc tggccacagt ttatcaaaac 240
acccctgact ttctggccca accaggcgac atggtggtgt ttggttctaa ttatggcgca 300
ggctatggcc acgtagcctg ggtgatcgaa gccacactgg actacattat tgtttatgag 360
caaaactggc tgggaggcgg atggacagac ggcatcgaac agcctggctg gggctgggag 420
aaagtgacac gccgtcaaca tgcctatgac ttccctatgt ggttcatccg tcctaatttc 480
aaagagctcc gtcgtcgtcg ccgtcggcgt cgtcgttaa 519
<210> 61
<211> 531
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 61
atgtccatta tcatggaagt ggccacaatg caagccaaac tgacaaaaaa tgagttcatt 60
gagtggctga aaacgtccga gggtaaacag ttcaacgtgg acctgtggta cggttttcag 120
tgtttcgact acgccaacgc tggctggaaa gtgctgttcg gcctgctgct gaaaggcctg 180
ggagccaaag acatcccttt tgcaaacaat ttcgatggcc tggccacagt ttatcaaaac 240
acccctgact ttctggccca accaggcgac atggtggtgt ttggttctaa ttatggcgca 300
ggctatggcc acgtagcctg ggtgatcgaa gccacactgg actacattat tgtttatgag 360
caaaactggc tgggaggcgg atggacagac ggcatcgaac agcctggctg gggctgggag 420
aaagtgacac gccgtcaaca tgcctatgac ttccctatgt ggttcatccg tcctaatttc 480
aaagagctcg gtcgtaaaaa acgtcgtcag cgtcgtcgtc cgcctcagta a 531
<210> 62
<211> 864
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 62
atggcagcca cacatgaaca ctctgcccaa tggctgaaca actacaaaaa aggctacggt 60
tatggccctt accctctggg cattaacggt ggcatgcact acggcgttga cttttttatg 120
aacatcggca cccctgtgaa agccattagc tcaggcaaaa tcgtggaagc cggttggtca 180
aactatggcg gtggcaacca gatcggtctg atcgagaacg atggtgtgca ccgccaatgg 240
tacatgcacc tgtccaaata caacgttaaa gttggtgact acgtgaaagc aggccagatt 300
atcggctggt caggttcaac cggttattca acagcccctc atctgcactt ccaacgcatg 360
gtgaatagtt ttagtaattc taccgctcaa gatccgatgc cattcctgaa atctgccggt 420
tatggtggca aactggaagt tagcaaagca gcaaccatta aacagtccga tgttaaacaa 480
gaagtgaaaa aacaagaggc caaacaaatt gtgaaagcga ccgattggaa acagaacaaa 540
gatggcattt ggtataaagc agaacatgcc agctttaccg tgaccgcacc ggaaggcatt 600
attacccgtt ataaaggtcc gtggaccggt catccgcagg caggcgtgct gcagaaaggt 660
cagaccatca aatatgatga ggtgcagaaa tttgatggcc atgtttgggt tagctgggaa 720
acctttgaag gtgaaaccgt ttatatgccg gttcgtacct gggatgcaaa aaccggtaaa 780
gtgggtaaac tgtggggtga aatcaaagag ctccgccaga tcaaaatttg gtttcagaat 840
cgtcgcatga aatggaaaaa ataa 864
<210> 63
<211> 843
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 63
atggcagcca cacatgaaca ctctgcccaa tggctgaaca actacaaaaa aggctacggt 60
tatggccctt accctctggg cattaacggt ggcatgcact acggcgttga cttttttatg 120
aacatcggca cccctgtgaa agccattagc tcaggcaaaa tcgtggaagc cggttggtca 180
aactatggcg gtggcaacca gatcggtctg atcgagaacg atggtgtgca ccgccaatgg 240
tacatgcacc tgtccaaata caacgttaaa gttggtgact acgtgaaagc aggccagatt 300
atcggctggt caggttcaac cggttattca acagcccctc atctgcactt ccaacgcatg 360
gtgaatagtt ttagtaattc taccgctcaa gatccgatgc cattcctgaa atctgccggt 420
tatggtggca aactggaagt tagcaaagca gcaaccatta aacagtccga tgttaaacaa 480
gaagtgaaaa aacaagaggc caaacaaatt gtgaaagcga ccgattggaa acagaacaaa 540
gatggcattt ggtataaagc agaacatgcc agctttaccg tgaccgcacc ggaaggcatt 600
attacccgtt ataaaggtcc gtggaccggt catccgcagg caggcgtgct gcagaaaggt 660
cagaccatca aatatgatga ggtgcagaaa tttgatggcc atgtttgggt tagctgggaa 720
acctttgaag gtgaaaccgt ttatatgccg gttcgtacct gggatgcaaa aaccggtaaa 780
gtgggtaaac tgtggggtga aatcaaagag ctccgtcgtc gtcgccgtcg gcgtcgtcgt 840
taa 843
<210> 64
<211> 855
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 64
atggcagcca cacatgaaca ctctgcccaa tggctgaaca actacaaaaa aggctacggt 60
tatggccctt accctctggg cattaacggt ggcatgcact acggcgttga cttttttatg 120
aacatcggca cccctgtgaa agccattagc tcaggcaaaa tcgtggaagc cggttggtca 180
aactatggcg gtggcaacca gatcggtctg atcgagaacg atggtgtgca ccgccaatgg 240
tacatgcacc tgtccaaata caacgttaaa gttggtgact acgtgaaagc aggccagatt 300
atcggctggt caggttcaac cggttattca acagcccctc atctgcactt ccaacgcatg 360
gtgaatagtt ttagtaattc taccgctcaa gatccgatgc cattcctgaa atctgccggt 420
tatggtggca aactggaagt tagcaaagca gcaaccatta aacagtccga tgttaaacaa 480
gaagtgaaaa aacaagaggc caaacaaatt gtgaaagcga ccgattggaa acagaacaaa 540
gatggcattt ggtataaagc agaacatgcc agctttaccg tgaccgcacc ggaaggcatt 600
attacccgtt ataaaggtcc gtggaccggt catccgcagg caggcgtgct gcagaaaggt 660
cagaccatca aatatgatga ggtgcagaaa tttgatggcc atgtttgggt tagctgggaa 720
acctttgaag gtgaaaccgt ttatatgccg gttcgtacct gggatgcaaa aaccggtaaa 780
gtgggtaaac tgtggggtga aatcaaagag ctcggtcgta aaaaacgtcg tcagcgtcgt 840
cgtccgcctc agtaa 855
<210> 65
<211> 483
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 65
atggcagcca cacatgaaca ctctgcccaa tggctgaaca actacaaaaa aggctacggt 60
tatggccctt accctctggg cattaacggt ggcatgcact acggcgttga cttttttatg 120
aacatcggca cccctgtgaa agccattagc tcaggcaaaa tcgtggaagc cggttggtca 180
aactatggcg gtggcaacca gatcggtctg atcgagaacg atggtgtgca ccgccaatgg 240
tacatgcacc tgtccaaata caacgttaaa gttggtgact acgtgaaagc aggccagatt 300
atcggctggt caggttcaac cggttattca acagcccctc atctgcactt ccaacgcatg 360
gtgaatagtt ttagtaattc taccgctcaa gatccgatgc cattcctgaa atctgccggt 420
tatggtgagc tccgccagat caaaatttgg tttcagaatc gtcgcatgaa atggaaaaaa 480
taa 483
<210> 66
<211> 462
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 66
atggcagcca cacatgaaca ctctgcccaa tggctgaaca actacaaaaa aggctacggt 60
tatggccctt accctctggg cattaacggt ggcatgcact acggcgttga cttttttatg 120
aacatcggca cccctgtgaa agccattagc tcaggcaaaa tcgtggaagc cggttggtca 180
aactatggcg gtggcaacca gatcggtctg atcgagaacg atggtgtgca ccgccaatgg 240
tacatgcacc tgtccaaata caacgttaaa gttggtgact acgtgaaagc aggccagatt 300
atcggctggt caggttcaac cggttattca acagcccctc atctgcactt ccaacgcatg 360
gtgaatagtt ttagtaattc taccgctcaa gatccgatgc cattcctgaa atctgccggt 420
tatggtgagc tccgtcgtcg tcgccgtcgg cgtcgtcgtt aa 462
<210> 67
<211> 474
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 多核苷酸
<400> 67
atggcagcca cacatgaaca ctctgcccaa tggctgaaca actacaaaaa aggctacggt 60
tatggccctt accctctggg cattaacggt ggcatgcact acggcgttga cttttttatg 120
aacatcggca cccctgtgaa agccattagc tcaggcaaaa tcgtggaagc cggttggtca 180
aactatggcg gtggcaacca gatcggtctg atcgagaacg atggtgtgca ccgccaatgg 240
tacatgcacc tgtccaaata caacgttaaa gttggtgact acgtgaaagc aggccagatt 300
atcggctggt caggttcaac cggttattca acagcccctc atctgcactt ccaacgcatg 360
gtgaatagtt ttagtaattc taccgctcaa gatccgatgc cattcctgaa atctgccggt 420
tatggtgagc tcggtcgtaa aaaacgtcgt cagcgtcgtc gtccgcctca gtaa 474
<210> 68
<400> 68
000
<210> 69
<400> 69
000
<210> 70
<211> 37
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 70
Leu Leu Gly Asp Phe Phe Arg Lys Ser Lys Glu Lys Ile Gly Lys Glu
1 5 10 15
Phe Lys Arg Ile Val Gln Arg Ile Lys Asp Phe Leu Arg Asn Leu Val
20 25 30
Pro Arg Thr Glu Ser
35
<210> 71
<211> 29
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 71
Arg Gly Leu Arg Arg Leu Gly Arg Lys Ile Ala His Gly Val Lys Lys
1 5 10 15
Tyr Gly Pro Thr Val Leu Arg Ile Ile Arg Ile Ala Gly
20 25
<210> 72
<211> 13
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 72
Ile Leu Pro Trp Lys Trp Pro Trp Trp Pro Trp Arg Arg
1 5 10
<210> 73
<211> 18
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 73
Arg Gly Gly Arg Leu Cys Tyr Cys Arg Arg Arg Phe Cys Val Cys Val
1 5 10 15
Gly Arg
<210> 74
<211> 31
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 74
Ser Trp Leu Ser Lys Thr Ala Lys Lys Leu Glu Asn Ser Ala Lys Lys
1 5 10 15
Arg Ile Ser Glu Gly Ile Ala Ile Ala Ile Gln Gly Gly Pro Arg
20 25 30
<210> 75
<211> 23
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 75
Gly Ile Gly Lys Phe Leu His Ser Ala Lys Lys Phe Gly Lys Ala Phe
1 5 10 15
Val Gly Glu Ile Met Asn Ser
20
<210> 76
<211> 25
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 76
Gly Trp Gly Ser Phe Phe Lys Lys Ala Ala His Val Gly Lys His Val
1 5 10 15
Gly Lys Ala Ala Leu Thr His Tyr Leu
20 25
<210> 77
<211> 36
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 77
Gly Gly Leu Lys Lys Leu Gly Lys Lys Leu Glu Gly Ala Gly Lys Arg
1 5 10 15
Val Phe Asn Ala Ala Glu Lys Ala Leu Pro Val Val Ala Gly Ala Lys
20 25 30
Ala Leu Arg Lys
35
<210> 78
<211> 40
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 78
Gly Trp Leu Lys Lys Ile Gly Lys Lys Ile Glu Arg Val Gly Gln His
1 5 10 15
Thr Arg Asp Ala Thr Ile Gln Gly Leu Gly Ile Pro Gln Gln Ala Ala
20 25 30
Asn Val Ala Ala Thr Ala Arg Gly
35 40
<210> 79
<211> 21
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 79
Thr Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro Val Gly Arg Val His
1 5 10 15
Arg Leu Leu Arg Lys
20
<210> 80
<211> 39
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 80
Gly Trp Leu Lys Lys Ile Gly Lys Lys Ile Glu Arg Val Gly Gln His
1 5 10 15
Thr Arg Asp Ala Thr Ile Gln Gly Leu Gly Ile Ala Gln Gln Ala Ala
20 25 30
Asn Val Ala Ala Thr Ala Arg
35
<210> 81
<211> 24
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 81
Gly Ile Lys Asp Trp Ile Lys Gly Ala Ala Lys Lys Leu Ile Lys Thr
1 5 10 15
Val Ala Ser His Ile Ala Asn Gln
20
<210> 82
<211> 17
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 82
Ala Asn Arg Pro Val Tyr Ile Pro Pro Pro Arg Pro Pro His Pro Arg
1 5 10 15
Leu
<210> 83
<211> 22
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 83
Gly Leu Leu Ser Lys Val Leu Gly Val Gly Lys Lys Val Leu Cys Gly
1 5 10 15
Val Ser Gly Leu Val Cys
20
<210> 84
<211> 24
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 84
Gly Leu Asn Thr Leu Lys Lys Val Phe Gln Gly Leu His Glu Ala Ile
1 5 10 15
Lys Leu Ile Asn Asn His Val Gln
20
<210> 85
<211> 19
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 85
Lys Gly Arg Gly Lys Gln Gly Gly Lys Val Arg Ala Lys Ala Lys Thr
1 5 10 15
Arg Ser Ser
<210> 86
<211> 25
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 86
Ile Trp Leu Thr Ala Leu Lys Phe Leu Gly Lys His Ala Ala Lys Lys
1 5 10 15
Leu Ala Lys Gln Gln Leu Ser Lys Leu
20 25
<210> 87
<211> 18
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 87
Phe Leu Gly Gly Leu Ile Val Pro Ala Met Ile Cys Ala Val Thr Lys
1 5 10 15
Lys Cys
<210> 88
<211> 26
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 88
Gly Ile Gly Ala Val Leu Lys Val Leu Thr Thr Gly Leu Pro Ala Leu
1 5 10 15
Ile Ser Trp Ile Lys Arg Lys Arg Gln Gln
20 25
<210> 89
<211> 54
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 89
Lys Thr Tyr Tyr Gly Thr Asn Gly Val His Cys Thr Lys Asn Ser Leu
1 5 10 15
Trp Gly Lys Val Arg Leu Lys Asn Met Lys Tyr Asp Gln Asn Thr Thr
20 25 30
Tyr Met Gly Arg Leu Gln Asp Ile Leu Leu Gly Trp Ala Thr Gly Ala
35 40 45
Phe Gly Lys Thr Phe His
50
<210> 90
<211> 39
<212> PRT
<213> 人工的（Artificial）
<220>
<221> DOMAIN
<223> 多肽片段
<400> 90
Ala Gly Arg Gly Lys Gln Gly Gly Lys Val Arg Ala Lys Ala Lys Thr
1 5 10 15
Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro Val Gly Arg Val His Arg
20 25 30
Leu Leu Arg Lys Gly Asn Tyr
35
<210> 91
<211> 6628
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 91
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gctgaaacat 120
atttactcca accacattaa aggtaacaaa atcacagccc ctaaaccgtc aattcagggc 180
gtggtgatcc acaacgatta tggctcaatg accccttcac agtacctgcc ttggctgtac 240
gctcgcgaaa acaacggtac acatgtgaat ggctgggcct cagtgtatgc caatcgcaac 300
gaggtgctgt ggtatcatcc tacagactac gtggaatggc actgcggcaa ccaatgggcc 360
aacgccaacc tgatcggctt tgaagtttgc gaatcatatc ctggtcgcat ctcagacaaa 420
ctgtttctgg aaaacgagga agccacactg aaagtagctg ccgacgtgat gaaatcgtat 480
ggcctgcctg tgaatcgcaa cacagtgcgc ctgcacaacg aatttttcgg tacatcatgc 540
cctcatcgtt catgggacct gcacgtgggc aaaggcgagc cttataccac aacaaatatc 600
aataaaatga aagattattt cattaaacgg attaaacact actatgacgg tggcaaactg 660
gaagttagca aagcagccac cattaaacag agtgatgtta aacaagaagt gaaaaaacaa 720
gaggccaaac aaattgtgaa agccaccgat tggaaacaga acaaagatgg catctggtat 780
aaagcagaac atgccagctt taccgtgacc gcaccggaag gcattattac ccgttataaa 840
ggtccgtgga ccggtcatcc gcaggcaggc gtgctgcaga aaggtcagac catcaaatat 900
gatgaagtgc agaaatttga tggccatgtt tgggttagct gggaaacctt tgaaggtgaa 960
accgtttata tgccggttcg tacctgggat gcaaaaaccg gtaaagttgg taaactgtgg 1020
ggtgagatta aagagctccg ccagatcaaa atttggtttc agaatcgtcg catgaaatgg 1080
aaaaaataag gatccggctg ctaacaaagc ccgaaaggaa gctgagttgg ctgctgccac 1140
cgctgagcaa taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt 1200
gctgaaagga ggaactatat ccggatatcc cgcaagaggc ccggcagtac cggcataacc 1260
aagcctatgc ctacagcatc cagggtgacg gtgccgagga tgacgatgag cgcattgtta 1320
gatttcatac acggtgcctg actgcgttag caatttaact gtgataaact accgcattaa 1380
agctagctta tcgatgataa gctgtcaaac atgagaatta attcttgaag acgaaagggc 1440
ctcgtgatac gcctattttt ataggttaat gtcatgataa taatggtttc ttagacgtca 1500
ggtggcactt ttcggggaaa tgtgcgcgga acccctattt gtttattttt ctaaatacat 1560
tcaaatatgt atccgctcat gagacaataa ccctgataaa tgcttcaata atattgaaaa 1620
aggaagagta tgagtattca acatttccgt gtcgccctta ttcccttttt tgcggcattt 1680
tgccttcctg tttttgctca cccagaaacg ctggtgaaag taaaagatgc tgaagatcag 1740
ttgggtgcac gagtgggtta catcgaactg gatctcaaca gcggtaagat ccttgagagt 1800
tttcgccccg aagaacgttt tccaatgatg agcactttta aagttctgct atgtggcgcg 1860
gtattatccc gtgttgacgc cgggcaagag caactcggtc gccgcataca ctattctcag 1920
aatgacttgg ttgagtactc accagtcaca gaaaagcatc ttacggatgg catgacagta 1980
agagaattat gcagtgctgc cataaccatg agtgataaca ctgcggccaa cttacttctg 2040
acaacgatcg gaggaccgaa ggagctaacc gcttttttgc acaacatggg ggatcatgta 2100
actcgccttg atcgttggga accggagctg aatgaagcca taccaaacga cgagcgtgac 2160
accacgatgc ctgcagcaat ggcaacaacg ttgcgcaaac tattaactgg cgaactactt 2220
actctagctt cccggcaaca attaatagac tggatggagg cggataaagt tgcaggacca 2280
cttctgcgct cggcccttcc ggctggctgg tttattgctg ataaatctgg agccggtgag 2340
cgtgggtctc gcggtatcat tgcagcactg gggccagatg gtaagccctc ccgtatcgta 2400
gttatctaca cgacggggag tcaggcaact atggatgaac gaaatagaca gatcgctgag 2460
ataggtgcct cactgattaa gcattggtaa ctgtcagacc aagtttactc atatatactt 2520
tagattgatt taaaacttca tttttaattt aaaaggatct aggtgaagat cctttttgat 2580
aatctcatga ccaaaatccc ttaacgtgag ttttcgttcc actgagcgtc agaccccgta 2640
gaaaagatca aaggatcttc ttgagatcct ttttttctgc gcgtaatctg ctgcttgcaa 2700
acaaaaaaac caccgctacc agcggtggtt tgtttgccgg atcaagagct accaactctt 2760
tttccgaagg taactggctt cagcagagcg cagataccaa atactgtcct tctagtgtag 2820
ccgtagttag gccaccactt caagaactct gtagcaccgc ctacatacct cgctctgcta 2880
atcctgttac cagtggctgc tgccagtggc gataagtcgt gtcttaccgg gttggactca 2940
agacgatagt taccggataa ggcgcagcgg tcgggctgaa cggggggttc gtgcacacag 3000
cccagcttgg agcgaacgac ctacaccgaa ctgagatacc tacagcgtga gctatgagaa 3060
agcgccacgc ttcccgaagg gagaaaggcg gacaggtatc cggtaagcgg cagggtcgga 3120
acaggagagc gcacgaggga gcttccaggg ggaaacgcct ggtatcttta tagtcctgtc 3180
gggtttcgcc acctctgact tgagcgtcga tttttgtgat gctcgtcagg ggggcggagc 3240
ctatggaaaa acgccagcaa cgcggccttt ttacggttcc tggccttttg ctggcctttt 3300
gctcacatgt tctttcctgc gttatcccct gattctgtgg ataaccgtat taccgccttt 3360
gagtgagctg ataccgctcg ccgcagccga acgaccgagc gcagcgagtc agtgagcgag 3420
gaagcggaag agcgcctgat gcggtatttt ctccttacgc atctgtgcgg tatttcacac 3480
cgcaatggtg cactctcagt acaatctgct ctgatgccgc atagttaagc cagtatacac 3540
tccgctatcg ctacgtgact gggtcatggc tgcgccccga cacccgccaa cacccgctga 3600
cgcgccctga cgggcttgtc tgctcccggc atccgcttac agacaagctg tgaccgtctc 3660
cgggagctgc atgtgtcaga ggttttcacc gtcatcaccg aaacgcgcga ggcagctgcg 3720
gtaaagctca tcagcgtggt cgtgaagcga ttcacagatg tctgcctgtt catccgcgtc 3780
cagctcgttg agtttctcca gaagcgttaa tgtctggctt ctgataaagc gggccatgtt 3840
aagggcggtt ttttcctgtt tggtcactga tgcctccgtg taagggggat ttctgttcat 3900
gggggtaatg ataccgatga aacgagagag gatgctcacg atacgggtta ctgatgatga 3960
acatgcccgg ttactggaac gttgtgaggg taaacaactg gcggtatgga tgcggcggga 4020
ccagagaaaa atcactcagg gtcaatgcca gcgcttcgtt aatacagatg taggtgttcc 4080
acagggtagc cagcagcatc ctgcgatgca gatccggaac ataatggtgc agggcgctga 4140
cttccgcgtt tccagacttt acgaaacacg gaaaccgaag accattcatg ttgttgctca 4200
ggtcgcagac gttttgcagc agcagtcgct tcacgttcgc tcgcgtatcg gtgattcatt 4260
ctgctaacca gtaaggcaac cccgccagcc tagccgggtc ctcaacgaca ggagcacgat 4320
catgcgcacc cgtggccagg acccaacgct gcccgagatg cgccgcgtgc ggctgctgga 4380
gatggcggac gcgatggata tgttctgcca agggttggtt tgcgcattca cagttctccg 4440
caagaattga ttggctccaa ttcttggagt ggtgaatccg ttagcgaggt gccgccggct 4500
tccattcagg tcgaggtggc ccggctccat gcaccgcgac gcaacgcggg gaggcagaca 4560
aggtataggg cggcgcctac aatccatgcc aacccgttcc atgtgctcgc cgaggcggca 4620
taaatcgccg tgacgatcag cggtccaatg atcgaagtta ggctggtaag agccgcgagc 4680
gatccttgaa gctgtccctg atggtcgtca tctacctgcc tggacagcat ggcctgcaac 4740
gcgggcatcc cgatgccgcc ggaagcgaga agaatcataa tggggaaggc catccagcct 4800
cgcgtcgcga acgccagcaa gacgtagccc agcgcgtcgg ccgccatgcc ggcgataatg 4860
gcctgcttct cgccgaaacg tttggtggcg ggaccagtga cgaaggcttg agcgagggcg 4920
tgcaagattc cgaataccgc aagcgacagg ccgatcatcg tcgcgctcca gcgaaagcgg 4980
tcctcgccga aaatgaccca gagcgctgcc ggcacctgtc ctacgagttg catgataaag 5040
aagacagtca taagtgcggc gacgatagtc atgccccgcg cccaccggaa ggagctgact 5100
gggttgaagg ctctcaaggg catcggtcga gatcccggtg cctaatgagt gagctaactt 5160
acattaattg cgttgcgctc actgcccgct ttccagtcgg gaaacctgtc gtgccagctg 5220
cattaatgaa tcggccaacg cgcggggaga ggcggtttgc gtattgggcg ccagggtggt 5280
ttttcttttc accagtgaga cgggcaacag ctgattgccc ttcaccgcct ggccctgaga 5340
gagttgcagc aagcggtcca cgctggtttg ccccagcagg cgaaaatcct gtttgatggt 5400
ggttaacggc gggatataac atgagctgtc ttcggtatcg tcgtatccca ctaccgagat 5460
atccgcacca acgcgcagcc cggactcggt aatggcgcgc attgcgccca gcgccatctg 5520
atcgttggca accagcatcg cagtgggaac gatgccctca ttcagcattt gcatggtttg 5580
ttgaaaaccg gacatggcac tccagtcgcc ttcccgttcc gctatcggct gaatttgatt 5640
gcgagtgaga tatttatgcc agccagccag acgcagacgc gccgagacag aacttaatgg 5700
gcccgctaac agcgcgattt gctggtgacc caatgcgacc agatgctcca cgcccagtcg 5760
cgtaccgtct tcatgggaga aaataatact gttgatgggt gtctggtcag agacatcaag 5820
aaataacgcc ggaacattag tgcaggcagc ttccacagca atggcatcct ggtcatccag 5880
cggatagtta atgatcagcc cactgacgcg ttgcgcgaga agattgtgca ccgccgcttt 5940
acaggcttcg acgccgcttc gttctaccat cgacaccacc acgctggcac ccagttgatc 6000
ggcgcgagat ttaatcgccg cgacaatttg cgacggcgcg tgcagggcca gactggaggt 6060
ggcaacgcca atcagcaacg actgtttgcc cgccagttgt tgtgccacgc ggttgggaat 6120
gtaattcagc tccgccatcg ccgcttccac tttttcccgc gttttcgcag aaacgtggct 6180
ggcctggttc accacgcggg aaacggtctg ataagagaca ccggcatact ctgcgacatc 6240
gtataacgtt actggtttca cattcaccac cctgaattga ctctcttccg ggcgctatca 6300
tgccataccg cgaaaggttt tgcgccattc gatggtgtcc gggatctcga cgctctccct 6360
tatgcgactc ctgcattagg aagcagccca gtagtaggtt gaggccgttg agcaccgccg 6420
ccgcaaggaa tggtgcatgc aaggagatgg cgcccaacag tcccccggcc acggggcctg 6480
ccaccatacc cacgccgaaa caagcgctca tgagcccgaa gtggcgagcc cgatcttccc 6540
catcggtgat gtcggcgata taggcgccag caaccgcacc tgtggcgccg gtgatgccgg 6600
ccacgatgcg tccggcgtag aggatcga 6628
<210> 92
<211> 6607
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 92
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gctgaaacat 120
atttactcca accacattaa aggtaacaaa atcacagccc ctaaaccgtc aattcagggc 180
gtggtgatcc acaacgatta tggctcaatg accccttcac agtacctgcc ttggctgtac 240
gctcgcgaaa acaacggtac acatgtgaat ggctgggcct cagtgtatgc caatcgcaac 300
gaggtgctgt ggtatcatcc tacagactac gtggaatggc actgcggcaa ccaatgggcc 360
aacgccaacc tgatcggctt tgaagtttgc gaatcatatc ctggtcgcat ctcagacaaa 420
ctgtttctgg aaaacgagga agccacactg aaagtagctg ccgacgtgat gaaatcgtat 480
ggcctgcctg tgaatcgcaa cacagtgcgc ctgcacaacg aatttttcgg tacatcatgc 540
cctcatcgtt catgggacct gcacgtgggc aaaggcgagc cttataccac aacaaatatc 600
aataaaatga aagattattt cattaaacgg attaaacact actatgacgg tggcaaactg 660
gaagttagca aagcagccac cattaaacag agtgatgtta aacaagaagt gaaaaaacaa 720
gaggccaaac aaattgtgaa agccaccgat tggaaacaga acaaagatgg catctggtat 780
aaagcagaac atgccagctt taccgtgacc gcaccggaag gcattattac ccgttataaa 840
ggtccgtgga ccggtcatcc gcaggcaggc gtgctgcaga aaggtcagac catcaaatat 900
gatgaagtgc agaaatttga tggccatgtt tgggttagct gggaaacctt tgaaggtgaa 960
accgtttata tgccggttcg tacctgggat gcaaaaaccg gtaaagttgg taaactgtgg 1020
ggtgagatta aagagctccg tcgtcgtcgc cgtcggcgtc gtcgttaagg atccggctgc 1080
taacaaagcc cgaaaggaag ctgagttggc tgctgccacc gctgagcaat aactagcata 1140
accccttggg gcctctaaac gggtcttgag gggttttttg ctgaaaggag gaactatatc 1200
cggatatccc gcaagaggcc cggcagtacc ggcataacca agcctatgcc tacagcatcc 1260
agggtgacgg tgccgaggat gacgatgagc gcattgttag atttcataca cggtgcctga 1320
ctgcgttagc aatttaactg tgataaacta ccgcattaaa gctagcttat cgatgataag 1380
ctgtcaaaca tgagaattaa ttcttgaaga cgaaagggcc tcgtgatacg cctattttta 1440
taggttaatg tcatgataat aatggtttct tagacgtcag gtggcacttt tcggggaaat 1500
gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta tccgctcatg 1560
agacaataac cctgataaat gcttcaataa tattgaaaaa ggaagagtat gagtattcaa 1620
catttccgtg tcgcccttat tccctttttt gcggcatttt gccttcctgt ttttgctcac 1680
ccagaaacgc tggtgaaagt aaaagatgct gaagatcagt tgggtgcacg agtgggttac 1740
atcgaactgg atctcaacag cggtaagatc cttgagagtt ttcgccccga agaacgtttt 1800
ccaatgatga gcacttttaa agttctgcta tgtggcgcgg tattatcccg tgttgacgcc 1860
gggcaagagc aactcggtcg ccgcatacac tattctcaga atgacttggt tgagtactca 1920
ccagtcacag aaaagcatct tacggatggc atgacagtaa gagaattatg cagtgctgcc 1980
ataaccatga gtgataacac tgcggccaac ttacttctga caacgatcgg aggaccgaag 2040
gagctaaccg cttttttgca caacatgggg gatcatgtaa ctcgccttga tcgttgggaa 2100
ccggagctga atgaagccat accaaacgac gagcgtgaca ccacgatgcc tgcagcaatg 2160
gcaacaacgt tgcgcaaact attaactggc gaactactta ctctagcttc ccggcaacaa 2220
ttaatagact ggatggaggc ggataaagtt gcaggaccac ttctgcgctc ggcccttccg 2280
gctggctggt ttattgctga taaatctgga gccggtgagc gtgggtctcg cggtatcatt 2340
gcagcactgg ggccagatgg taagccctcc cgtatcgtag ttatctacac gacggggagt 2400
caggcaacta tggatgaacg aaatagacag atcgctgaga taggtgcctc actgattaag 2460
cattggtaac tgtcagacca agtttactca tatatacttt agattgattt aaaacttcat 2520
ttttaattta aaaggatcta ggtgaagatc ctttttgata atctcatgac caaaatccct 2580
taacgtgagt tttcgttcca ctgagcgtca gaccccgtag aaaagatcaa aggatcttct 2640
tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa caaaaaaacc accgctacca 2700
gcggtggttt gtttgccgga tcaagagcta ccaactcttt ttccgaaggt aactggcttc 2760
agcagagcgc agataccaaa tactgtcctt ctagtgtagc cgtagttagg ccaccacttc 2820
aagaactctg tagcaccgcc tacatacctc gctctgctaa tcctgttacc agtggctgct 2880
gccagtggcg ataagtcgtg tcttaccggg ttggactcaa gacgatagtt accggataag 2940
gcgcagcggt cgggctgaac ggggggttcg tgcacacagc ccagcttgga gcgaacgacc 3000
tacaccgaac tgagatacct acagcgtgag ctatgagaaa gcgccacgct tcccgaaggg 3060
agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa caggagagcg cacgagggag 3120
cttccagggg gaaacgcctg gtatctttat agtcctgtcg ggtttcgcca cctctgactt 3180
gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc tatggaaaaa cgccagcaac 3240
gcggcctttt tacggttcct ggccttttgc tggccttttg ctcacatgtt ctttcctgcg 3300
ttatcccctg attctgtgga taaccgtatt accgcctttg agtgagctga taccgctcgc 3360
cgcagccgaa cgaccgagcg cagcgagtca gtgagcgagg aagcggaaga gcgcctgatg 3420
cggtattttc tccttacgca tctgtgcggt atttcacacc gcaatggtgc actctcagta 3480
caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 3540
ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 3600
gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 3660
gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 3720
gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 3780
aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 3840
ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 3900
acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 3960
ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 4020
tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 4080
tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 4140
cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 4200
gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 4260
ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgcgcaccc gtggccagga 4320
cccaacgctg cccgagatgc gccgcgtgcg gctgctggag atggcggacg cgatggatat 4380
gttctgccaa gggttggttt gcgcattcac agttctccgc aagaattgat tggctccaat 4440
tcttggagtg gtgaatccgt tagcgaggtg ccgccggctt ccattcaggt cgaggtggcc 4500
cggctccatg caccgcgacg caacgcgggg aggcagacaa ggtatagggc ggcgcctaca 4560
atccatgcca acccgttcca tgtgctcgcc gaggcggcat aaatcgccgt gacgatcagc 4620
ggtccaatga tcgaagttag gctggtaaga gccgcgagcg atccttgaag ctgtccctga 4680
tggtcgtcat ctacctgcct ggacagcatg gcctgcaacg cgggcatccc gatgccgccg 4740
gaagcgagaa gaatcataat ggggaaggcc atccagcctc gcgtcgcgaa cgccagcaag 4800
acgtagccca gcgcgtcggc cgccatgccg gcgataatgg cctgcttctc gccgaaacgt 4860
ttggtggcgg gaccagtgac gaaggcttga gcgagggcgt gcaagattcc gaataccgca 4920
agcgacaggc cgatcatcgt cgcgctccag cgaaagcggt cctcgccgaa aatgacccag 4980
agcgctgccg gcacctgtcc tacgagttgc atgataaaga agacagtcat aagtgcggcg 5040
acgatagtca tgccccgcgc ccaccggaag gagctgactg ggttgaaggc tctcaagggc 5100
atcggtcgag atcccggtgc ctaatgagtg agctaactta cattaattgc gttgcgctca 5160
ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc 5220
gcggggagag gcggtttgcg tattgggcgc cagggtggtt tttcttttca ccagtgagac 5280
gggcaacagc tgattgccct tcaccgcctg gccctgagag agttgcagca agcggtccac 5340
gctggtttgc cccagcaggc gaaaatcctg tttgatggtg gttaacggcg ggatataaca 5400
tgagctgtct tcggtatcgt cgtatcccac taccgagata tccgcaccaa cgcgcagccc 5460
ggactcggta atggcgcgca ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc 5520
agtgggaacg atgccctcat tcagcatttg catggtttgt tgaaaaccgg acatggcact 5580
ccagtcgcct tcccgttccg ctatcggctg aatttgattg cgagtgagat atttatgcca 5640
gccagccaga cgcagacgcg ccgagacaga acttaatggg cccgctaaca gcgcgatttg 5700
ctggtgaccc aatgcgacca gatgctccac gcccagtcgc gtaccgtctt catgggagaa 5760
aataatactg ttgatgggtg tctggtcaga gacatcaaga aataacgccg gaacattagt 5820
gcaggcagct tccacagcaa tggcatcctg gtcatccagc ggatagttaa tgatcagccc 5880
actgacgcgt tgcgcgagaa gattgtgcac cgccgcttta caggcttcga cgccgcttcg 5940
ttctaccatc gacaccacca cgctggcacc cagttgatcg gcgcgagatt taatcgccgc 6000
gacaatttgc gacggcgcgt gcagggccag actggaggtg gcaacgccaa tcagcaacga 6060
ctgtttgccc gccagttgtt gtgccacgcg gttgggaatg taattcagct ccgccatcgc 6120
cgcttccact ttttcccgcg ttttcgcaga aacgtggctg gcctggttca ccacgcggga 6180
aacggtctga taagagacac cggcatactc tgcgacatcg tataacgtta ctggtttcac 6240
attcaccacc ctgaattgac tctcttccgg gcgctatcat gccataccgc gaaaggtttt 6300
gcgccattcg atggtgtccg ggatctcgac gctctccctt atgcgactcc tgcattagga 6360
agcagcccag tagtaggttg aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca 6420
aggagatggc gcccaacagt cccccggcca cggggcctgc caccataccc acgccgaaac 6480
aagcgctcat gagcccgaag tggcgagccc gatcttcccc atcggtgatg tcggcgatat 6540
aggcgccagc aaccgcacct gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga 6600
ggatcga 6607
<210> 93
<211> 6619
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 93
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gctgaaacat 120
atttactcca accacattaa aggtaacaaa atcacagccc ctaaaccgtc aattcagggc 180
gtggtgatcc acaacgatta tggctcaatg accccttcac agtacctgcc ttggctgtac 240
gctcgcgaaa acaacggtac acatgtgaat ggctgggcct cagtgtatgc caatcgcaac 300
gaggtgctgt ggtatcatcc tacagactac gtggaatggc actgcggcaa ccaatgggcc 360
aacgccaacc tgatcggctt tgaagtttgc gaatcatatc ctggtcgcat ctcagacaaa 420
ctgtttctgg aaaacgagga agccacactg aaagtagctg ccgacgtgat gaaatcgtat 480
ggcctgcctg tgaatcgcaa cacagtgcgc ctgcacaacg aatttttcgg tacatcatgc 540
cctcatcgtt catgggacct gcacgtgggc aaaggcgagc cttataccac aacaaatatc 600
aataaaatga aagattattt cattaaacgg attaaacact actatgacgg tggcaaactg 660
gaagttagca aagcagccac cattaaacag agtgatgtta aacaagaagt gaaaaaacaa 720
gaggccaaac aaattgtgaa agccaccgat tggaaacaga acaaagatgg catctggtat 780
aaagcagaac atgccagctt taccgtgacc gcaccggaag gcattattac ccgttataaa 840
ggtccgtgga ccggtcatcc gcaggcaggc gtgctgcaga aaggtcagac catcaaatat 900
gatgaagtgc agaaatttga tggccatgtt tgggttagct gggaaacctt tgaaggtgaa 960
accgtttata tgccggttcg tacctgggat gcaaaaaccg gtaaagttgg taaactgtgg 1020
ggtgagatta aagagctcgg tcgtaaaaaa cgtcgtcagc gtcgtcgtcc gcctcagtaa 1080
ggatccggct gctaacaaag cccgaaagga agctgagttg gctgctgcca ccgctgagca 1140
ataactagca taaccccttg gggcctctaa acgggtcttg aggggttttt tgctgaaagg 1200
aggaactata tccggatatc ccgcaagagg cccggcagta ccggcataac caagcctatg 1260
cctacagcat ccagggtgac ggtgccgagg atgacgatga gcgcattgtt agatttcata 1320
cacggtgcct gactgcgtta gcaatttaac tgtgataaac taccgcatta aagctagctt 1380
atcgatgata agctgtcaaa catgagaatt aattcttgaa gacgaaaggg cctcgtgata 1440
cgcctatttt tataggttaa tgtcatgata ataatggttt cttagacgtc aggtggcact 1500
tttcggggaa atgtgcgcgg aacccctatt tgtttatttt tctaaataca ttcaaatatg 1560
tatccgctca tgagacaata accctgataa atgcttcaat aatattgaaa aaggaagagt 1620
atgagtattc aacatttccg tgtcgccctt attccctttt ttgcggcatt ttgccttcct 1680
gtttttgctc acccagaaac gctggtgaaa gtaaaagatg ctgaagatca gttgggtgca 1740
cgagtgggtt acatcgaact ggatctcaac agcggtaaga tccttgagag ttttcgcccc 1800
gaagaacgtt ttccaatgat gagcactttt aaagttctgc tatgtggcgc ggtattatcc 1860
cgtgttgacg ccgggcaaga gcaactcggt cgccgcatac actattctca gaatgacttg 1920
gttgagtact caccagtcac agaaaagcat cttacggatg gcatgacagt aagagaatta 1980
tgcagtgctg ccataaccat gagtgataac actgcggcca acttacttct gacaacgatc 2040
ggaggaccga aggagctaac cgcttttttg cacaacatgg gggatcatgt aactcgcctt 2100
gatcgttggg aaccggagct gaatgaagcc ataccaaacg acgagcgtga caccacgatg 2160
cctgcagcaa tggcaacaac gttgcgcaaa ctattaactg gcgaactact tactctagct 2220
tcccggcaac aattaataga ctggatggag gcggataaag ttgcaggacc acttctgcgc 2280
tcggcccttc cggctggctg gtttattgct gataaatctg gagccggtga gcgtgggtct 2340
cgcggtatca ttgcagcact ggggccagat ggtaagccct cccgtatcgt agttatctac 2400
acgacgggga gtcaggcaac tatggatgaa cgaaatagac agatcgctga gataggtgcc 2460
tcactgatta agcattggta actgtcagac caagtttact catatatact ttagattgat 2520
ttaaaacttc atttttaatt taaaaggatc taggtgaaga tcctttttga taatctcatg 2580
accaaaatcc cttaacgtga gttttcgttc cactgagcgt cagaccccgt agaaaagatc 2640
aaaggatctt cttgagatcc tttttttctg cgcgtaatct gctgcttgca aacaaaaaaa 2700
ccaccgctac cagcggtggt ttgtttgccg gatcaagagc taccaactct ttttccgaag 2760
gtaactggct tcagcagagc gcagatacca aatactgtcc ttctagtgta gccgtagtta 2820
ggccaccact tcaagaactc tgtagcaccg cctacatacc tcgctctgct aatcctgtta 2880
ccagtggctg ctgccagtgg cgataagtcg tgtcttaccg ggttggactc aagacgatag 2940
ttaccggata aggcgcagcg gtcgggctga acggggggtt cgtgcacaca gcccagcttg 3000
gagcgaacga cctacaccga actgagatac ctacagcgtg agctatgaga aagcgccacg 3060
cttcccgaag ggagaaaggc ggacaggtat ccggtaagcg gcagggtcgg aacaggagag 3120
cgcacgaggg agcttccagg gggaaacgcc tggtatcttt atagtcctgt cgggtttcgc 3180
cacctctgac ttgagcgtcg atttttgtga tgctcgtcag gggggcggag cctatggaaa 3240
aacgccagca acgcggcctt tttacggttc ctggcctttt gctggccttt tgctcacatg 3300
ttctttcctg cgttatcccc tgattctgtg gataaccgta ttaccgcctt tgagtgagct 3360
gataccgctc gccgcagccg aacgaccgag cgcagcgagt cagtgagcga ggaagcggaa 3420
gagcgcctga tgcggtattt tctccttacg catctgtgcg gtatttcaca ccgcaatggt 3480
gcactctcag tacaatctgc tctgatgccg catagttaag ccagtataca ctccgctatc 3540
gctacgtgac tgggtcatgg ctgcgccccg acacccgcca acacccgctg acgcgccctg 3600
acgggcttgt ctgctcccgg catccgctta cagacaagct gtgaccgtct ccgggagctg 3660
catgtgtcag aggttttcac cgtcatcacc gaaacgcgcg aggcagctgc ggtaaagctc 3720
atcagcgtgg tcgtgaagcg attcacagat gtctgcctgt tcatccgcgt ccagctcgtt 3780
gagtttctcc agaagcgtta atgtctggct tctgataaag cgggccatgt taagggcggt 3840
tttttcctgt ttggtcactg atgcctccgt gtaaggggga tttctgttca tgggggtaat 3900
gataccgatg aaacgagaga ggatgctcac gatacgggtt actgatgatg aacatgcccg 3960
gttactggaa cgttgtgagg gtaaacaact ggcggtatgg atgcggcggg accagagaaa 4020
aatcactcag ggtcaatgcc agcgcttcgt taatacagat gtaggtgttc cacagggtag 4080
ccagcagcat cctgcgatgc agatccggaa cataatggtg cagggcgctg acttccgcgt 4140
ttccagactt tacgaaacac ggaaaccgaa gaccattcat gttgttgctc aggtcgcaga 4200
cgttttgcag cagcagtcgc ttcacgttcg ctcgcgtatc ggtgattcat tctgctaacc 4260
agtaaggcaa ccccgccagc ctagccgggt cctcaacgac aggagcacga tcatgcgcac 4320
ccgtggccag gacccaacgc tgcccgagat gcgccgcgtg cggctgctgg agatggcgga 4380
cgcgatggat atgttctgcc aagggttggt ttgcgcattc acagttctcc gcaagaattg 4440
attggctcca attcttggag tggtgaatcc gttagcgagg tgccgccggc ttccattcag 4500
gtcgaggtgg cccggctcca tgcaccgcga cgcaacgcgg ggaggcagac aaggtatagg 4560
gcggcgccta caatccatgc caacccgttc catgtgctcg ccgaggcggc ataaatcgcc 4620
gtgacgatca gcggtccaat gatcgaagtt aggctggtaa gagccgcgag cgatccttga 4680
agctgtccct gatggtcgtc atctacctgc ctggacagca tggcctgcaa cgcgggcatc 4740
ccgatgccgc cggaagcgag aagaatcata atggggaagg ccatccagcc tcgcgtcgcg 4800
aacgccagca agacgtagcc cagcgcgtcg gccgccatgc cggcgataat ggcctgcttc 4860
tcgccgaaac gtttggtggc gggaccagtg acgaaggctt gagcgagggc gtgcaagatt 4920
ccgaataccg caagcgacag gccgatcatc gtcgcgctcc agcgaaagcg gtcctcgccg 4980
aaaatgaccc agagcgctgc cggcacctgt cctacgagtt gcatgataaa gaagacagtc 5040
ataagtgcgg cgacgatagt catgccccgc gcccaccgga aggagctgac tgggttgaag 5100
gctctcaagg gcatcggtcg agatcccggt gcctaatgag tgagctaact tacattaatt 5160
gcgttgcgct cactgcccgc tttccagtcg ggaaacctgt cgtgccagct gcattaatga 5220
atcggccaac gcgcggggag aggcggtttg cgtattgggc gccagggtgg tttttctttt 5280
caccagtgag acgggcaaca gctgattgcc cttcaccgcc tggccctgag agagttgcag 5340
caagcggtcc acgctggttt gccccagcag gcgaaaatcc tgtttgatgg tggttaacgg 5400
cgggatataa catgagctgt cttcggtatc gtcgtatccc actaccgaga tatccgcacc 5460
aacgcgcagc ccggactcgg taatggcgcg cattgcgccc agcgccatct gatcgttggc 5520
aaccagcatc gcagtgggaa cgatgccctc attcagcatt tgcatggttt gttgaaaacc 5580
ggacatggca ctccagtcgc cttcccgttc cgctatcggc tgaatttgat tgcgagtgag 5640
atatttatgc cagccagcca gacgcagacg cgccgagaca gaacttaatg ggcccgctaa 5700
cagcgcgatt tgctggtgac ccaatgcgac cagatgctcc acgcccagtc gcgtaccgtc 5760
ttcatgggag aaaataatac tgttgatggg tgtctggtca gagacatcaa gaaataacgc 5820
cggaacatta gtgcaggcag cttccacagc aatggcatcc tggtcatcca gcggatagtt 5880
aatgatcagc ccactgacgc gttgcgcgag aagattgtgc accgccgctt tacaggcttc 5940
gacgccgctt cgttctacca tcgacaccac cacgctggca cccagttgat cggcgcgaga 6000
tttaatcgcc gcgacaattt gcgacggcgc gtgcagggcc agactggagg tggcaacgcc 6060
aatcagcaac gactgtttgc ccgccagttg ttgtgccacg cggttgggaa tgtaattcag 6120
ctccgccatc gccgcttcca ctttttcccg cgttttcgca gaaacgtggc tggcctggtt 6180
caccacgcgg gaaacggtct gataagagac accggcatac tctgcgacat cgtataacgt 6240
tactggtttc acattcacca ccctgaattg actctcttcc gggcgctatc atgccatacc 6300
gcgaaaggtt ttgcgccatt cgatggtgtc cgggatctcg acgctctccc ttatgcgact 6360
cctgcattag gaagcagccc agtagtaggt tgaggccgtt gagcaccgcc gccgcaagga 6420
atggtgcatg caaggagatg gcgcccaaca gtcccccggc cacggggcct gccaccatac 6480
ccacgccgaa acaagcgctc atgagcccga agtggcgagc ccgatcttcc ccatcggtga 6540
tgtcggcgat ataggcgcca gcaaccgcac ctgtggcgcc ggtgatgccg gccacgatgc 6600
gtccggcgta gaggatcga 6619
<210> 94
<211> 6247
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 94
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gctgaaacat 120
atttactcca accacattaa aggtaacaaa atcacagccc ctaaaccgtc aattcagggc 180
gtggtgatcc acaacgatta tggctcaatg accccttcac agtacctgcc ttggctgtac 240
gctcgcgaaa acaacggtac acatgtgaat ggctgggcct cagtgtatgc caatcgcaac 300
gaggtgctgt ggtatcatcc tacagactac gtggaatggc actgcggcaa ccaatgggcc 360
aacgccaacc tgatcggctt tgaagtttgc gaatcatatc ctggtcgcat ctcagacaaa 420
ctgtttctgg aaaacgagga agccacactg aaagtagctg ccgacgtgat gaaatcgtat 480
ggcctgcctg tgaatcgcaa cacagtgcgc ctgcacaacg aatttttcgg tacatcatgc 540
cctcatcgtt catgggacct gcacgtgggc aaaggcgagc cttataccac aacaaatatc 600
aataaaatga aagattattt cattaaacgg attaaacact actatgacgg tgagctccgc 660
cagatcaaaa tttggtttca gaatcgtcgc atgaaatgga aaaaataagg atccggctgc 720
taacaaagcc cgaaaggaag ctgagttggc tgctgccacc gctgagcaat aactagcata 780
accccttggg gcctctaaac gggtcttgag gggttttttg ctgaaaggag gaactatatc 840
cggatatccc gcaagaggcc cggcagtacc ggcataacca agcctatgcc tacagcatcc 900
agggtgacgg tgccgaggat gacgatgagc gcattgttag atttcataca cggtgcctga 960
ctgcgttagc aatttaactg tgataaacta ccgcattaaa gctagcttat cgatgataag 1020
ctgtcaaaca tgagaattaa ttcttgaaga cgaaagggcc tcgtgatacg cctattttta 1080
taggttaatg tcatgataat aatggtttct tagacgtcag gtggcacttt tcggggaaat 1140
gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta tccgctcatg 1200
agacaataac cctgataaat gcttcaataa tattgaaaaa ggaagagtat gagtattcaa 1260
catttccgtg tcgcccttat tccctttttt gcggcatttt gccttcctgt ttttgctcac 1320
ccagaaacgc tggtgaaagt aaaagatgct gaagatcagt tgggtgcacg agtgggttac 1380
atcgaactgg atctcaacag cggtaagatc cttgagagtt ttcgccccga agaacgtttt 1440
ccaatgatga gcacttttaa agttctgcta tgtggcgcgg tattatcccg tgttgacgcc 1500
gggcaagagc aactcggtcg ccgcatacac tattctcaga atgacttggt tgagtactca 1560
ccagtcacag aaaagcatct tacggatggc atgacagtaa gagaattatg cagtgctgcc 1620
ataaccatga gtgataacac tgcggccaac ttacttctga caacgatcgg aggaccgaag 1680
gagctaaccg cttttttgca caacatgggg gatcatgtaa ctcgccttga tcgttgggaa 1740
ccggagctga atgaagccat accaaacgac gagcgtgaca ccacgatgcc tgcagcaatg 1800
gcaacaacgt tgcgcaaact attaactggc gaactactta ctctagcttc ccggcaacaa 1860
ttaatagact ggatggaggc ggataaagtt gcaggaccac ttctgcgctc ggcccttccg 1920
gctggctggt ttattgctga taaatctgga gccggtgagc gtgggtctcg cggtatcatt 1980
gcagcactgg ggccagatgg taagccctcc cgtatcgtag ttatctacac gacggggagt 2040
caggcaacta tggatgaacg aaatagacag atcgctgaga taggtgcctc actgattaag 2100
cattggtaac tgtcagacca agtttactca tatatacttt agattgattt aaaacttcat 2160
ttttaattta aaaggatcta ggtgaagatc ctttttgata atctcatgac caaaatccct 2220
taacgtgagt tttcgttcca ctgagcgtca gaccccgtag aaaagatcaa aggatcttct 2280
tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa caaaaaaacc accgctacca 2340
gcggtggttt gtttgccgga tcaagagcta ccaactcttt ttccgaaggt aactggcttc 2400
agcagagcgc agataccaaa tactgtcctt ctagtgtagc cgtagttagg ccaccacttc 2460
aagaactctg tagcaccgcc tacatacctc gctctgctaa tcctgttacc agtggctgct 2520
gccagtggcg ataagtcgtg tcttaccggg ttggactcaa gacgatagtt accggataag 2580
gcgcagcggt cgggctgaac ggggggttcg tgcacacagc ccagcttgga gcgaacgacc 2640
tacaccgaac tgagatacct acagcgtgag ctatgagaaa gcgccacgct tcccgaaggg 2700
agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa caggagagcg cacgagggag 2760
cttccagggg gaaacgcctg gtatctttat agtcctgtcg ggtttcgcca cctctgactt 2820
gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc tatggaaaaa cgccagcaac 2880
gcggcctttt tacggttcct ggccttttgc tggccttttg ctcacatgtt ctttcctgcg 2940
ttatcccctg attctgtgga taaccgtatt accgcctttg agtgagctga taccgctcgc 3000
cgcagccgaa cgaccgagcg cagcgagtca gtgagcgagg aagcggaaga gcgcctgatg 3060
cggtattttc tccttacgca tctgtgcggt atttcacacc gcaatggtgc actctcagta 3120
caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 3180
ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 3240
gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 3300
gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 3360
gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 3420
aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 3480
ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 3540
acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 3600
ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 3660
tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 3720
tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3780
cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3840
gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3900
ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgcgcaccc gtggccagga 3960
cccaacgctg cccgagatgc gccgcgtgcg gctgctggag atggcggacg cgatggatat 4020
gttctgccaa gggttggttt gcgcattcac agttctccgc aagaattgat tggctccaat 4080
tcttggagtg gtgaatccgt tagcgaggtg ccgccggctt ccattcaggt cgaggtggcc 4140
cggctccatg caccgcgacg caacgcgggg aggcagacaa ggtatagggc ggcgcctaca 4200
atccatgcca acccgttcca tgtgctcgcc gaggcggcat aaatcgccgt gacgatcagc 4260
ggtccaatga tcgaagttag gctggtaaga gccgcgagcg atccttgaag ctgtccctga 4320
tggtcgtcat ctacctgcct ggacagcatg gcctgcaacg cgggcatccc gatgccgccg 4380
gaagcgagaa gaatcataat ggggaaggcc atccagcctc gcgtcgcgaa cgccagcaag 4440
acgtagccca gcgcgtcggc cgccatgccg gcgataatgg cctgcttctc gccgaaacgt 4500
ttggtggcgg gaccagtgac gaaggcttga gcgagggcgt gcaagattcc gaataccgca 4560
agcgacaggc cgatcatcgt cgcgctccag cgaaagcggt cctcgccgaa aatgacccag 4620
agcgctgccg gcacctgtcc tacgagttgc atgataaaga agacagtcat aagtgcggcg 4680
acgatagtca tgccccgcgc ccaccggaag gagctgactg ggttgaaggc tctcaagggc 4740
atcggtcgag atcccggtgc ctaatgagtg agctaactta cattaattgc gttgcgctca 4800
ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc 4860
gcggggagag gcggtttgcg tattgggcgc cagggtggtt tttcttttca ccagtgagac 4920
gggcaacagc tgattgccct tcaccgcctg gccctgagag agttgcagca agcggtccac 4980
gctggtttgc cccagcaggc gaaaatcctg tttgatggtg gttaacggcg ggatataaca 5040
tgagctgtct tcggtatcgt cgtatcccac taccgagata tccgcaccaa cgcgcagccc 5100
ggactcggta atggcgcgca ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc 5160
agtgggaacg atgccctcat tcagcatttg catggtttgt tgaaaaccgg acatggcact 5220
ccagtcgcct tcccgttccg ctatcggctg aatttgattg cgagtgagat atttatgcca 5280
gccagccaga cgcagacgcg ccgagacaga acttaatggg cccgctaaca gcgcgatttg 5340
ctggtgaccc aatgcgacca gatgctccac gcccagtcgc gtaccgtctt catgggagaa 5400
aataatactg ttgatgggtg tctggtcaga gacatcaaga aataacgccg gaacattagt 5460
gcaggcagct tccacagcaa tggcatcctg gtcatccagc ggatagttaa tgatcagccc 5520
actgacgcgt tgcgcgagaa gattgtgcac cgccgcttta caggcttcga cgccgcttcg 5580
ttctaccatc gacaccacca cgctggcacc cagttgatcg gcgcgagatt taatcgccgc 5640
gacaatttgc gacggcgcgt gcagggccag actggaggtg gcaacgccaa tcagcaacga 5700
ctgtttgccc gccagttgtt gtgccacgcg gttgggaatg taattcagct ccgccatcgc 5760
cgcttccact ttttcccgcg ttttcgcaga aacgtggctg gcctggttca ccacgcggga 5820
aacggtctga taagagacac cggcatactc tgcgacatcg tataacgtta ctggtttcac 5880
attcaccacc ctgaattgac tctcttccgg gcgctatcat gccataccgc gaaaggtttt 5940
gcgccattcg atggtgtccg ggatctcgac gctctccctt atgcgactcc tgcattagga 6000
agcagcccag tagtaggttg aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca 6060
aggagatggc gcccaacagt cccccggcca cggggcctgc caccataccc acgccgaaac 6120
aagcgctcat gagcccgaag tggcgagccc gatcttcccc atcggtgatg tcggcgatat 6180
aggcgccagc aaccgcacct gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga 6240
ggatcga 6247
<210> 95
<211> 6226
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 95
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gctgaaacat 120
atttactcca accacattaa aggtaacaaa atcacagccc ctaaaccgtc aattcagggc 180
gtggtgatcc acaacgatta tggctcaatg accccttcac agtacctgcc ttggctgtac 240
gctcgcgaaa acaacggtac acatgtgaat ggctgggcct cagtgtatgc caatcgcaac 300
gaggtgctgt ggtatcatcc tacagactac gtggaatggc actgcggcaa ccaatgggcc 360
aacgccaacc tgatcggctt tgaagtttgc gaatcatatc ctggtcgcat ctcagacaaa 420
ctgtttctgg aaaacgagga agccacactg aaagtagctg ccgacgtgat gaaatcgtat 480
ggcctgcctg tgaatcgcaa cacagtgcgc ctgcacaacg aatttttcgg tacatcatgc 540
cctcatcgtt catgggacct gcacgtgggc aaaggcgagc cttataccac aacaaatatc 600
aataaaatga aagattattt cattaaacgg attaaacact actatgacgg tgagctccgt 660
cgtcgtcgcc gtcggcgtcg tcgttaagga tccggctgct aacaaagccc gaaaggaagc 720
tgagttggct gctgccaccg ctgagcaata actagcataa ccccttgggg cctctaaacg 780
ggtcttgagg ggttttttgc tgaaaggagg aactatatcc ggatatcccg caagaggccc 840
ggcagtaccg gcataaccaa gcctatgcct acagcatcca gggtgacggt gccgaggatg 900
acgatgagcg cattgttaga tttcatacac ggtgcctgac tgcgttagca atttaactgt 960
gataaactac cgcattaaag ctagcttatc gatgataagc tgtcaaacat gagaattaat 1020
tcttgaagac gaaagggcct cgtgatacgc ctatttttat aggttaatgt catgataata 1080
atggtttctt agacgtcagg tggcactttt cggggaaatg tgcgcggaac ccctatttgt 1140
ttatttttct aaatacattc aaatatgtat ccgctcatga gacaataacc ctgataaatg 1200
cttcaataat attgaaaaag gaagagtatg agtattcaac atttccgtgt cgcccttatt 1260
cccttttttg cggcattttg ccttcctgtt tttgctcacc cagaaacgct ggtgaaagta 1320
aaagatgctg aagatcagtt gggtgcacga gtgggttaca tcgaactgga tctcaacagc 1380
ggtaagatcc ttgagagttt tcgccccgaa gaacgttttc caatgatgag cacttttaaa 1440
gttctgctat gtggcgcggt attatcccgt gttgacgccg ggcaagagca actcggtcgc 1500
cgcatacact attctcagaa tgacttggtt gagtactcac cagtcacaga aaagcatctt 1560
acggatggca tgacagtaag agaattatgc agtgctgcca taaccatgag tgataacact 1620
gcggccaact tacttctgac aacgatcgga ggaccgaagg agctaaccgc ttttttgcac 1680
aacatggggg atcatgtaac tcgccttgat cgttgggaac cggagctgaa tgaagccata 1740
ccaaacgacg agcgtgacac cacgatgcct gcagcaatgg caacaacgtt gcgcaaacta 1800
ttaactggcg aactacttac tctagcttcc cggcaacaat taatagactg gatggaggcg 1860
gataaagttg caggaccact tctgcgctcg gcccttccgg ctggctggtt tattgctgat 1920
aaatctggag ccggtgagcg tgggtctcgc ggtatcattg cagcactggg gccagatggt 1980
aagccctccc gtatcgtagt tatctacacg acggggagtc aggcaactat ggatgaacga 2040
aatagacaga tcgctgagat aggtgcctca ctgattaagc attggtaact gtcagaccaa 2100
gtttactcat atatacttta gattgattta aaacttcatt tttaatttaa aaggatctag 2160
gtgaagatcc tttttgataa tctcatgacc aaaatccctt aacgtgagtt ttcgttccac 2220
tgagcgtcag accccgtaga aaagatcaaa ggatcttctt gagatccttt ttttctgcgc 2280
gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag cggtggtttg tttgccggat 2340
caagagctac caactctttt tccgaaggta actggcttca gcagagcgca gataccaaat 2400
actgtccttc tagtgtagcc gtagttaggc caccacttca agaactctgt agcaccgcct 2460
acatacctcg ctctgctaat cctgttacca gtggctgctg ccagtggcga taagtcgtgt 2520
cttaccgggt tggactcaag acgatagtta ccggataagg cgcagcggtc gggctgaacg 2580
gggggttcgt gcacacagcc cagcttggag cgaacgacct acaccgaact gagataccta 2640
cagcgtgagc tatgagaaag cgccacgctt cccgaaggga gaaaggcgga caggtatccg 2700
gtaagcggca gggtcggaac aggagagcgc acgagggagc ttccaggggg aaacgcctgg 2760
tatctttata gtcctgtcgg gtttcgccac ctctgacttg agcgtcgatt tttgtgatgc 2820
tcgtcagggg ggcggagcct atggaaaaac gccagcaacg cggccttttt acggttcctg 2880
gccttttgct ggccttttgc tcacatgttc tttcctgcgt tatcccctga ttctgtggat 2940
aaccgtatta ccgcctttga gtgagctgat accgctcgcc gcagccgaac gaccgagcgc 3000
agcgagtcag tgagcgagga agcggaagag cgcctgatgc ggtattttct ccttacgcat 3060
ctgtgcggta tttcacaccg caatggtgca ctctcagtac aatctgctct gatgccgcat 3120
agttaagcca gtatacactc cgctatcgct acgtgactgg gtcatggctg cgccccgaca 3180
cccgccaaca cccgctgacg cgccctgacg ggcttgtctg ctcccggcat ccgcttacag 3240
acaagctgtg accgtctccg ggagctgcat gtgtcagagg ttttcaccgt catcaccgaa 3300
acgcgcgagg cagctgcggt aaagctcatc agcgtggtcg tgaagcgatt cacagatgtc 3360
tgcctgttca tccgcgtcca gctcgttgag tttctccaga agcgttaatg tctggcttct 3420
gataaagcgg gccatgttaa gggcggtttt ttcctgtttg gtcactgatg cctccgtgta 3480
agggggattt ctgttcatgg gggtaatgat accgatgaaa cgagagagga tgctcacgat 3540
acgggttact gatgatgaac atgcccggtt actggaacgt tgtgagggta aacaactggc 3600
ggtatggatg cggcgggacc agagaaaaat cactcagggt caatgccagc gcttcgttaa 3660
tacagatgta ggtgttccac agggtagcca gcagcatcct gcgatgcaga tccggaacat 3720
aatggtgcag ggcgctgact tccgcgtttc cagactttac gaaacacgga aaccgaagac 3780
cattcatgtt gttgctcagg tcgcagacgt tttgcagcag cagtcgcttc acgttcgctc 3840
gcgtatcggt gattcattct gctaaccagt aaggcaaccc cgccagccta gccgggtcct 3900
caacgacagg agcacgatca tgcgcacccg tggccaggac ccaacgctgc ccgagatgcg 3960
ccgcgtgcgg ctgctggaga tggcggacgc gatggatatg ttctgccaag ggttggtttg 4020
cgcattcaca gttctccgca agaattgatt ggctccaatt cttggagtgg tgaatccgtt 4080
agcgaggtgc cgccggcttc cattcaggtc gaggtggccc ggctccatgc accgcgacgc 4140
aacgcgggga ggcagacaag gtatagggcg gcgcctacaa tccatgccaa cccgttccat 4200
gtgctcgccg aggcggcata aatcgccgtg acgatcagcg gtccaatgat cgaagttagg 4260
ctggtaagag ccgcgagcga tccttgaagc tgtccctgat ggtcgtcatc tacctgcctg 4320
gacagcatgg cctgcaacgc gggcatcccg atgccgccgg aagcgagaag aatcataatg 4380
gggaaggcca tccagcctcg cgtcgcgaac gccagcaaga cgtagcccag cgcgtcggcc 4440
gccatgccgg cgataatggc ctgcttctcg ccgaaacgtt tggtggcggg accagtgacg 4500
aaggcttgag cgagggcgtg caagattccg aataccgcaa gcgacaggcc gatcatcgtc 4560
gcgctccagc gaaagcggtc ctcgccgaaa atgacccaga gcgctgccgg cacctgtcct 4620
acgagttgca tgataaagaa gacagtcata agtgcggcga cgatagtcat gccccgcgcc 4680
caccggaagg agctgactgg gttgaaggct ctcaagggca tcggtcgaga tcccggtgcc 4740
taatgagtga gctaacttac attaattgcg ttgcgctcac tgcccgcttt ccagtcggga 4800
aacctgtcgt gccagctgca ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt 4860
attgggcgcc agggtggttt ttcttttcac cagtgagacg ggcaacagct gattgccctt 4920
caccgcctgg ccctgagaga gttgcagcaa gcggtccacg ctggtttgcc ccagcaggcg 4980
aaaatcctgt ttgatggtgg ttaacggcgg gatataacat gagctgtctt cggtatcgtc 5040
gtatcccact accgagatat ccgcaccaac gcgcagcccg gactcggtaa tggcgcgcat 5100
tgcgcccagc gccatctgat cgttggcaac cagcatcgca gtgggaacga tgccctcatt 5160
cagcatttgc atggtttgtt gaaaaccgga catggcactc cagtcgcctt cccgttccgc 5220
tatcggctga atttgattgc gagtgagata tttatgccag ccagccagac gcagacgcgc 5280
cgagacagaa cttaatgggc ccgctaacag cgcgatttgc tggtgaccca atgcgaccag 5340
atgctccacg cccagtcgcg taccgtcttc atgggagaaa ataatactgt tgatgggtgt 5400
ctggtcagag acatcaagaa ataacgccgg aacattagtg caggcagctt ccacagcaat 5460
ggcatcctgg tcatccagcg gatagttaat gatcagccca ctgacgcgtt gcgcgagaag 5520
attgtgcacc gccgctttac aggcttcgac gccgcttcgt tctaccatcg acaccaccac 5580
gctggcaccc agttgatcgg cgcgagattt aatcgccgcg acaatttgcg acggcgcgtg 5640
cagggccaga ctggaggtgg caacgccaat cagcaacgac tgtttgcccg ccagttgttg 5700
tgccacgcgg ttgggaatgt aattcagctc cgccatcgcc gcttccactt tttcccgcgt 5760
tttcgcagaa acgtggctgg cctggttcac cacgcgggaa acggtctgat aagagacacc 5820
ggcatactct gcgacatcgt ataacgttac tggtttcaca ttcaccaccc tgaattgact 5880
ctcttccggg cgctatcatg ccataccgcg aaaggttttg cgccattcga tggtgtccgg 5940
gatctcgacg ctctccctta tgcgactcct gcattaggaa gcagcccagt agtaggttga 6000
ggccgttgag caccgccgcc gcaaggaatg gtgcatgcaa ggagatggcg cccaacagtc 6060
ccccggccac ggggcctgcc accataccca cgccgaaaca agcgctcatg agcccgaagt 6120
ggcgagcccg atcttcccca tcggtgatgt cggcgatata ggcgccagca accgcacctg 6180
tggcgccggt gatgccggcc acgatgcgtc cggcgtagag gatcga 6226
<210> 96
<211> 6238
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 96
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gctgaaacat 120
atttactcca accacattaa aggtaacaaa atcacagccc ctaaaccgtc aattcagggc 180
gtggtgatcc acaacgatta tggctcaatg accccttcac agtacctgcc ttggctgtac 240
gctcgcgaaa acaacggtac acatgtgaat ggctgggcct cagtgtatgc caatcgcaac 300
gaggtgctgt ggtatcatcc tacagactac gtggaatggc actgcggcaa ccaatgggcc 360
aacgccaacc tgatcggctt tgaagtttgc gaatcatatc ctggtcgcat ctcagacaaa 420
ctgtttctgg aaaacgagga agccacactg aaagtagctg ccgacgtgat gaaatcgtat 480
ggcctgcctg tgaatcgcaa cacagtgcgc ctgcacaacg aatttttcgg tacatcatgc 540
cctcatcgtt catgggacct gcacgtgggc aaaggcgagc cttataccac aacaaatatc 600
aataaaatga aagattattt cattaaacgg attaaacact actatgacgg tgagctcggt 660
cgtaaaaaac gtcgtcagcg tcgtcgtccg cctcagtaag gatccggctg ctaacaaagc 720
ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg 780
ggcctctaaa cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggatatcc 840
cgcaagaggc ccggcagtac cggcataacc aagcctatgc ctacagcatc cagggtgacg 900
gtgccgagga tgacgatgag cgcattgtta gatttcatac acggtgcctg actgcgttag 960
caatttaact gtgataaact accgcattaa agctagctta tcgatgataa gctgtcaaac 1020
atgagaatta attcttgaag acgaaagggc ctcgtgatac gcctattttt ataggttaat 1080
gtcatgataa taatggtttc ttagacgtca ggtggcactt ttcggggaaa tgtgcgcgga 1140
acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat gagacaataa 1200
ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca acatttccgt 1260
gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca cccagaaacg 1320
ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta catcgaactg 1380
gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt tccaatgatg 1440
agcactttta aagttctgct atgtggcgcg gtattatccc gtgttgacgc cgggcaagag 1500
caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc accagtcaca 1560
gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc cataaccatg 1620
agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa ggagctaacc 1680
gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga accggagctg 1740
aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgcagcaat ggcaacaacg 1800
ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca attaatagac 1860
tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc ggctggctgg 1920
tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat tgcagcactg 1980
gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag tcaggcaact 2040
atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa gcattggtaa 2100
ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca tttttaattt 2160
aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc ttaacgtgag 2220
ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc ttgagatcct 2280
ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt 2340
tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt cagcagagcg 2400
cagataccaa atactgtcct tctagtgtag ccgtagttag gccaccactt caagaactct 2460
gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc tgccagtggc 2520
gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa ggcgcagcgg 2580
tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa 2640
ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg 2700
gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg 2760
ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact tgagcgtcga 2820
tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa cgcggccttt 2880
ttacggttcc tggccttttg ctggcctttt gctcacatgt tctttcctgc gttatcccct 2940
gattctgtgg ataaccgtat taccgccttt gagtgagctg ataccgctcg ccgcagccga 3000
acgaccgagc gcagcgagtc agtgagcgag gaagcggaag agcgcctgat gcggtatttt 3060
ctccttacgc atctgtgcgg tatttcacac cgcaatggtg cactctcagt acaatctgct 3120
ctgatgccgc atagttaagc cagtatacac tccgctatcg ctacgtgact gggtcatggc 3180
tgcgccccga cacccgccaa cacccgctga cgcgccctga cgggcttgtc tgctcccggc 3240
atccgcttac agacaagctg tgaccgtctc cgggagctgc atgtgtcaga ggttttcacc 3300
gtcatcaccg aaacgcgcga ggcagctgcg gtaaagctca tcagcgtggt cgtgaagcga 3360
ttcacagatg tctgcctgtt catccgcgtc cagctcgttg agtttctcca gaagcgttaa 3420
tgtctggctt ctgataaagc gggccatgtt aagggcggtt ttttcctgtt tggtcactga 3480
tgcctccgtg taagggggat ttctgttcat gggggtaatg ataccgatga aacgagagag 3540
gatgctcacg atacgggtta ctgatgatga acatgcccgg ttactggaac gttgtgaggg 3600
taaacaactg gcggtatgga tgcggcggga ccagagaaaa atcactcagg gtcaatgcca 3660
gcgcttcgtt aatacagatg taggtgttcc acagggtagc cagcagcatc ctgcgatgca 3720
gatccggaac ataatggtgc agggcgctga cttccgcgtt tccagacttt acgaaacacg 3780
gaaaccgaag accattcatg ttgttgctca ggtcgcagac gttttgcagc agcagtcgct 3840
tcacgttcgc tcgcgtatcg gtgattcatt ctgctaacca gtaaggcaac cccgccagcc 3900
tagccgggtc ctcaacgaca ggagcacgat catgcgcacc cgtggccagg acccaacgct 3960
gcccgagatg cgccgcgtgc ggctgctgga gatggcggac gcgatggata tgttctgcca 4020
agggttggtt tgcgcattca cagttctccg caagaattga ttggctccaa ttcttggagt 4080
ggtgaatccg ttagcgaggt gccgccggct tccattcagg tcgaggtggc ccggctccat 4140
gcaccgcgac gcaacgcggg gaggcagaca aggtataggg cggcgcctac aatccatgcc 4200
aacccgttcc atgtgctcgc cgaggcggca taaatcgccg tgacgatcag cggtccaatg 4260
atcgaagtta ggctggtaag agccgcgagc gatccttgaa gctgtccctg atggtcgtca 4320
tctacctgcc tggacagcat ggcctgcaac gcgggcatcc cgatgccgcc ggaagcgaga 4380
agaatcataa tggggaaggc catccagcct cgcgtcgcga acgccagcaa gacgtagccc 4440
agcgcgtcgg ccgccatgcc ggcgataatg gcctgcttct cgccgaaacg tttggtggcg 4500
ggaccagtga cgaaggcttg agcgagggcg tgcaagattc cgaataccgc aagcgacagg 4560
ccgatcatcg tcgcgctcca gcgaaagcgg tcctcgccga aaatgaccca gagcgctgcc 4620
ggcacctgtc ctacgagttg catgataaag aagacagtca taagtgcggc gacgatagtc 4680
atgccccgcg cccaccggaa ggagctgact gggttgaagg ctctcaaggg catcggtcga 4740
gatcccggtg cctaatgagt gagctaactt acattaattg cgttgcgctc actgcccgct 4800
ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg cgcggggaga 4860
ggcggtttgc gtattgggcg ccagggtggt ttttcttttc accagtgaga cgggcaacag 4920
ctgattgccc ttcaccgcct ggccctgaga gagttgcagc aagcggtcca cgctggtttg 4980
ccccagcagg cgaaaatcct gtttgatggt ggttaacggc gggatataac atgagctgtc 5040
ttcggtatcg tcgtatccca ctaccgagat atccgcacca acgcgcagcc cggactcggt 5100
aatggcgcgc attgcgccca gcgccatctg atcgttggca accagcatcg cagtgggaac 5160
gatgccctca ttcagcattt gcatggtttg ttgaaaaccg gacatggcac tccagtcgcc 5220
ttcccgttcc gctatcggct gaatttgatt gcgagtgaga tatttatgcc agccagccag 5280
acgcagacgc gccgagacag aacttaatgg gcccgctaac agcgcgattt gctggtgacc 5340
caatgcgacc agatgctcca cgcccagtcg cgtaccgtct tcatgggaga aaataatact 5400
gttgatgggt gtctggtcag agacatcaag aaataacgcc ggaacattag tgcaggcagc 5460
ttccacagca atggcatcct ggtcatccag cggatagtta atgatcagcc cactgacgcg 5520
ttgcgcgaga agattgtgca ccgccgcttt acaggcttcg acgccgcttc gttctaccat 5580
cgacaccacc acgctggcac ccagttgatc ggcgcgagat ttaatcgccg cgacaatttg 5640
cgacggcgcg tgcagggcca gactggaggt ggcaacgcca atcagcaacg actgtttgcc 5700
cgccagttgt tgtgccacgc ggttgggaat gtaattcagc tccgccatcg ccgcttccac 5760
tttttcccgc gttttcgcag aaacgtggct ggcctggttc accacgcggg aaacggtctg 5820
ataagagaca ccggcatact ctgcgacatc gtataacgtt actggtttca cattcaccac 5880
cctgaattga ctctcttccg ggcgctatca tgccataccg cgaaaggttt tgcgccattc 5940
gatggtgtcc gggatctcga cgctctccct tatgcgactc ctgcattagg aagcagccca 6000
gtagtaggtt gaggccgttg agcaccgccg ccgcaaggaa tggtgcatgc aaggagatgg 6060
cgcccaacag tcccccggcc acggggcctg ccaccatacc cacgccgaaa caagcgctca 6120
tgagcccgaa gtggcgagcc cgatcttccc catcggtgat gtcggcgata taggcgccag 6180
caaccgcacc tgtggcgccg gtgatgccgg ccacgatgcg tccggcgtag aggatcga 6238
<210> 97
<211> 6571
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 97
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gtccattatc 120
atggaagtgg ccacaatgca agccaaactg acaaaaaatg agttcattga gtggctgaaa 180
acgtccgagg gtaaacagtt caacgtggac ctgtggtacg gttttcagtg tttcgactac 240
gccaacgctg gctggaaagt gctgttcggc ctgctgctga aaggcctggg agccaaagac 300
atcccttttg caaacaattt cgatggcctg gccacagttt atcaaaacac ccctgacttt 360
ctggcccaac caggcgacat ggtggtgttt ggttctaatt atggcgcagg ctatggccac 420
gtagcctggg tgatcgaagc cacactggac tacattattg tttatgagca aaactggctg 480
ggaggcggat ggacagacgg catcgaacag cctggctggg gctgggagaa agtgacacgc 540
cgtcaacatg cctatgactt ccctatgtgg ttcatccgtc ctaatttcaa aggtggtaaa 600
ctggaagtta gcaaagcagc aaccattaaa cagtccgatg ttaaacaaga agtgaaaaaa 660
caagaggcca aacaaattgt gaaagccacc gattggaaac agaacaaaga tggcatttgg 720
tataaagcag aacatgccag ctttaccgtt accgcaccgg aaggcattat tacccgttat 780
aaaggtccgt ggaccggtca tccgcaggca ggcgtactgc agaaaggtca gaccattaaa 840
tacgatgaag tgcagaaatt tgatggccat gtttgggtta gctgggaaac ctttgaaggt 900
gaaaccgttt atatgccggt tcgtacctgg gatgcaaaaa ccggtaaagt gggcaaactg 960
tggggtgaaa tcaaagagct ccgccagatc aaaatttggt ttcagaatcg tcgcatgaaa 1020
tggaaaaaat aaggatccgg ctgctaacaa agcccgaaag gaagctgagt tggctgctgc 1080
caccgctgag caataactag cataacccct tggggcctct aaacgggtct tgaggggttt 1140
tttgctgaaa ggaggaacta tatccggata tcccgcaaga ggcccggcag taccggcata 1200
accaagccta tgcctacagc atccagggtg acggtgccga ggatgacgat gagcgcattg 1260
ttagatttca tacacggtgc ctgactgcgt tagcaattta actgtgataa actaccgcat 1320
taaagctagc ttatcgatga taagctgtca aacatgagaa ttaattcttg aagacgaaag 1380
ggcctcgtga tacgcctatt tttataggtt aatgtcatga taataatggt ttcttagacg 1440
tcaggtggca cttttcgggg aaatgtgcgc ggaaccccta tttgtttatt tttctaaata 1500
cattcaaata tgtatccgct catgagacaa taaccctgat aaatgcttca ataatattga 1560
aaaaggaaga gtatgagtat tcaacatttc cgtgtcgccc ttattccctt ttttgcggca 1620
ttttgccttc ctgtttttgc tcacccagaa acgctggtga aagtaaaaga tgctgaagat 1680
cagttgggtg cacgagtggg ttacatcgaa ctggatctca acagcggtaa gatccttgag 1740
agttttcgcc ccgaagaacg ttttccaatg atgagcactt ttaaagttct gctatgtggc 1800
gcggtattat cccgtgttga cgccgggcaa gagcaactcg gtcgccgcat acactattct 1860
cagaatgact tggttgagta ctcaccagtc acagaaaagc atcttacgga tggcatgaca 1920
gtaagagaat tatgcagtgc tgccataacc atgagtgata acactgcggc caacttactt 1980
ctgacaacga tcggaggacc gaaggagcta accgcttttt tgcacaacat gggggatcat 2040
gtaactcgcc ttgatcgttg ggaaccggag ctgaatgaag ccataccaaa cgacgagcgt 2100
gacaccacga tgcctgcagc aatggcaaca acgttgcgca aactattaac tggcgaacta 2160
cttactctag cttcccggca acaattaata gactggatgg aggcggataa agttgcagga 2220
ccacttctgc gctcggccct tccggctggc tggtttattg ctgataaatc tggagccggt 2280
gagcgtgggt ctcgcggtat cattgcagca ctggggccag atggtaagcc ctcccgtatc 2340
gtagttatct acacgacggg gagtcaggca actatggatg aacgaaatag acagatcgct 2400
gagataggtg cctcactgat taagcattgg taactgtcag accaagttta ctcatatata 2460
ctttagattg atttaaaact tcatttttaa tttaaaagga tctaggtgaa gatccttttt 2520
gataatctca tgaccaaaat cccttaacgt gagttttcgt tccactgagc gtcagacccc 2580
gtagaaaaga tcaaaggatc ttcttgagat cctttttttc tgcgcgtaat ctgctgcttg 2640
caaacaaaaa aaccaccgct accagcggtg gtttgtttgc cggatcaaga gctaccaact 2700
ctttttccga aggtaactgg cttcagcaga gcgcagatac caaatactgt ccttctagtg 2760
tagccgtagt taggccacca cttcaagaac tctgtagcac cgcctacata cctcgctctg 2820
ctaatcctgt taccagtggc tgctgccagt ggcgataagt cgtgtcttac cgggttggac 2880
tcaagacgat agttaccgga taaggcgcag cggtcgggct gaacgggggg ttcgtgcaca 2940
cagcccagct tggagcgaac gacctacacc gaactgagat acctacagcg tgagctatga 3000
gaaagcgcca cgcttcccga agggagaaag gcggacaggt atccggtaag cggcagggtc 3060
ggaacaggag agcgcacgag ggagcttcca gggggaaacg cctggtatct ttatagtcct 3120
gtcgggtttc gccacctctg acttgagcgt cgatttttgt gatgctcgtc aggggggcgg 3180
agcctatgga aaaacgccag caacgcggcc tttttacggt tcctggcctt ttgctggcct 3240
tttgctcaca tgttctttcc tgcgttatcc cctgattctg tggataaccg tattaccgcc 3300
tttgagtgag ctgataccgc tcgccgcagc cgaacgaccg agcgcagcga gtcagtgagc 3360
gaggaagcgg aagagcgcct gatgcggtat tttctcctta cgcatctgtg cggtatttca 3420
caccgcaatg gtgcactctc agtacaatct gctctgatgc cgcatagtta agccagtata 3480
cactccgcta tcgctacgtg actgggtcat ggctgcgccc cgacacccgc caacacccgc 3540
tgacgcgccc tgacgggctt gtctgctccc ggcatccgct tacagacaag ctgtgaccgt 3600
ctccgggagc tgcatgtgtc agaggttttc accgtcatca ccgaaacgcg cgaggcagct 3660
gcggtaaagc tcatcagcgt ggtcgtgaag cgattcacag atgtctgcct gttcatccgc 3720
gtccagctcg ttgagtttct ccagaagcgt taatgtctgg cttctgataa agcgggccat 3780
gttaagggcg gttttttcct gtttggtcac tgatgcctcc gtgtaagggg gatttctgtt 3840
catgggggta atgataccga tgaaacgaga gaggatgctc acgatacggg ttactgatga 3900
tgaacatgcc cggttactgg aacgttgtga gggtaaacaa ctggcggtat ggatgcggcg 3960
ggaccagaga aaaatcactc agggtcaatg ccagcgcttc gttaatacag atgtaggtgt 4020
tccacagggt agccagcagc atcctgcgat gcagatccgg aacataatgg tgcagggcgc 4080
tgacttccgc gtttccagac tttacgaaac acggaaaccg aagaccattc atgttgttgc 4140
tcaggtcgca gacgttttgc agcagcagtc gcttcacgtt cgctcgcgta tcggtgattc 4200
attctgctaa ccagtaaggc aaccccgcca gcctagccgg gtcctcaacg acaggagcac 4260
gatcatgcgc acccgtggcc aggacccaac gctgcccgag atgcgccgcg tgcggctgct 4320
ggagatggcg gacgcgatgg atatgttctg ccaagggttg gtttgcgcat tcacagttct 4380
ccgcaagaat tgattggctc caattcttgg agtggtgaat ccgttagcga ggtgccgccg 4440
gcttccattc aggtcgaggt ggcccggctc catgcaccgc gacgcaacgc ggggaggcag 4500
acaaggtata gggcggcgcc tacaatccat gccaacccgt tccatgtgct cgccgaggcg 4560
gcataaatcg ccgtgacgat cagcggtcca atgatcgaag ttaggctggt aagagccgcg 4620
agcgatcctt gaagctgtcc ctgatggtcg tcatctacct gcctggacag catggcctgc 4680
aacgcgggca tcccgatgcc gccggaagcg agaagaatca taatggggaa ggccatccag 4740
cctcgcgtcg cgaacgccag caagacgtag cccagcgcgt cggccgccat gccggcgata 4800
atggcctgct tctcgccgaa acgtttggtg gcgggaccag tgacgaaggc ttgagcgagg 4860
gcgtgcaaga ttccgaatac cgcaagcgac aggccgatca tcgtcgcgct ccagcgaaag 4920
cggtcctcgc cgaaaatgac ccagagcgct gccggcacct gtcctacgag ttgcatgata 4980
aagaagacag tcataagtgc ggcgacgata gtcatgcccc gcgcccaccg gaaggagctg 5040
actgggttga aggctctcaa gggcatcggt cgagatcccg gtgcctaatg agtgagctaa 5100
cttacattaa ttgcgttgcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag 5160
ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgccagggt 5220
ggtttttctt ttcaccagtg agacgggcaa cagctgattg cccttcaccg cctggccctg 5280
agagagttgc agcaagcggt ccacgctggt ttgccccagc aggcgaaaat cctgtttgat 5340
ggtggttaac ggcgggatat aacatgagct gtcttcggta tcgtcgtatc ccactaccga 5400
gatatccgca ccaacgcgca gcccggactc ggtaatggcg cgcattgcgc ccagcgccat 5460
ctgatcgttg gcaaccagca tcgcagtggg aacgatgccc tcattcagca tttgcatggt 5520
ttgttgaaaa ccggacatgg cactccagtc gccttcccgt tccgctatcg gctgaatttg 5580
attgcgagtg agatatttat gccagccagc cagacgcaga cgcgccgaga cagaacttaa 5640
tgggcccgct aacagcgcga tttgctggtg acccaatgcg accagatgct ccacgcccag 5700
tcgcgtaccg tcttcatggg agaaaataat actgttgatg ggtgtctggt cagagacatc 5760
aagaaataac gccggaacat tagtgcaggc agcttccaca gcaatggcat cctggtcatc 5820
cagcggatag ttaatgatca gcccactgac gcgttgcgcg agaagattgt gcaccgccgc 5880
tttacaggct tcgacgccgc ttcgttctac catcgacacc accacgctgg cacccagttg 5940
atcggcgcga gatttaatcg ccgcgacaat ttgcgacggc gcgtgcaggg ccagactgga 6000
ggtggcaacg ccaatcagca acgactgttt gcccgccagt tgttgtgcca cgcggttggg 6060
aatgtaattc agctccgcca tcgccgcttc cactttttcc cgcgttttcg cagaaacgtg 6120
gctggcctgg ttcaccacgc gggaaacggt ctgataagag acaccggcat actctgcgac 6180
atcgtataac gttactggtt tcacattcac caccctgaat tgactctctt ccgggcgcta 6240
tcatgccata ccgcgaaagg ttttgcgcca ttcgatggtg tccgggatct cgacgctctc 6300
ccttatgcga ctcctgcatt aggaagcagc ccagtagtag gttgaggccg ttgagcaccg 6360
ccgccgcaag gaatggtgca tgcaaggaga tggcgcccaa cagtcccccg gccacggggc 6420
ctgccaccat acccacgccg aaacaagcgc tcatgagccc gaagtggcga gcccgatctt 6480
ccccatcggt gatgtcggcg atataggcgc cagcaaccgc acctgtggcg ccggtgatgc 6540
cggccacgat gcgtccggcg tagaggatcg a 6571
<210> 98
<211> 6550
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 98
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gtccattatc 120
atggaagtgg ccacaatgca agccaaactg acaaaaaatg agttcattga gtggctgaaa 180
acgtccgagg gtaaacagtt caacgtggac ctgtggtacg gttttcagtg tttcgactac 240
gccaacgctg gctggaaagt gctgttcggc ctgctgctga aaggcctggg agccaaagac 300
atcccttttg caaacaattt cgatggcctg gccacagttt atcaaaacac ccctgacttt 360
ctggcccaac caggcgacat ggtggtgttt ggttctaatt atggcgcagg ctatggccac 420
gtagcctggg tgatcgaagc cacactggac tacattattg tttatgagca aaactggctg 480
ggaggcggat ggacagacgg catcgaacag cctggctggg gctgggagaa agtgacacgc 540
cgtcaacatg cctatgactt ccctatgtgg ttcatccgtc ctaatttcaa aggtggtaaa 600
ctggaagtta gcaaagcagc aaccattaaa cagtccgatg ttaaacaaga agtgaaaaaa 660
caagaggcca aacaaattgt gaaagccacc gattggaaac agaacaaaga tggcatttgg 720
tataaagcag aacatgccag ctttaccgtt accgcaccgg aaggcattat tacccgttat 780
aaaggtccgt ggaccggtca tccgcaggca ggcgtactgc agaaaggtca gaccattaaa 840
tacgatgaag tgcagaaatt tgatggccat gtttgggtta gctgggaaac ctttgaaggt 900
gaaaccgttt atatgccggt tcgtacctgg gatgcaaaaa ccggtaaagt gggcaaactg 960
tggggtgaaa tcaaagagct ccgtcgtcgt cgccgtcggc gtcgtcgtta aggatccggc 1020
tgctaacaaa gcccgaaagg aagctgagtt ggctgctgcc accgctgagc aataactagc 1080
ataacccctt ggggcctcta aacgggtctt gaggggtttt ttgctgaaag gaggaactat 1140
atccggatat cccgcaagag gcccggcagt accggcataa ccaagcctat gcctacagca 1200
tccagggtga cggtgccgag gatgacgatg agcgcattgt tagatttcat acacggtgcc 1260
tgactgcgtt agcaatttaa ctgtgataaa ctaccgcatt aaagctagct tatcgatgat 1320
aagctgtcaa acatgagaat taattcttga agacgaaagg gcctcgtgat acgcctattt 1380
ttataggtta atgtcatgat aataatggtt tcttagacgt caggtggcac ttttcgggga 1440
aatgtgcgcg gaacccctat ttgtttattt ttctaaatac attcaaatat gtatccgctc 1500
atgagacaat aaccctgata aatgcttcaa taatattgaa aaaggaagag tatgagtatt 1560
caacatttcc gtgtcgccct tattcccttt tttgcggcat tttgccttcc tgtttttgct 1620
cacccagaaa cgctggtgaa agtaaaagat gctgaagatc agttgggtgc acgagtgggt 1680
tacatcgaac tggatctcaa cagcggtaag atccttgaga gttttcgccc cgaagaacgt 1740
tttccaatga tgagcacttt taaagttctg ctatgtggcg cggtattatc ccgtgttgac 1800
gccgggcaag agcaactcgg tcgccgcata cactattctc agaatgactt ggttgagtac 1860
tcaccagtca cagaaaagca tcttacggat ggcatgacag taagagaatt atgcagtgct 1920
gccataacca tgagtgataa cactgcggcc aacttacttc tgacaacgat cggaggaccg 1980
aaggagctaa ccgctttttt gcacaacatg ggggatcatg taactcgcct tgatcgttgg 2040
gaaccggagc tgaatgaagc cataccaaac gacgagcgtg acaccacgat gcctgcagca 2100
atggcaacaa cgttgcgcaa actattaact ggcgaactac ttactctagc ttcccggcaa 2160
caattaatag actggatgga ggcggataaa gttgcaggac cacttctgcg ctcggccctt 2220
ccggctggct ggtttattgc tgataaatct ggagccggtg agcgtgggtc tcgcggtatc 2280
attgcagcac tggggccaga tggtaagccc tcccgtatcg tagttatcta cacgacgggg 2340
agtcaggcaa ctatggatga acgaaataga cagatcgctg agataggtgc ctcactgatt 2400
aagcattggt aactgtcaga ccaagtttac tcatatatac tttagattga tttaaaactt 2460
catttttaat ttaaaaggat ctaggtgaag atcctttttg ataatctcat gaccaaaatc 2520
ccttaacgtg agttttcgtt ccactgagcg tcagaccccg tagaaaagat caaaggatct 2580
tcttgagatc ctttttttct gcgcgtaatc tgctgcttgc aaacaaaaaa accaccgcta 2640
ccagcggtgg tttgtttgcc ggatcaagag ctaccaactc tttttccgaa ggtaactggc 2700
ttcagcagag cgcagatacc aaatactgtc cttctagtgt agccgtagtt aggccaccac 2760
ttcaagaact ctgtagcacc gcctacatac ctcgctctgc taatcctgtt accagtggct 2820
gctgccagtg gcgataagtc gtgtcttacc gggttggact caagacgata gttaccggat 2880
aaggcgcagc ggtcgggctg aacggggggt tcgtgcacac agcccagctt ggagcgaacg 2940
acctacaccg aactgagata cctacagcgt gagctatgag aaagcgccac gcttcccgaa 3000
gggagaaagg cggacaggta tccggtaagc ggcagggtcg gaacaggaga gcgcacgagg 3060
gagcttccag ggggaaacgc ctggtatctt tatagtcctg tcgggtttcg ccacctctga 3120
cttgagcgtc gatttttgtg atgctcgtca ggggggcgga gcctatggaa aaacgccagc 3180
aacgcggcct ttttacggtt cctggccttt tgctggcctt ttgctcacat gttctttcct 3240
gcgttatccc ctgattctgt ggataaccgt attaccgcct ttgagtgagc tgataccgct 3300
cgccgcagcc gaacgaccga gcgcagcgag tcagtgagcg aggaagcgga agagcgcctg 3360
atgcggtatt ttctccttac gcatctgtgc ggtatttcac accgcaatgg tgcactctca 3420
gtacaatctg ctctgatgcc gcatagttaa gccagtatac actccgctat cgctacgtga 3480
ctgggtcatg gctgcgcccc gacacccgcc aacacccgct gacgcgccct gacgggcttg 3540
tctgctcccg gcatccgctt acagacaagc tgtgaccgtc tccgggagct gcatgtgtca 3600
gaggttttca ccgtcatcac cgaaacgcgc gaggcagctg cggtaaagct catcagcgtg 3660
gtcgtgaagc gattcacaga tgtctgcctg ttcatccgcg tccagctcgt tgagtttctc 3720
cagaagcgtt aatgtctggc ttctgataaa gcgggccatg ttaagggcgg ttttttcctg 3780
tttggtcact gatgcctccg tgtaaggggg atttctgttc atgggggtaa tgataccgat 3840
gaaacgagag aggatgctca cgatacgggt tactgatgat gaacatgccc ggttactgga 3900
acgttgtgag ggtaaacaac tggcggtatg gatgcggcgg gaccagagaa aaatcactca 3960
gggtcaatgc cagcgcttcg ttaatacaga tgtaggtgtt ccacagggta gccagcagca 4020
tcctgcgatg cagatccgga acataatggt gcagggcgct gacttccgcg tttccagact 4080
ttacgaaaca cggaaaccga agaccattca tgttgttgct caggtcgcag acgttttgca 4140
gcagcagtcg cttcacgttc gctcgcgtat cggtgattca ttctgctaac cagtaaggca 4200
accccgccag cctagccggg tcctcaacga caggagcacg atcatgcgca cccgtggcca 4260
ggacccaacg ctgcccgaga tgcgccgcgt gcggctgctg gagatggcgg acgcgatgga 4320
tatgttctgc caagggttgg tttgcgcatt cacagttctc cgcaagaatt gattggctcc 4380
aattcttgga gtggtgaatc cgttagcgag gtgccgccgg cttccattca ggtcgaggtg 4440
gcccggctcc atgcaccgcg acgcaacgcg gggaggcaga caaggtatag ggcggcgcct 4500
acaatccatg ccaacccgtt ccatgtgctc gccgaggcgg cataaatcgc cgtgacgatc 4560
agcggtccaa tgatcgaagt taggctggta agagccgcga gcgatccttg aagctgtccc 4620
tgatggtcgt catctacctg cctggacagc atggcctgca acgcgggcat cccgatgccg 4680
ccggaagcga gaagaatcat aatggggaag gccatccagc ctcgcgtcgc gaacgccagc 4740
aagacgtagc ccagcgcgtc ggccgccatg ccggcgataa tggcctgctt ctcgccgaaa 4800
cgtttggtgg cgggaccagt gacgaaggct tgagcgaggg cgtgcaagat tccgaatacc 4860
gcaagcgaca ggccgatcat cgtcgcgctc cagcgaaagc ggtcctcgcc gaaaatgacc 4920
cagagcgctg ccggcacctg tcctacgagt tgcatgataa agaagacagt cataagtgcg 4980
gcgacgatag tcatgccccg cgcccaccgg aaggagctga ctgggttgaa ggctctcaag 5040
ggcatcggtc gagatcccgg tgcctaatga gtgagctaac ttacattaat tgcgttgcgc 5100
tcactgcccg ctttccagtc gggaaacctg tcgtgccagc tgcattaatg aatcggccaa 5160
cgcgcgggga gaggcggttt gcgtattggg cgccagggtg gtttttcttt tcaccagtga 5220
gacgggcaac agctgattgc ccttcaccgc ctggccctga gagagttgca gcaagcggtc 5280
cacgctggtt tgccccagca ggcgaaaatc ctgtttgatg gtggttaacg gcgggatata 5340
acatgagctg tcttcggtat cgtcgtatcc cactaccgag atatccgcac caacgcgcag 5400
cccggactcg gtaatggcgc gcattgcgcc cagcgccatc tgatcgttgg caaccagcat 5460
cgcagtggga acgatgccct cattcagcat ttgcatggtt tgttgaaaac cggacatggc 5520
actccagtcg ccttcccgtt ccgctatcgg ctgaatttga ttgcgagtga gatatttatg 5580
ccagccagcc agacgcagac gcgccgagac agaacttaat gggcccgcta acagcgcgat 5640
ttgctggtga cccaatgcga ccagatgctc cacgcccagt cgcgtaccgt cttcatggga 5700
gaaaataata ctgttgatgg gtgtctggtc agagacatca agaaataacg ccggaacatt 5760
agtgcaggca gcttccacag caatggcatc ctggtcatcc agcggatagt taatgatcag 5820
cccactgacg cgttgcgcga gaagattgtg caccgccgct ttacaggctt cgacgccgct 5880
tcgttctacc atcgacacca ccacgctggc acccagttga tcggcgcgag atttaatcgc 5940
cgcgacaatt tgcgacggcg cgtgcagggc cagactggag gtggcaacgc caatcagcaa 6000
cgactgtttg cccgccagtt gttgtgccac gcggttggga atgtaattca gctccgccat 6060
cgccgcttcc actttttccc gcgttttcgc agaaacgtgg ctggcctggt tcaccacgcg 6120
ggaaacggtc tgataagaga caccggcata ctctgcgaca tcgtataacg ttactggttt 6180
cacattcacc accctgaatt gactctcttc cgggcgctat catgccatac cgcgaaaggt 6240
tttgcgccat tcgatggtgt ccgggatctc gacgctctcc cttatgcgac tcctgcatta 6300
ggaagcagcc cagtagtagg ttgaggccgt tgagcaccgc cgccgcaagg aatggtgcat 6360
gcaaggagat ggcgcccaac agtcccccgg ccacggggcc tgccaccata cccacgccga 6420
aacaagcgct catgagcccg aagtggcgag cccgatcttc cccatcggtg atgtcggcga 6480
tataggcgcc agcaaccgca cctgtggcgc cggtgatgcc ggccacgatg cgtccggcgt 6540
agaggatcga 6550
<210> 99
<211> 6562
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 99
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gtccattatc 120
atggaagtgg ccacaatgca agccaaactg acaaaaaatg agttcattga gtggctgaaa 180
acgtccgagg gtaaacagtt caacgtggac ctgtggtacg gttttcagtg tttcgactac 240
gccaacgctg gctggaaagt gctgttcggc ctgctgctga aaggcctggg agccaaagac 300
atcccttttg caaacaattt cgatggcctg gccacagttt atcaaaacac ccctgacttt 360
ctggcccaac caggcgacat ggtggtgttt ggttctaatt atggcgcagg ctatggccac 420
gtagcctggg tgatcgaagc cacactggac tacattattg tttatgagca aaactggctg 480
ggaggcggat ggacagacgg catcgaacag cctggctggg gctgggagaa agtgacacgc 540
cgtcaacatg cctatgactt ccctatgtgg ttcatccgtc ctaatttcaa aggtggtaaa 600
ctggaagtta gcaaagcagc aaccattaaa cagtccgatg ttaaacaaga agtgaaaaaa 660
caagaggcca aacaaattgt gaaagccacc gattggaaac agaacaaaga tggcatttgg 720
tataaagcag aacatgccag ctttaccgtt accgcaccgg aaggcattat tacccgttat 780
aaaggtccgt ggaccggtca tccgcaggca ggcgtactgc agaaaggtca gaccattaaa 840
tacgatgaag tgcagaaatt tgatggccat gtttgggtta gctgggaaac ctttgaaggt 900
gaaaccgttt atatgccggt tcgtacctgg gatgcaaaaa ccggtaaagt gggcaaactg 960
tggggtgaaa tcaaagagct cggtcgtaaa aaacgtcgtc agcgtcgtcg tccgcctcag 1020
taaggatccg gctgctaaca aagcccgaaa ggaagctgag ttggctgctg ccaccgctga 1080
gcaataacta gcataacccc ttggggcctc taaacgggtc ttgaggggtt ttttgctgaa 1140
aggaggaact atatccggat atcccgcaag aggcccggca gtaccggcat aaccaagcct 1200
atgcctacag catccagggt gacggtgccg aggatgacga tgagcgcatt gttagatttc 1260
atacacggtg cctgactgcg ttagcaattt aactgtgata aactaccgca ttaaagctag 1320
cttatcgatg ataagctgtc aaacatgaga attaattctt gaagacgaaa gggcctcgtg 1380
atacgcctat ttttataggt taatgtcatg ataataatgg tttcttagac gtcaggtggc 1440
acttttcggg gaaatgtgcg cggaacccct atttgtttat ttttctaaat acattcaaat 1500
atgtatccgc tcatgagaca ataaccctga taaatgcttc aataatattg aaaaaggaag 1560
agtatgagta ttcaacattt ccgtgtcgcc cttattccct tttttgcggc attttgcctt 1620
cctgtttttg ctcacccaga aacgctggtg aaagtaaaag atgctgaaga tcagttgggt 1680
gcacgagtgg gttacatcga actggatctc aacagcggta agatccttga gagttttcgc 1740
cccgaagaac gttttccaat gatgagcact tttaaagttc tgctatgtgg cgcggtatta 1800
tcccgtgttg acgccgggca agagcaactc ggtcgccgca tacactattc tcagaatgac 1860
ttggttgagt actcaccagt cacagaaaag catcttacgg atggcatgac agtaagagaa 1920
ttatgcagtg ctgccataac catgagtgat aacactgcgg ccaacttact tctgacaacg 1980
atcggaggac cgaaggagct aaccgctttt ttgcacaaca tgggggatca tgtaactcgc 2040
cttgatcgtt gggaaccgga gctgaatgaa gccataccaa acgacgagcg tgacaccacg 2100
atgcctgcag caatggcaac aacgttgcgc aaactattaa ctggcgaact acttactcta 2160
gcttcccggc aacaattaat agactggatg gaggcggata aagttgcagg accacttctg 2220
cgctcggccc ttccggctgg ctggtttatt gctgataaat ctggagccgg tgagcgtggg 2280
tctcgcggta tcattgcagc actggggcca gatggtaagc cctcccgtat cgtagttatc 2340
tacacgacgg ggagtcaggc aactatggat gaacgaaata gacagatcgc tgagataggt 2400
gcctcactga ttaagcattg gtaactgtca gaccaagttt actcatatat actttagatt 2460
gatttaaaac ttcattttta atttaaaagg atctaggtga agatcctttt tgataatctc 2520
atgaccaaaa tcccttaacg tgagttttcg ttccactgag cgtcagaccc cgtagaaaag 2580
atcaaaggat cttcttgaga tccttttttt ctgcgcgtaa tctgctgctt gcaaacaaaa 2640
aaaccaccgc taccagcggt ggtttgtttg ccggatcaag agctaccaac tctttttccg 2700
aaggtaactg gcttcagcag agcgcagata ccaaatactg tccttctagt gtagccgtag 2760
ttaggccacc acttcaagaa ctctgtagca ccgcctacat acctcgctct gctaatcctg 2820
ttaccagtgg ctgctgccag tggcgataag tcgtgtctta ccgggttgga ctcaagacga 2880
tagttaccgg ataaggcgca gcggtcgggc tgaacggggg gttcgtgcac acagcccagc 2940
ttggagcgaa cgacctacac cgaactgaga tacctacagc gtgagctatg agaaagcgcc 3000
acgcttcccg aagggagaaa ggcggacagg tatccggtaa gcggcagggt cggaacagga 3060
gagcgcacga gggagcttcc agggggaaac gcctggtatc tttatagtcc tgtcgggttt 3120
cgccacctct gacttgagcg tcgatttttg tgatgctcgt caggggggcg gagcctatgg 3180
aaaaacgcca gcaacgcggc ctttttacgg ttcctggcct tttgctggcc ttttgctcac 3240
atgttctttc ctgcgttatc ccctgattct gtggataacc gtattaccgc ctttgagtga 3300
gctgataccg ctcgccgcag ccgaacgacc gagcgcagcg agtcagtgag cgaggaagcg 3360
gaagagcgcc tgatgcggta ttttctcctt acgcatctgt gcggtatttc acaccgcaat 3420
ggtgcactct cagtacaatc tgctctgatg ccgcatagtt aagccagtat acactccgct 3480
atcgctacgt gactgggtca tggctgcgcc ccgacacccg ccaacacccg ctgacgcgcc 3540
ctgacgggct tgtctgctcc cggcatccgc ttacagacaa gctgtgaccg tctccgggag 3600
ctgcatgtgt cagaggtttt caccgtcatc accgaaacgc gcgaggcagc tgcggtaaag 3660
ctcatcagcg tggtcgtgaa gcgattcaca gatgtctgcc tgttcatccg cgtccagctc 3720
gttgagtttc tccagaagcg ttaatgtctg gcttctgata aagcgggcca tgttaagggc 3780
ggttttttcc tgtttggtca ctgatgcctc cgtgtaaggg ggatttctgt tcatgggggt 3840
aatgataccg atgaaacgag agaggatgct cacgatacgg gttactgatg atgaacatgc 3900
ccggttactg gaacgttgtg agggtaaaca actggcggta tggatgcggc gggaccagag 3960
aaaaatcact cagggtcaat gccagcgctt cgttaataca gatgtaggtg ttccacaggg 4020
tagccagcag catcctgcga tgcagatccg gaacataatg gtgcagggcg ctgacttccg 4080
cgtttccaga ctttacgaaa cacggaaacc gaagaccatt catgttgttg ctcaggtcgc 4140
agacgttttg cagcagcagt cgcttcacgt tcgctcgcgt atcggtgatt cattctgcta 4200
accagtaagg caaccccgcc agcctagccg ggtcctcaac gacaggagca cgatcatgcg 4260
cacccgtggc caggacccaa cgctgcccga gatgcgccgc gtgcggctgc tggagatggc 4320
ggacgcgatg gatatgttct gccaagggtt ggtttgcgca ttcacagttc tccgcaagaa 4380
ttgattggct ccaattcttg gagtggtgaa tccgttagcg aggtgccgcc ggcttccatt 4440
caggtcgagg tggcccggct ccatgcaccg cgacgcaacg cggggaggca gacaaggtat 4500
agggcggcgc ctacaatcca tgccaacccg ttccatgtgc tcgccgaggc ggcataaatc 4560
gccgtgacga tcagcggtcc aatgatcgaa gttaggctgg taagagccgc gagcgatcct 4620
tgaagctgtc cctgatggtc gtcatctacc tgcctggaca gcatggcctg caacgcgggc 4680
atcccgatgc cgccggaagc gagaagaatc ataatgggga aggccatcca gcctcgcgtc 4740
gcgaacgcca gcaagacgta gcccagcgcg tcggccgcca tgccggcgat aatggcctgc 4800
ttctcgccga aacgtttggt ggcgggacca gtgacgaagg cttgagcgag ggcgtgcaag 4860
attccgaata ccgcaagcga caggccgatc atcgtcgcgc tccagcgaaa gcggtcctcg 4920
ccgaaaatga cccagagcgc tgccggcacc tgtcctacga gttgcatgat aaagaagaca 4980
gtcataagtg cggcgacgat agtcatgccc cgcgcccacc ggaaggagct gactgggttg 5040
aaggctctca agggcatcgg tcgagatccc ggtgcctaat gagtgagcta acttacatta 5100
attgcgttgc gctcactgcc cgctttccag tcgggaaacc tgtcgtgcca gctgcattaa 5160
tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg ggcgccaggg tggtttttct 5220
tttcaccagt gagacgggca acagctgatt gcccttcacc gcctggccct gagagagttg 5280
cagcaagcgg tccacgctgg tttgccccag caggcgaaaa tcctgtttga tggtggttaa 5340
cggcgggata taacatgagc tgtcttcggt atcgtcgtat cccactaccg agatatccgc 5400
accaacgcgc agcccggact cggtaatggc gcgcattgcg cccagcgcca tctgatcgtt 5460
ggcaaccagc atcgcagtgg gaacgatgcc ctcattcagc atttgcatgg tttgttgaaa 5520
accggacatg gcactccagt cgccttcccg ttccgctatc ggctgaattt gattgcgagt 5580
gagatattta tgccagccag ccagacgcag acgcgccgag acagaactta atgggcccgc 5640
taacagcgcg atttgctggt gacccaatgc gaccagatgc tccacgccca gtcgcgtacc 5700
gtcttcatgg gagaaaataa tactgttgat gggtgtctgg tcagagacat caagaaataa 5760
cgccggaaca ttagtgcagg cagcttccac agcaatggca tcctggtcat ccagcggata 5820
gttaatgatc agcccactga cgcgttgcgc gagaagattg tgcaccgccg ctttacaggc 5880
ttcgacgccg cttcgttcta ccatcgacac caccacgctg gcacccagtt gatcggcgcg 5940
agatttaatc gccgcgacaa tttgcgacgg cgcgtgcagg gccagactgg aggtggcaac 6000
gccaatcagc aacgactgtt tgcccgccag ttgttgtgcc acgcggttgg gaatgtaatt 6060
cagctccgcc atcgccgctt ccactttttc ccgcgttttc gcagaaacgt ggctggcctg 6120
gttcaccacg cgggaaacgg tctgataaga gacaccggca tactctgcga catcgtataa 6180
cgttactggt ttcacattca ccaccctgaa ttgactctct tccgggcgct atcatgccat 6240
accgcgaaag gttttgcgcc attcgatggt gtccgggatc tcgacgctct cccttatgcg 6300
actcctgcat taggaagcag cccagtagta ggttgaggcc gttgagcacc gccgccgcaa 6360
ggaatggtgc atgcaaggag atggcgccca acagtccccc ggccacgggg cctgccacca 6420
tacccacgcc gaaacaagcg ctcatgagcc cgaagtggcg agcccgatct tccccatcgg 6480
tgatgtcggc gatataggcg ccagcaaccg cacctgtggc gccggtgatg ccggccacga 6540
tgcgtccggc gtagaggatc ga 6562
<210> 100
<211> 6187
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 100
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gtccattatc 120
atggaagtgg ccacaatgca agccaaactg acaaaaaatg agttcattga gtggctgaaa 180
acgtccgagg gtaaacagtt caacgtggac ctgtggtacg gttttcagtg tttcgactac 240
gccaacgctg gctggaaagt gctgttcggc ctgctgctga aaggcctggg agccaaagac 300
atcccttttg caaacaattt cgatggcctg gccacagttt atcaaaacac ccctgacttt 360
ctggcccaac caggcgacat ggtggtgttt ggttctaatt atggcgcagg ctatggccac 420
gtagcctggg tgatcgaagc cacactggac tacattattg tttatgagca aaactggctg 480
ggaggcggat ggacagacgg catcgaacag cctggctggg gctgggagaa agtgacacgc 540
cgtcaacatg cctatgactt ccctatgtgg ttcatccgtc ctaatttcaa agagctccgc 600
cagatcaaaa tttggtttca gaatcgtcgc atgaaatgga aaaaataagg atccggctgc 660
taacaaagcc cgaaaggaag ctgagttggc tgctgccacc gctgagcaat aactagcata 720
accccttggg gcctctaaac gggtcttgag gggttttttg ctgaaaggag gaactatatc 780
cggatatccc gcaagaggcc cggcagtacc ggcataacca agcctatgcc tacagcatcc 840
agggtgacgg tgccgaggat gacgatgagc gcattgttag atttcataca cggtgcctga 900
ctgcgttagc aatttaactg tgataaacta ccgcattaaa gctagcttat cgatgataag 960
ctgtcaaaca tgagaattaa ttcttgaaga cgaaagggcc tcgtgatacg cctattttta 1020
taggttaatg tcatgataat aatggtttct tagacgtcag gtggcacttt tcggggaaat 1080
gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta tccgctcatg 1140
agacaataac cctgataaat gcttcaataa tattgaaaaa ggaagagtat gagtattcaa 1200
catttccgtg tcgcccttat tccctttttt gcggcatttt gccttcctgt ttttgctcac 1260
ccagaaacgc tggtgaaagt aaaagatgct gaagatcagt tgggtgcacg agtgggttac 1320
atcgaactgg atctcaacag cggtaagatc cttgagagtt ttcgccccga agaacgtttt 1380
ccaatgatga gcacttttaa agttctgcta tgtggcgcgg tattatcccg tgttgacgcc 1440
gggcaagagc aactcggtcg ccgcatacac tattctcaga atgacttggt tgagtactca 1500
ccagtcacag aaaagcatct tacggatggc atgacagtaa gagaattatg cagtgctgcc 1560
ataaccatga gtgataacac tgcggccaac ttacttctga caacgatcgg aggaccgaag 1620
gagctaaccg cttttttgca caacatgggg gatcatgtaa ctcgccttga tcgttgggaa 1680
ccggagctga atgaagccat accaaacgac gagcgtgaca ccacgatgcc tgcagcaatg 1740
gcaacaacgt tgcgcaaact attaactggc gaactactta ctctagcttc ccggcaacaa 1800
ttaatagact ggatggaggc ggataaagtt gcaggaccac ttctgcgctc ggcccttccg 1860
gctggctggt ttattgctga taaatctgga gccggtgagc gtgggtctcg cggtatcatt 1920
gcagcactgg ggccagatgg taagccctcc cgtatcgtag ttatctacac gacggggagt 1980
caggcaacta tggatgaacg aaatagacag atcgctgaga taggtgcctc actgattaag 2040
cattggtaac tgtcagacca agtttactca tatatacttt agattgattt aaaacttcat 2100
ttttaattta aaaggatcta ggtgaagatc ctttttgata atctcatgac caaaatccct 2160
taacgtgagt tttcgttcca ctgagcgtca gaccccgtag aaaagatcaa aggatcttct 2220
tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa caaaaaaacc accgctacca 2280
gcggtggttt gtttgccgga tcaagagcta ccaactcttt ttccgaaggt aactggcttc 2340
agcagagcgc agataccaaa tactgtcctt ctagtgtagc cgtagttagg ccaccacttc 2400
aagaactctg tagcaccgcc tacatacctc gctctgctaa tcctgttacc agtggctgct 2460
gccagtggcg ataagtcgtg tcttaccggg ttggactcaa gacgatagtt accggataag 2520
gcgcagcggt cgggctgaac ggggggttcg tgcacacagc ccagcttgga gcgaacgacc 2580
tacaccgaac tgagatacct acagcgtgag ctatgagaaa gcgccacgct tcccgaaggg 2640
agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa caggagagcg cacgagggag 2700
cttccagggg gaaacgcctg gtatctttat agtcctgtcg ggtttcgcca cctctgactt 2760
gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc tatggaaaaa cgccagcaac 2820
gcggcctttt tacggttcct ggccttttgc tggccttttg ctcacatgtt ctttcctgcg 2880
ttatcccctg attctgtgga taaccgtatt accgcctttg agtgagctga taccgctcgc 2940
cgcagccgaa cgaccgagcg cagcgagtca gtgagcgagg aagcggaaga gcgcctgatg 3000
cggtattttc tccttacgca tctgtgcggt atttcacacc gcaatggtgc actctcagta 3060
caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 3120
ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 3180
gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 3240
gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 3300
gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 3360
aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 3420
ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 3480
acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 3540
ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 3600
tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 3660
tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3720
cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3780
gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3840
ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgcgcaccc gtggccagga 3900
cccaacgctg cccgagatgc gccgcgtgcg gctgctggag atggcggacg cgatggatat 3960
gttctgccaa gggttggttt gcgcattcac agttctccgc aagaattgat tggctccaat 4020
tcttggagtg gtgaatccgt tagcgaggtg ccgccggctt ccattcaggt cgaggtggcc 4080
cggctccatg caccgcgacg caacgcgggg aggcagacaa ggtatagggc ggcgcctaca 4140
atccatgcca acccgttcca tgtgctcgcc gaggcggcat aaatcgccgt gacgatcagc 4200
ggtccaatga tcgaagttag gctggtaaga gccgcgagcg atccttgaag ctgtccctga 4260
tggtcgtcat ctacctgcct ggacagcatg gcctgcaacg cgggcatccc gatgccgccg 4320
gaagcgagaa gaatcataat ggggaaggcc atccagcctc gcgtcgcgaa cgccagcaag 4380
acgtagccca gcgcgtcggc cgccatgccg gcgataatgg cctgcttctc gccgaaacgt 4440
ttggtggcgg gaccagtgac gaaggcttga gcgagggcgt gcaagattcc gaataccgca 4500
agcgacaggc cgatcatcgt cgcgctccag cgaaagcggt cctcgccgaa aatgacccag 4560
agcgctgccg gcacctgtcc tacgagttgc atgataaaga agacagtcat aagtgcggcg 4620
acgatagtca tgccccgcgc ccaccggaag gagctgactg ggttgaaggc tctcaagggc 4680
atcggtcgag atcccggtgc ctaatgagtg agctaactta cattaattgc gttgcgctca 4740
ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc 4800
gcggggagag gcggtttgcg tattgggcgc cagggtggtt tttcttttca ccagtgagac 4860
gggcaacagc tgattgccct tcaccgcctg gccctgagag agttgcagca agcggtccac 4920
gctggtttgc cccagcaggc gaaaatcctg tttgatggtg gttaacggcg ggatataaca 4980
tgagctgtct tcggtatcgt cgtatcccac taccgagata tccgcaccaa cgcgcagccc 5040
ggactcggta atggcgcgca ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc 5100
agtgggaacg atgccctcat tcagcatttg catggtttgt tgaaaaccgg acatggcact 5160
ccagtcgcct tcccgttccg ctatcggctg aatttgattg cgagtgagat atttatgcca 5220
gccagccaga cgcagacgcg ccgagacaga acttaatggg cccgctaaca gcgcgatttg 5280
ctggtgaccc aatgcgacca gatgctccac gcccagtcgc gtaccgtctt catgggagaa 5340
aataatactg ttgatgggtg tctggtcaga gacatcaaga aataacgccg gaacattagt 5400
gcaggcagct tccacagcaa tggcatcctg gtcatccagc ggatagttaa tgatcagccc 5460
actgacgcgt tgcgcgagaa gattgtgcac cgccgcttta caggcttcga cgccgcttcg 5520
ttctaccatc gacaccacca cgctggcacc cagttgatcg gcgcgagatt taatcgccgc 5580
gacaatttgc gacggcgcgt gcagggccag actggaggtg gcaacgccaa tcagcaacga 5640
ctgtttgccc gccagttgtt gtgccacgcg gttgggaatg taattcagct ccgccatcgc 5700
cgcttccact ttttcccgcg ttttcgcaga aacgtggctg gcctggttca ccacgcggga 5760
aacggtctga taagagacac cggcatactc tgcgacatcg tataacgtta ctggtttcac 5820
attcaccacc ctgaattgac tctcttccgg gcgctatcat gccataccgc gaaaggtttt 5880
gcgccattcg atggtgtccg ggatctcgac gctctccctt atgcgactcc tgcattagga 5940
agcagcccag tagtaggttg aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca 6000
aggagatggc gcccaacagt cccccggcca cggggcctgc caccataccc acgccgaaac 6060
aagcgctcat gagcccgaag tggcgagccc gatcttcccc atcggtgatg tcggcgatat 6120
aggcgccagc aaccgcacct gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga 6180
ggatcga 6187
<210> 101
<211> 6166
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 101
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gtccattatc 120
atggaagtgg ccacaatgca agccaaactg acaaaaaatg agttcattga gtggctgaaa 180
acgtccgagg gtaaacagtt caacgtggac ctgtggtacg gttttcagtg tttcgactac 240
gccaacgctg gctggaaagt gctgttcggc ctgctgctga aaggcctggg agccaaagac 300
atcccttttg caaacaattt cgatggcctg gccacagttt atcaaaacac ccctgacttt 360
ctggcccaac caggcgacat ggtggtgttt ggttctaatt atggcgcagg ctatggccac 420
gtagcctggg tgatcgaagc cacactggac tacattattg tttatgagca aaactggctg 480
ggaggcggat ggacagacgg catcgaacag cctggctggg gctgggagaa agtgacacgc 540
cgtcaacatg cctatgactt ccctatgtgg ttcatccgtc ctaatttcaa agagctccgt 600
cgtcgtcgcc gtcggcgtcg tcgttaagga tccggctgct aacaaagccc gaaaggaagc 660
tgagttggct gctgccaccg ctgagcaata actagcataa ccccttgggg cctctaaacg 720
ggtcttgagg ggttttttgc tgaaaggagg aactatatcc ggatatcccg caagaggccc 780
ggcagtaccg gcataaccaa gcctatgcct acagcatcca gggtgacggt gccgaggatg 840
acgatgagcg cattgttaga tttcatacac ggtgcctgac tgcgttagca atttaactgt 900
gataaactac cgcattaaag ctagcttatc gatgataagc tgtcaaacat gagaattaat 960
tcttgaagac gaaagggcct cgtgatacgc ctatttttat aggttaatgt catgataata 1020
atggtttctt agacgtcagg tggcactttt cggggaaatg tgcgcggaac ccctatttgt 1080
ttatttttct aaatacattc aaatatgtat ccgctcatga gacaataacc ctgataaatg 1140
cttcaataat attgaaaaag gaagagtatg agtattcaac atttccgtgt cgcccttatt 1200
cccttttttg cggcattttg ccttcctgtt tttgctcacc cagaaacgct ggtgaaagta 1260
aaagatgctg aagatcagtt gggtgcacga gtgggttaca tcgaactgga tctcaacagc 1320
ggtaagatcc ttgagagttt tcgccccgaa gaacgttttc caatgatgag cacttttaaa 1380
gttctgctat gtggcgcggt attatcccgt gttgacgccg ggcaagagca actcggtcgc 1440
cgcatacact attctcagaa tgacttggtt gagtactcac cagtcacaga aaagcatctt 1500
acggatggca tgacagtaag agaattatgc agtgctgcca taaccatgag tgataacact 1560
gcggccaact tacttctgac aacgatcgga ggaccgaagg agctaaccgc ttttttgcac 1620
aacatggggg atcatgtaac tcgccttgat cgttgggaac cggagctgaa tgaagccata 1680
ccaaacgacg agcgtgacac cacgatgcct gcagcaatgg caacaacgtt gcgcaaacta 1740
ttaactggcg aactacttac tctagcttcc cggcaacaat taatagactg gatggaggcg 1800
gataaagttg caggaccact tctgcgctcg gcccttccgg ctggctggtt tattgctgat 1860
aaatctggag ccggtgagcg tgggtctcgc ggtatcattg cagcactggg gccagatggt 1920
aagccctccc gtatcgtagt tatctacacg acggggagtc aggcaactat ggatgaacga 1980
aatagacaga tcgctgagat aggtgcctca ctgattaagc attggtaact gtcagaccaa 2040
gtttactcat atatacttta gattgattta aaacttcatt tttaatttaa aaggatctag 2100
gtgaagatcc tttttgataa tctcatgacc aaaatccctt aacgtgagtt ttcgttccac 2160
tgagcgtcag accccgtaga aaagatcaaa ggatcttctt gagatccttt ttttctgcgc 2220
gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag cggtggtttg tttgccggat 2280
caagagctac caactctttt tccgaaggta actggcttca gcagagcgca gataccaaat 2340
actgtccttc tagtgtagcc gtagttaggc caccacttca agaactctgt agcaccgcct 2400
acatacctcg ctctgctaat cctgttacca gtggctgctg ccagtggcga taagtcgtgt 2460
cttaccgggt tggactcaag acgatagtta ccggataagg cgcagcggtc gggctgaacg 2520
gggggttcgt gcacacagcc cagcttggag cgaacgacct acaccgaact gagataccta 2580
cagcgtgagc tatgagaaag cgccacgctt cccgaaggga gaaaggcgga caggtatccg 2640
gtaagcggca gggtcggaac aggagagcgc acgagggagc ttccaggggg aaacgcctgg 2700
tatctttata gtcctgtcgg gtttcgccac ctctgacttg agcgtcgatt tttgtgatgc 2760
tcgtcagggg ggcggagcct atggaaaaac gccagcaacg cggccttttt acggttcctg 2820
gccttttgct ggccttttgc tcacatgttc tttcctgcgt tatcccctga ttctgtggat 2880
aaccgtatta ccgcctttga gtgagctgat accgctcgcc gcagccgaac gaccgagcgc 2940
agcgagtcag tgagcgagga agcggaagag cgcctgatgc ggtattttct ccttacgcat 3000
ctgtgcggta tttcacaccg caatggtgca ctctcagtac aatctgctct gatgccgcat 3060
agttaagcca gtatacactc cgctatcgct acgtgactgg gtcatggctg cgccccgaca 3120
cccgccaaca cccgctgacg cgccctgacg ggcttgtctg ctcccggcat ccgcttacag 3180
acaagctgtg accgtctccg ggagctgcat gtgtcagagg ttttcaccgt catcaccgaa 3240
acgcgcgagg cagctgcggt aaagctcatc agcgtggtcg tgaagcgatt cacagatgtc 3300
tgcctgttca tccgcgtcca gctcgttgag tttctccaga agcgttaatg tctggcttct 3360
gataaagcgg gccatgttaa gggcggtttt ttcctgtttg gtcactgatg cctccgtgta 3420
agggggattt ctgttcatgg gggtaatgat accgatgaaa cgagagagga tgctcacgat 3480
acgggttact gatgatgaac atgcccggtt actggaacgt tgtgagggta aacaactggc 3540
ggtatggatg cggcgggacc agagaaaaat cactcagggt caatgccagc gcttcgttaa 3600
tacagatgta ggtgttccac agggtagcca gcagcatcct gcgatgcaga tccggaacat 3660
aatggtgcag ggcgctgact tccgcgtttc cagactttac gaaacacgga aaccgaagac 3720
cattcatgtt gttgctcagg tcgcagacgt tttgcagcag cagtcgcttc acgttcgctc 3780
gcgtatcggt gattcattct gctaaccagt aaggcaaccc cgccagccta gccgggtcct 3840
caacgacagg agcacgatca tgcgcacccg tggccaggac ccaacgctgc ccgagatgcg 3900
ccgcgtgcgg ctgctggaga tggcggacgc gatggatatg ttctgccaag ggttggtttg 3960
cgcattcaca gttctccgca agaattgatt ggctccaatt cttggagtgg tgaatccgtt 4020
agcgaggtgc cgccggcttc cattcaggtc gaggtggccc ggctccatgc accgcgacgc 4080
aacgcgggga ggcagacaag gtatagggcg gcgcctacaa tccatgccaa cccgttccat 4140
gtgctcgccg aggcggcata aatcgccgtg acgatcagcg gtccaatgat cgaagttagg 4200
ctggtaagag ccgcgagcga tccttgaagc tgtccctgat ggtcgtcatc tacctgcctg 4260
gacagcatgg cctgcaacgc gggcatcccg atgccgccgg aagcgagaag aatcataatg 4320
gggaaggcca tccagcctcg cgtcgcgaac gccagcaaga cgtagcccag cgcgtcggcc 4380
gccatgccgg cgataatggc ctgcttctcg ccgaaacgtt tggtggcggg accagtgacg 4440
aaggcttgag cgagggcgtg caagattccg aataccgcaa gcgacaggcc gatcatcgtc 4500
gcgctccagc gaaagcggtc ctcgccgaaa atgacccaga gcgctgccgg cacctgtcct 4560
acgagttgca tgataaagaa gacagtcata agtgcggcga cgatagtcat gccccgcgcc 4620
caccggaagg agctgactgg gttgaaggct ctcaagggca tcggtcgaga tcccggtgcc 4680
taatgagtga gctaacttac attaattgcg ttgcgctcac tgcccgcttt ccagtcggga 4740
aacctgtcgt gccagctgca ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt 4800
attgggcgcc agggtggttt ttcttttcac cagtgagacg ggcaacagct gattgccctt 4860
caccgcctgg ccctgagaga gttgcagcaa gcggtccacg ctggtttgcc ccagcaggcg 4920
aaaatcctgt ttgatggtgg ttaacggcgg gatataacat gagctgtctt cggtatcgtc 4980
gtatcccact accgagatat ccgcaccaac gcgcagcccg gactcggtaa tggcgcgcat 5040
tgcgcccagc gccatctgat cgttggcaac cagcatcgca gtgggaacga tgccctcatt 5100
cagcatttgc atggtttgtt gaaaaccgga catggcactc cagtcgcctt cccgttccgc 5160
tatcggctga atttgattgc gagtgagata tttatgccag ccagccagac gcagacgcgc 5220
cgagacagaa cttaatgggc ccgctaacag cgcgatttgc tggtgaccca atgcgaccag 5280
atgctccacg cccagtcgcg taccgtcttc atgggagaaa ataatactgt tgatgggtgt 5340
ctggtcagag acatcaagaa ataacgccgg aacattagtg caggcagctt ccacagcaat 5400
ggcatcctgg tcatccagcg gatagttaat gatcagccca ctgacgcgtt gcgcgagaag 5460
attgtgcacc gccgctttac aggcttcgac gccgcttcgt tctaccatcg acaccaccac 5520
gctggcaccc agttgatcgg cgcgagattt aatcgccgcg acaatttgcg acggcgcgtg 5580
cagggccaga ctggaggtgg caacgccaat cagcaacgac tgtttgcccg ccagttgttg 5640
tgccacgcgg ttgggaatgt aattcagctc cgccatcgcc gcttccactt tttcccgcgt 5700
tttcgcagaa acgtggctgg cctggttcac cacgcgggaa acggtctgat aagagacacc 5760
ggcatactct gcgacatcgt ataacgttac tggtttcaca ttcaccaccc tgaattgact 5820
ctcttccggg cgctatcatg ccataccgcg aaaggttttg cgccattcga tggtgtccgg 5880
gatctcgacg ctctccctta tgcgactcct gcattaggaa gcagcccagt agtaggttga 5940
ggccgttgag caccgccgcc gcaaggaatg gtgcatgcaa ggagatggcg cccaacagtc 6000
ccccggccac ggggcctgcc accataccca cgccgaaaca agcgctcatg agcccgaagt 6060
ggcgagcccg atcttcccca tcggtgatgt cggcgatata ggcgccagca accgcacctg 6120
tggcgccggt gatgccggcc acgatgcgtc cggcgtagag gatcga 6166
<210> 102
<211> 6178
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 102
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat gtccattatc 120
atggaagtgg ccacaatgca agccaaactg acaaaaaatg agttcattga gtggctgaaa 180
acgtccgagg gtaaacagtt caacgtggac ctgtggtacg gttttcagtg tttcgactac 240
gccaacgctg gctggaaagt gctgttcggc ctgctgctga aaggcctggg agccaaagac 300
atcccttttg caaacaattt cgatggcctg gccacagttt atcaaaacac ccctgacttt 360
ctggcccaac caggcgacat ggtggtgttt ggttctaatt atggcgcagg ctatggccac 420
gtagcctggg tgatcgaagc cacactggac tacattattg tttatgagca aaactggctg 480
ggaggcggat ggacagacgg catcgaacag cctggctggg gctgggagaa agtgacacgc 540
cgtcaacatg cctatgactt ccctatgtgg ttcatccgtc ctaatttcaa agagctcggt 600
cgtaaaaaac gtcgtcagcg tcgtcgtccg cctcagtaag gatccggctg ctaacaaagc 660
ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg 720
ggcctctaaa cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggatatcc 780
cgcaagaggc ccggcagtac cggcataacc aagcctatgc ctacagcatc cagggtgacg 840
gtgccgagga tgacgatgag cgcattgtta gatttcatac acggtgcctg actgcgttag 900
caatttaact gtgataaact accgcattaa agctagctta tcgatgataa gctgtcaaac 960
atgagaatta attcttgaag acgaaagggc ctcgtgatac gcctattttt ataggttaat 1020
gtcatgataa taatggtttc ttagacgtca ggtggcactt ttcggggaaa tgtgcgcgga 1080
acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat gagacaataa 1140
ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca acatttccgt 1200
gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca cccagaaacg 1260
ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta catcgaactg 1320
gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt tccaatgatg 1380
agcactttta aagttctgct atgtggcgcg gtattatccc gtgttgacgc cgggcaagag 1440
caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc accagtcaca 1500
gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc cataaccatg 1560
agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa ggagctaacc 1620
gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga accggagctg 1680
aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgcagcaat ggcaacaacg 1740
ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca attaatagac 1800
tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc ggctggctgg 1860
tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat tgcagcactg 1920
gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag tcaggcaact 1980
atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa gcattggtaa 2040
ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca tttttaattt 2100
aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc ttaacgtgag 2160
ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc ttgagatcct 2220
ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt 2280
tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt cagcagagcg 2340
cagataccaa atactgtcct tctagtgtag ccgtagttag gccaccactt caagaactct 2400
gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc tgccagtggc 2460
gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa ggcgcagcgg 2520
tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa 2580
ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg 2640
gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg 2700
ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact tgagcgtcga 2760
tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa cgcggccttt 2820
ttacggttcc tggccttttg ctggcctttt gctcacatgt tctttcctgc gttatcccct 2880
gattctgtgg ataaccgtat taccgccttt gagtgagctg ataccgctcg ccgcagccga 2940
acgaccgagc gcagcgagtc agtgagcgag gaagcggaag agcgcctgat gcggtatttt 3000
ctccttacgc atctgtgcgg tatttcacac cgcaatggtg cactctcagt acaatctgct 3060
ctgatgccgc atagttaagc cagtatacac tccgctatcg ctacgtgact gggtcatggc 3120
tgcgccccga cacccgccaa cacccgctga cgcgccctga cgggcttgtc tgctcccggc 3180
atccgcttac agacaagctg tgaccgtctc cgggagctgc atgtgtcaga ggttttcacc 3240
gtcatcaccg aaacgcgcga ggcagctgcg gtaaagctca tcagcgtggt cgtgaagcga 3300
ttcacagatg tctgcctgtt catccgcgtc cagctcgttg agtttctcca gaagcgttaa 3360
tgtctggctt ctgataaagc gggccatgtt aagggcggtt ttttcctgtt tggtcactga 3420
tgcctccgtg taagggggat ttctgttcat gggggtaatg ataccgatga aacgagagag 3480
gatgctcacg atacgggtta ctgatgatga acatgcccgg ttactggaac gttgtgaggg 3540
taaacaactg gcggtatgga tgcggcggga ccagagaaaa atcactcagg gtcaatgcca 3600
gcgcttcgtt aatacagatg taggtgttcc acagggtagc cagcagcatc ctgcgatgca 3660
gatccggaac ataatggtgc agggcgctga cttccgcgtt tccagacttt acgaaacacg 3720
gaaaccgaag accattcatg ttgttgctca ggtcgcagac gttttgcagc agcagtcgct 3780
tcacgttcgc tcgcgtatcg gtgattcatt ctgctaacca gtaaggcaac cccgccagcc 3840
tagccgggtc ctcaacgaca ggagcacgat catgcgcacc cgtggccagg acccaacgct 3900
gcccgagatg cgccgcgtgc ggctgctgga gatggcggac gcgatggata tgttctgcca 3960
agggttggtt tgcgcattca cagttctccg caagaattga ttggctccaa ttcttggagt 4020
ggtgaatccg ttagcgaggt gccgccggct tccattcagg tcgaggtggc ccggctccat 4080
gcaccgcgac gcaacgcggg gaggcagaca aggtataggg cggcgcctac aatccatgcc 4140
aacccgttcc atgtgctcgc cgaggcggca taaatcgccg tgacgatcag cggtccaatg 4200
atcgaagtta ggctggtaag agccgcgagc gatccttgaa gctgtccctg atggtcgtca 4260
tctacctgcc tggacagcat ggcctgcaac gcgggcatcc cgatgccgcc ggaagcgaga 4320
agaatcataa tggggaaggc catccagcct cgcgtcgcga acgccagcaa gacgtagccc 4380
agcgcgtcgg ccgccatgcc ggcgataatg gcctgcttct cgccgaaacg tttggtggcg 4440
ggaccagtga cgaaggcttg agcgagggcg tgcaagattc cgaataccgc aagcgacagg 4500
ccgatcatcg tcgcgctcca gcgaaagcgg tcctcgccga aaatgaccca gagcgctgcc 4560
ggcacctgtc ctacgagttg catgataaag aagacagtca taagtgcggc gacgatagtc 4620
atgccccgcg cccaccggaa ggagctgact gggttgaagg ctctcaaggg catcggtcga 4680
gatcccggtg cctaatgagt gagctaactt acattaattg cgttgcgctc actgcccgct 4740
ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg cgcggggaga 4800
ggcggtttgc gtattgggcg ccagggtggt ttttcttttc accagtgaga cgggcaacag 4860
ctgattgccc ttcaccgcct ggccctgaga gagttgcagc aagcggtcca cgctggtttg 4920
ccccagcagg cgaaaatcct gtttgatggt ggttaacggc gggatataac atgagctgtc 4980
ttcggtatcg tcgtatccca ctaccgagat atccgcacca acgcgcagcc cggactcggt 5040
aatggcgcgc attgcgccca gcgccatctg atcgttggca accagcatcg cagtgggaac 5100
gatgccctca ttcagcattt gcatggtttg ttgaaaaccg gacatggcac tccagtcgcc 5160
ttcccgttcc gctatcggct gaatttgatt gcgagtgaga tatttatgcc agccagccag 5220
acgcagacgc gccgagacag aacttaatgg gcccgctaac agcgcgattt gctggtgacc 5280
caatgcgacc agatgctcca cgcccagtcg cgtaccgtct tcatgggaga aaataatact 5340
gttgatgggt gtctggtcag agacatcaag aaataacgcc ggaacattag tgcaggcagc 5400
ttccacagca atggcatcct ggtcatccag cggatagtta atgatcagcc cactgacgcg 5460
ttgcgcgaga agattgtgca ccgccgcttt acaggcttcg acgccgcttc gttctaccat 5520
cgacaccacc acgctggcac ccagttgatc ggcgcgagat ttaatcgccg cgacaatttg 5580
cgacggcgcg tgcagggcca gactggaggt ggcaacgcca atcagcaacg actgtttgcc 5640
cgccagttgt tgtgccacgc ggttgggaat gtaattcagc tccgccatcg ccgcttccac 5700
tttttcccgc gttttcgcag aaacgtggct ggcctggttc accacgcggg aaacggtctg 5760
ataagagaca ccggcatact ctgcgacatc gtataacgtt actggtttca cattcaccac 5820
cctgaattga ctctcttccg ggcgctatca tgccataccg cgaaaggttt tgcgccattc 5880
gatggtgtcc gggatctcga cgctctccct tatgcgactc ctgcattagg aagcagccca 5940
gtagtaggtt gaggccgttg agcaccgccg ccgcaaggaa tggtgcatgc aaggagatgg 6000
cgcccaacag tcccccggcc acggggcctg ccaccatacc cacgccgaaa caagcgctca 6060
tgagcccgaa gtggcgagcc cgatcttccc catcggtgat gtcggcgata taggcgccag 6120
caaccgcacc tgtggcgccg gtgatgccgg ccacgatgcg tccggcgtag aggatcga 6178
<210> 103
<211> 6511
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 103
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat ggcagccaca 120
catgaacact ctgcccaatg gctgaacaac tacaaaaaag gctacggtta tggcccttac 180
cctctgggca ttaacggtgg catgcactac ggcgttgact tttttatgaa catcggcacc 240
cctgtgaaag ccattagctc aggcaaaatc gtggaagccg gttggtcaaa ctatggcggt 300
ggcaaccaga tcggtctgat cgagaacgat ggtgtgcacc gccaatggta catgcacctg 360
tccaaataca acgttaaagt tggtgactac gtgaaagcag gccagattat cggctggtca 420
ggttcaaccg gttattcaac agcccctcat ctgcacttcc aacgcatggt gaatagtttt 480
agtaattcta ccgctcaaga tccgatgcca ttcctgaaat ctgccggtta tggtggcaaa 540
ctggaagtta gcaaagcagc aaccattaaa cagtccgatg ttaaacaaga agtgaaaaaa 600
caagaggcca aacaaattgt gaaagcgacc gattggaaac agaacaaaga tggcatttgg 660
tataaagcag aacatgccag ctttaccgtg accgcaccgg aaggcattat tacccgttat 720
aaaggtccgt ggaccggtca tccgcaggca ggcgtgctgc agaaaggtca gaccatcaaa 780
tatgatgagg tgcagaaatt tgatggccat gtttgggtta gctgggaaac ctttgaaggt 840
gaaaccgttt atatgccggt tcgtacctgg gatgcaaaaa ccggtaaagt gggtaaactg 900
tggggtgaaa tcaaagagct ccgccagatc aaaatttggt ttcagaatcg tcgcatgaaa 960
tggaaaaaat aaggatccgg ctgctaacaa agcccgaaag gaagctgagt tggctgctgc 1020
caccgctgag caataactag cataacccct tggggcctct aaacgggtct tgaggggttt 1080
tttgctgaaa ggaggaacta tatccggata tcccgcaaga ggcccggcag taccggcata 1140
accaagccta tgcctacagc atccagggtg acggtgccga ggatgacgat gagcgcattg 1200
ttagatttca tacacggtgc ctgactgcgt tagcaattta actgtgataa actaccgcat 1260
taaagctagc ttatcgatga taagctgtca aacatgagaa ttaattcttg aagacgaaag 1320
ggcctcgtga tacgcctatt tttataggtt aatgtcatga taataatggt ttcttagacg 1380
tcaggtggca cttttcgggg aaatgtgcgc ggaaccccta tttgtttatt tttctaaata 1440
cattcaaata tgtatccgct catgagacaa taaccctgat aaatgcttca ataatattga 1500
aaaaggaaga gtatgagtat tcaacatttc cgtgtcgccc ttattccctt ttttgcggca 1560
ttttgccttc ctgtttttgc tcacccagaa acgctggtga aagtaaaaga tgctgaagat 1620
cagttgggtg cacgagtggg ttacatcgaa ctggatctca acagcggtaa gatccttgag 1680
agttttcgcc ccgaagaacg ttttccaatg atgagcactt ttaaagttct gctatgtggc 1740
gcggtattat cccgtgttga cgccgggcaa gagcaactcg gtcgccgcat acactattct 1800
cagaatgact tggttgagta ctcaccagtc acagaaaagc atcttacgga tggcatgaca 1860
gtaagagaat tatgcagtgc tgccataacc atgagtgata acactgcggc caacttactt 1920
ctgacaacga tcggaggacc gaaggagcta accgcttttt tgcacaacat gggggatcat 1980
gtaactcgcc ttgatcgttg ggaaccggag ctgaatgaag ccataccaaa cgacgagcgt 2040
gacaccacga tgcctgcagc aatggcaaca acgttgcgca aactattaac tggcgaacta 2100
cttactctag cttcccggca acaattaata gactggatgg aggcggataa agttgcagga 2160
ccacttctgc gctcggccct tccggctggc tggtttattg ctgataaatc tggagccggt 2220
gagcgtgggt ctcgcggtat cattgcagca ctggggccag atggtaagcc ctcccgtatc 2280
gtagttatct acacgacggg gagtcaggca actatggatg aacgaaatag acagatcgct 2340
gagataggtg cctcactgat taagcattgg taactgtcag accaagttta ctcatatata 2400
ctttagattg atttaaaact tcatttttaa tttaaaagga tctaggtgaa gatccttttt 2460
gataatctca tgaccaaaat cccttaacgt gagttttcgt tccactgagc gtcagacccc 2520
gtagaaaaga tcaaaggatc ttcttgagat cctttttttc tgcgcgtaat ctgctgcttg 2580
caaacaaaaa aaccaccgct accagcggtg gtttgtttgc cggatcaaga gctaccaact 2640
ctttttccga aggtaactgg cttcagcaga gcgcagatac caaatactgt ccttctagtg 2700
tagccgtagt taggccacca cttcaagaac tctgtagcac cgcctacata cctcgctctg 2760
ctaatcctgt taccagtggc tgctgccagt ggcgataagt cgtgtcttac cgggttggac 2820
tcaagacgat agttaccgga taaggcgcag cggtcgggct gaacgggggg ttcgtgcaca 2880
cagcccagct tggagcgaac gacctacacc gaactgagat acctacagcg tgagctatga 2940
gaaagcgcca cgcttcccga agggagaaag gcggacaggt atccggtaag cggcagggtc 3000
ggaacaggag agcgcacgag ggagcttcca gggggaaacg cctggtatct ttatagtcct 3060
gtcgggtttc gccacctctg acttgagcgt cgatttttgt gatgctcgtc aggggggcgg 3120
agcctatgga aaaacgccag caacgcggcc tttttacggt tcctggcctt ttgctggcct 3180
tttgctcaca tgttctttcc tgcgttatcc cctgattctg tggataaccg tattaccgcc 3240
tttgagtgag ctgataccgc tcgccgcagc cgaacgaccg agcgcagcga gtcagtgagc 3300
gaggaagcgg aagagcgcct gatgcggtat tttctcctta cgcatctgtg cggtatttca 3360
caccgcaatg gtgcactctc agtacaatct gctctgatgc cgcatagtta agccagtata 3420
cactccgcta tcgctacgtg actgggtcat ggctgcgccc cgacacccgc caacacccgc 3480
tgacgcgccc tgacgggctt gtctgctccc ggcatccgct tacagacaag ctgtgaccgt 3540
ctccgggagc tgcatgtgtc agaggttttc accgtcatca ccgaaacgcg cgaggcagct 3600
gcggtaaagc tcatcagcgt ggtcgtgaag cgattcacag atgtctgcct gttcatccgc 3660
gtccagctcg ttgagtttct ccagaagcgt taatgtctgg cttctgataa agcgggccat 3720
gttaagggcg gttttttcct gtttggtcac tgatgcctcc gtgtaagggg gatttctgtt 3780
catgggggta atgataccga tgaaacgaga gaggatgctc acgatacggg ttactgatga 3840
tgaacatgcc cggttactgg aacgttgtga gggtaaacaa ctggcggtat ggatgcggcg 3900
ggaccagaga aaaatcactc agggtcaatg ccagcgcttc gttaatacag atgtaggtgt 3960
tccacagggt agccagcagc atcctgcgat gcagatccgg aacataatgg tgcagggcgc 4020
tgacttccgc gtttccagac tttacgaaac acggaaaccg aagaccattc atgttgttgc 4080
tcaggtcgca gacgttttgc agcagcagtc gcttcacgtt cgctcgcgta tcggtgattc 4140
attctgctaa ccagtaaggc aaccccgcca gcctagccgg gtcctcaacg acaggagcac 4200
gatcatgcgc acccgtggcc aggacccaac gctgcccgag atgcgccgcg tgcggctgct 4260
ggagatggcg gacgcgatgg atatgttctg ccaagggttg gtttgcgcat tcacagttct 4320
ccgcaagaat tgattggctc caattcttgg agtggtgaat ccgttagcga ggtgccgccg 4380
gcttccattc aggtcgaggt ggcccggctc catgcaccgc gacgcaacgc ggggaggcag 4440
acaaggtata gggcggcgcc tacaatccat gccaacccgt tccatgtgct cgccgaggcg 4500
gcataaatcg ccgtgacgat cagcggtcca atgatcgaag ttaggctggt aagagccgcg 4560
agcgatcctt gaagctgtcc ctgatggtcg tcatctacct gcctggacag catggcctgc 4620
aacgcgggca tcccgatgcc gccggaagcg agaagaatca taatggggaa ggccatccag 4680
cctcgcgtcg cgaacgccag caagacgtag cccagcgcgt cggccgccat gccggcgata 4740
atggcctgct tctcgccgaa acgtttggtg gcgggaccag tgacgaaggc ttgagcgagg 4800
gcgtgcaaga ttccgaatac cgcaagcgac aggccgatca tcgtcgcgct ccagcgaaag 4860
cggtcctcgc cgaaaatgac ccagagcgct gccggcacct gtcctacgag ttgcatgata 4920
aagaagacag tcataagtgc ggcgacgata gtcatgcccc gcgcccaccg gaaggagctg 4980
actgggttga aggctctcaa gggcatcggt cgagatcccg gtgcctaatg agtgagctaa 5040
cttacattaa ttgcgttgcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag 5100
ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgccagggt 5160
ggtttttctt ttcaccagtg agacgggcaa cagctgattg cccttcaccg cctggccctg 5220
agagagttgc agcaagcggt ccacgctggt ttgccccagc aggcgaaaat cctgtttgat 5280
ggtggttaac ggcgggatat aacatgagct gtcttcggta tcgtcgtatc ccactaccga 5340
gatatccgca ccaacgcgca gcccggactc ggtaatggcg cgcattgcgc ccagcgccat 5400
ctgatcgttg gcaaccagca tcgcagtggg aacgatgccc tcattcagca tttgcatggt 5460
ttgttgaaaa ccggacatgg cactccagtc gccttcccgt tccgctatcg gctgaatttg 5520
attgcgagtg agatatttat gccagccagc cagacgcaga cgcgccgaga cagaacttaa 5580
tgggcccgct aacagcgcga tttgctggtg acccaatgcg accagatgct ccacgcccag 5640
tcgcgtaccg tcttcatggg agaaaataat actgttgatg ggtgtctggt cagagacatc 5700
aagaaataac gccggaacat tagtgcaggc agcttccaca gcaatggcat cctggtcatc 5760
cagcggatag ttaatgatca gcccactgac gcgttgcgcg agaagattgt gcaccgccgc 5820
tttacaggct tcgacgccgc ttcgttctac catcgacacc accacgctgg cacccagttg 5880
atcggcgcga gatttaatcg ccgcgacaat ttgcgacggc gcgtgcaggg ccagactgga 5940
ggtggcaacg ccaatcagca acgactgttt gcccgccagt tgttgtgcca cgcggttggg 6000
aatgtaattc agctccgcca tcgccgcttc cactttttcc cgcgttttcg cagaaacgtg 6060
gctggcctgg ttcaccacgc gggaaacggt ctgataagag acaccggcat actctgcgac 6120
atcgtataac gttactggtt tcacattcac caccctgaat tgactctctt ccgggcgcta 6180
tcatgccata ccgcgaaagg ttttgcgcca ttcgatggtg tccgggatct cgacgctctc 6240
ccttatgcga ctcctgcatt aggaagcagc ccagtagtag gttgaggccg ttgagcaccg 6300
ccgccgcaag gaatggtgca tgcaaggaga tggcgcccaa cagtcccccg gccacggggc 6360
ctgccaccat acccacgccg aaacaagcgc tcatgagccc gaagtggcga gcccgatctt 6420
ccccatcggt gatgtcggcg atataggcgc cagcaaccgc acctgtggcg ccggtgatgc 6480
cggccacgat gcgtccggcg tagaggatcg a 6511
<210> 104
<211> 6490
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 104
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat ggcagccaca 120
catgaacact ctgcccaatg gctgaacaac tacaaaaaag gctacggtta tggcccttac 180
cctctgggca ttaacggtgg catgcactac ggcgttgact tttttatgaa catcggcacc 240
cctgtgaaag ccattagctc aggcaaaatc gtggaagccg gttggtcaaa ctatggcggt 300
ggcaaccaga tcggtctgat cgagaacgat ggtgtgcacc gccaatggta catgcacctg 360
tccaaataca acgttaaagt tggtgactac gtgaaagcag gccagattat cggctggtca 420
ggttcaaccg gttattcaac agcccctcat ctgcacttcc aacgcatggt gaatagtttt 480
agtaattcta ccgctcaaga tccgatgcca ttcctgaaat ctgccggtta tggtggcaaa 540
ctggaagtta gcaaagcagc aaccattaaa cagtccgatg ttaaacaaga agtgaaaaaa 600
caagaggcca aacaaattgt gaaagcgacc gattggaaac agaacaaaga tggcatttgg 660
tataaagcag aacatgccag ctttaccgtg accgcaccgg aaggcattat tacccgttat 720
aaaggtccgt ggaccggtca tccgcaggca ggcgtgctgc agaaaggtca gaccatcaaa 780
tatgatgagg tgcagaaatt tgatggccat gtttgggtta gctgggaaac ctttgaaggt 840
gaaaccgttt atatgccggt tcgtacctgg gatgcaaaaa ccggtaaagt gggtaaactg 900
tggggtgaaa tcaaagagct ccgtcgtcgt cgccgtcggc gtcgtcgtta aggatccggc 960
tgctaacaaa gcccgaaagg aagctgagtt ggctgctgcc accgctgagc aataactagc 1020
ataacccctt ggggcctcta aacgggtctt gaggggtttt ttgctgaaag gaggaactat 1080
atccggatat cccgcaagag gcccggcagt accggcataa ccaagcctat gcctacagca 1140
tccagggtga cggtgccgag gatgacgatg agcgcattgt tagatttcat acacggtgcc 1200
tgactgcgtt agcaatttaa ctgtgataaa ctaccgcatt aaagctagct tatcgatgat 1260
aagctgtcaa acatgagaat taattcttga agacgaaagg gcctcgtgat acgcctattt 1320
ttataggtta atgtcatgat aataatggtt tcttagacgt caggtggcac ttttcgggga 1380
aatgtgcgcg gaacccctat ttgtttattt ttctaaatac attcaaatat gtatccgctc 1440
atgagacaat aaccctgata aatgcttcaa taatattgaa aaaggaagag tatgagtatt 1500
caacatttcc gtgtcgccct tattcccttt tttgcggcat tttgccttcc tgtttttgct 1560
cacccagaaa cgctggtgaa agtaaaagat gctgaagatc agttgggtgc acgagtgggt 1620
tacatcgaac tggatctcaa cagcggtaag atccttgaga gttttcgccc cgaagaacgt 1680
tttccaatga tgagcacttt taaagttctg ctatgtggcg cggtattatc ccgtgttgac 1740
gccgggcaag agcaactcgg tcgccgcata cactattctc agaatgactt ggttgagtac 1800
tcaccagtca cagaaaagca tcttacggat ggcatgacag taagagaatt atgcagtgct 1860
gccataacca tgagtgataa cactgcggcc aacttacttc tgacaacgat cggaggaccg 1920
aaggagctaa ccgctttttt gcacaacatg ggggatcatg taactcgcct tgatcgttgg 1980
gaaccggagc tgaatgaagc cataccaaac gacgagcgtg acaccacgat gcctgcagca 2040
atggcaacaa cgttgcgcaa actattaact ggcgaactac ttactctagc ttcccggcaa 2100
caattaatag actggatgga ggcggataaa gttgcaggac cacttctgcg ctcggccctt 2160
ccggctggct ggtttattgc tgataaatct ggagccggtg agcgtgggtc tcgcggtatc 2220
attgcagcac tggggccaga tggtaagccc tcccgtatcg tagttatcta cacgacgggg 2280
agtcaggcaa ctatggatga acgaaataga cagatcgctg agataggtgc ctcactgatt 2340
aagcattggt aactgtcaga ccaagtttac tcatatatac tttagattga tttaaaactt 2400
catttttaat ttaaaaggat ctaggtgaag atcctttttg ataatctcat gaccaaaatc 2460
ccttaacgtg agttttcgtt ccactgagcg tcagaccccg tagaaaagat caaaggatct 2520
tcttgagatc ctttttttct gcgcgtaatc tgctgcttgc aaacaaaaaa accaccgcta 2580
ccagcggtgg tttgtttgcc ggatcaagag ctaccaactc tttttccgaa ggtaactggc 2640
ttcagcagag cgcagatacc aaatactgtc cttctagtgt agccgtagtt aggccaccac 2700
ttcaagaact ctgtagcacc gcctacatac ctcgctctgc taatcctgtt accagtggct 2760
gctgccagtg gcgataagtc gtgtcttacc gggttggact caagacgata gttaccggat 2820
aaggcgcagc ggtcgggctg aacggggggt tcgtgcacac agcccagctt ggagcgaacg 2880
acctacaccg aactgagata cctacagcgt gagctatgag aaagcgccac gcttcccgaa 2940
gggagaaagg cggacaggta tccggtaagc ggcagggtcg gaacaggaga gcgcacgagg 3000
gagcttccag ggggaaacgc ctggtatctt tatagtcctg tcgggtttcg ccacctctga 3060
cttgagcgtc gatttttgtg atgctcgtca ggggggcgga gcctatggaa aaacgccagc 3120
aacgcggcct ttttacggtt cctggccttt tgctggcctt ttgctcacat gttctttcct 3180
gcgttatccc ctgattctgt ggataaccgt attaccgcct ttgagtgagc tgataccgct 3240
cgccgcagcc gaacgaccga gcgcagcgag tcagtgagcg aggaagcgga agagcgcctg 3300
atgcggtatt ttctccttac gcatctgtgc ggtatttcac accgcaatgg tgcactctca 3360
gtacaatctg ctctgatgcc gcatagttaa gccagtatac actccgctat cgctacgtga 3420
ctgggtcatg gctgcgcccc gacacccgcc aacacccgct gacgcgccct gacgggcttg 3480
tctgctcccg gcatccgctt acagacaagc tgtgaccgtc tccgggagct gcatgtgtca 3540
gaggttttca ccgtcatcac cgaaacgcgc gaggcagctg cggtaaagct catcagcgtg 3600
gtcgtgaagc gattcacaga tgtctgcctg ttcatccgcg tccagctcgt tgagtttctc 3660
cagaagcgtt aatgtctggc ttctgataaa gcgggccatg ttaagggcgg ttttttcctg 3720
tttggtcact gatgcctccg tgtaaggggg atttctgttc atgggggtaa tgataccgat 3780
gaaacgagag aggatgctca cgatacgggt tactgatgat gaacatgccc ggttactgga 3840
acgttgtgag ggtaaacaac tggcggtatg gatgcggcgg gaccagagaa aaatcactca 3900
gggtcaatgc cagcgcttcg ttaatacaga tgtaggtgtt ccacagggta gccagcagca 3960
tcctgcgatg cagatccgga acataatggt gcagggcgct gacttccgcg tttccagact 4020
ttacgaaaca cggaaaccga agaccattca tgttgttgct caggtcgcag acgttttgca 4080
gcagcagtcg cttcacgttc gctcgcgtat cggtgattca ttctgctaac cagtaaggca 4140
accccgccag cctagccggg tcctcaacga caggagcacg atcatgcgca cccgtggcca 4200
ggacccaacg ctgcccgaga tgcgccgcgt gcggctgctg gagatggcgg acgcgatgga 4260
tatgttctgc caagggttgg tttgcgcatt cacagttctc cgcaagaatt gattggctcc 4320
aattcttgga gtggtgaatc cgttagcgag gtgccgccgg cttccattca ggtcgaggtg 4380
gcccggctcc atgcaccgcg acgcaacgcg gggaggcaga caaggtatag ggcggcgcct 4440
acaatccatg ccaacccgtt ccatgtgctc gccgaggcgg cataaatcgc cgtgacgatc 4500
agcggtccaa tgatcgaagt taggctggta agagccgcga gcgatccttg aagctgtccc 4560
tgatggtcgt catctacctg cctggacagc atggcctgca acgcgggcat cccgatgccg 4620
ccggaagcga gaagaatcat aatggggaag gccatccagc ctcgcgtcgc gaacgccagc 4680
aagacgtagc ccagcgcgtc ggccgccatg ccggcgataa tggcctgctt ctcgccgaaa 4740
cgtttggtgg cgggaccagt gacgaaggct tgagcgaggg cgtgcaagat tccgaatacc 4800
gcaagcgaca ggccgatcat cgtcgcgctc cagcgaaagc ggtcctcgcc gaaaatgacc 4860
cagagcgctg ccggcacctg tcctacgagt tgcatgataa agaagacagt cataagtgcg 4920
gcgacgatag tcatgccccg cgcccaccgg aaggagctga ctgggttgaa ggctctcaag 4980
ggcatcggtc gagatcccgg tgcctaatga gtgagctaac ttacattaat tgcgttgcgc 5040
tcactgcccg ctttccagtc gggaaacctg tcgtgccagc tgcattaatg aatcggccaa 5100
cgcgcgggga gaggcggttt gcgtattggg cgccagggtg gtttttcttt tcaccagtga 5160
gacgggcaac agctgattgc ccttcaccgc ctggccctga gagagttgca gcaagcggtc 5220
cacgctggtt tgccccagca ggcgaaaatc ctgtttgatg gtggttaacg gcgggatata 5280
acatgagctg tcttcggtat cgtcgtatcc cactaccgag atatccgcac caacgcgcag 5340
cccggactcg gtaatggcgc gcattgcgcc cagcgccatc tgatcgttgg caaccagcat 5400
cgcagtggga acgatgccct cattcagcat ttgcatggtt tgttgaaaac cggacatggc 5460
actccagtcg ccttcccgtt ccgctatcgg ctgaatttga ttgcgagtga gatatttatg 5520
ccagccagcc agacgcagac gcgccgagac agaacttaat gggcccgcta acagcgcgat 5580
ttgctggtga cccaatgcga ccagatgctc cacgcccagt cgcgtaccgt cttcatggga 5640
gaaaataata ctgttgatgg gtgtctggtc agagacatca agaaataacg ccggaacatt 5700
agtgcaggca gcttccacag caatggcatc ctggtcatcc agcggatagt taatgatcag 5760
cccactgacg cgttgcgcga gaagattgtg caccgccgct ttacaggctt cgacgccgct 5820
tcgttctacc atcgacacca ccacgctggc acccagttga tcggcgcgag atttaatcgc 5880
cgcgacaatt tgcgacggcg cgtgcagggc cagactggag gtggcaacgc caatcagcaa 5940
cgactgtttg cccgccagtt gttgtgccac gcggttggga atgtaattca gctccgccat 6000
cgccgcttcc actttttccc gcgttttcgc agaaacgtgg ctggcctggt tcaccacgcg 6060
ggaaacggtc tgataagaga caccggcata ctctgcgaca tcgtataacg ttactggttt 6120
cacattcacc accctgaatt gactctcttc cgggcgctat catgccatac cgcgaaaggt 6180
tttgcgccat tcgatggtgt ccgggatctc gacgctctcc cttatgcgac tcctgcatta 6240
ggaagcagcc cagtagtagg ttgaggccgt tgagcaccgc cgccgcaagg aatggtgcat 6300
gcaaggagat ggcgcccaac agtcccccgg ccacggggcc tgccaccata cccacgccga 6360
aacaagcgct catgagcccg aagtggcgag cccgatcttc cccatcggtg atgtcggcga 6420
tataggcgcc agcaaccgca cctgtggcgc cggtgatgcc ggccacgatg cgtccggcgt 6480
agaggatcga 6490
<210> 105
<211> 6502
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 105
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat ggcagccaca 120
catgaacact ctgcccaatg gctgaacaac tacaaaaaag gctacggtta tggcccttac 180
cctctgggca ttaacggtgg catgcactac ggcgttgact tttttatgaa catcggcacc 240
cctgtgaaag ccattagctc aggcaaaatc gtggaagccg gttggtcaaa ctatggcggt 300
ggcaaccaga tcggtctgat cgagaacgat ggtgtgcacc gccaatggta catgcacctg 360
tccaaataca acgttaaagt tggtgactac gtgaaagcag gccagattat cggctggtca 420
ggttcaaccg gttattcaac agcccctcat ctgcacttcc aacgcatggt gaatagtttt 480
agtaattcta ccgctcaaga tccgatgcca ttcctgaaat ctgccggtta tggtggcaaa 540
ctggaagtta gcaaagcagc aaccattaaa cagtccgatg ttaaacaaga agtgaaaaaa 600
caagaggcca aacaaattgt gaaagcgacc gattggaaac agaacaaaga tggcatttgg 660
tataaagcag aacatgccag ctttaccgtg accgcaccgg aaggcattat tacccgttat 720
aaaggtccgt ggaccggtca tccgcaggca ggcgtgctgc agaaaggtca gaccatcaaa 780
tatgatgagg tgcagaaatt tgatggccat gtttgggtta gctgggaaac ctttgaaggt 840
gaaaccgttt atatgccggt tcgtacctgg gatgcaaaaa ccggtaaagt gggtaaactg 900
tggggtgaaa tcaaagagct cggtcgtaaa aaacgtcgtc agcgtcgtcg tccgcctcag 960
taaggatccg gctgctaaca aagcccgaaa ggaagctgag ttggctgctg ccaccgctga 1020
gcaataacta gcataacccc ttggggcctc taaacgggtc ttgaggggtt ttttgctgaa 1080
aggaggaact atatccggat atcccgcaag aggcccggca gtaccggcat aaccaagcct 1140
atgcctacag catccagggt gacggtgccg aggatgacga tgagcgcatt gttagatttc 1200
atacacggtg cctgactgcg ttagcaattt aactgtgata aactaccgca ttaaagctag 1260
cttatcgatg ataagctgtc aaacatgaga attaattctt gaagacgaaa gggcctcgtg 1320
atacgcctat ttttataggt taatgtcatg ataataatgg tttcttagac gtcaggtggc 1380
acttttcggg gaaatgtgcg cggaacccct atttgtttat ttttctaaat acattcaaat 1440
atgtatccgc tcatgagaca ataaccctga taaatgcttc aataatattg aaaaaggaag 1500
agtatgagta ttcaacattt ccgtgtcgcc cttattccct tttttgcggc attttgcctt 1560
cctgtttttg ctcacccaga aacgctggtg aaagtaaaag atgctgaaga tcagttgggt 1620
gcacgagtgg gttacatcga actggatctc aacagcggta agatccttga gagttttcgc 1680
cccgaagaac gttttccaat gatgagcact tttaaagttc tgctatgtgg cgcggtatta 1740
tcccgtgttg acgccgggca agagcaactc ggtcgccgca tacactattc tcagaatgac 1800
ttggttgagt actcaccagt cacagaaaag catcttacgg atggcatgac agtaagagaa 1860
ttatgcagtg ctgccataac catgagtgat aacactgcgg ccaacttact tctgacaacg 1920
atcggaggac cgaaggagct aaccgctttt ttgcacaaca tgggggatca tgtaactcgc 1980
cttgatcgtt gggaaccgga gctgaatgaa gccataccaa acgacgagcg tgacaccacg 2040
atgcctgcag caatggcaac aacgttgcgc aaactattaa ctggcgaact acttactcta 2100
gcttcccggc aacaattaat agactggatg gaggcggata aagttgcagg accacttctg 2160
cgctcggccc ttccggctgg ctggtttatt gctgataaat ctggagccgg tgagcgtggg 2220
tctcgcggta tcattgcagc actggggcca gatggtaagc cctcccgtat cgtagttatc 2280
tacacgacgg ggagtcaggc aactatggat gaacgaaata gacagatcgc tgagataggt 2340
gcctcactga ttaagcattg gtaactgtca gaccaagttt actcatatat actttagatt 2400
gatttaaaac ttcattttta atttaaaagg atctaggtga agatcctttt tgataatctc 2460
atgaccaaaa tcccttaacg tgagttttcg ttccactgag cgtcagaccc cgtagaaaag 2520
atcaaaggat cttcttgaga tccttttttt ctgcgcgtaa tctgctgctt gcaaacaaaa 2580
aaaccaccgc taccagcggt ggtttgtttg ccggatcaag agctaccaac tctttttccg 2640
aaggtaactg gcttcagcag agcgcagata ccaaatactg tccttctagt gtagccgtag 2700
ttaggccacc acttcaagaa ctctgtagca ccgcctacat acctcgctct gctaatcctg 2760
ttaccagtgg ctgctgccag tggcgataag tcgtgtctta ccgggttgga ctcaagacga 2820
tagttaccgg ataaggcgca gcggtcgggc tgaacggggg gttcgtgcac acagcccagc 2880
ttggagcgaa cgacctacac cgaactgaga tacctacagc gtgagctatg agaaagcgcc 2940
acgcttcccg aagggagaaa ggcggacagg tatccggtaa gcggcagggt cggaacagga 3000
gagcgcacga gggagcttcc agggggaaac gcctggtatc tttatagtcc tgtcgggttt 3060
cgccacctct gacttgagcg tcgatttttg tgatgctcgt caggggggcg gagcctatgg 3120
aaaaacgcca gcaacgcggc ctttttacgg ttcctggcct tttgctggcc ttttgctcac 3180
atgttctttc ctgcgttatc ccctgattct gtggataacc gtattaccgc ctttgagtga 3240
gctgataccg ctcgccgcag ccgaacgacc gagcgcagcg agtcagtgag cgaggaagcg 3300
gaagagcgcc tgatgcggta ttttctcctt acgcatctgt gcggtatttc acaccgcaat 3360
ggtgcactct cagtacaatc tgctctgatg ccgcatagtt aagccagtat acactccgct 3420
atcgctacgt gactgggtca tggctgcgcc ccgacacccg ccaacacccg ctgacgcgcc 3480
ctgacgggct tgtctgctcc cggcatccgc ttacagacaa gctgtgaccg tctccgggag 3540
ctgcatgtgt cagaggtttt caccgtcatc accgaaacgc gcgaggcagc tgcggtaaag 3600
ctcatcagcg tggtcgtgaa gcgattcaca gatgtctgcc tgttcatccg cgtccagctc 3660
gttgagtttc tccagaagcg ttaatgtctg gcttctgata aagcgggcca tgttaagggc 3720
ggttttttcc tgtttggtca ctgatgcctc cgtgtaaggg ggatttctgt tcatgggggt 3780
aatgataccg atgaaacgag agaggatgct cacgatacgg gttactgatg atgaacatgc 3840
ccggttactg gaacgttgtg agggtaaaca actggcggta tggatgcggc gggaccagag 3900
aaaaatcact cagggtcaat gccagcgctt cgttaataca gatgtaggtg ttccacaggg 3960
tagccagcag catcctgcga tgcagatccg gaacataatg gtgcagggcg ctgacttccg 4020
cgtttccaga ctttacgaaa cacggaaacc gaagaccatt catgttgttg ctcaggtcgc 4080
agacgttttg cagcagcagt cgcttcacgt tcgctcgcgt atcggtgatt cattctgcta 4140
accagtaagg caaccccgcc agcctagccg ggtcctcaac gacaggagca cgatcatgcg 4200
cacccgtggc caggacccaa cgctgcccga gatgcgccgc gtgcggctgc tggagatggc 4260
ggacgcgatg gatatgttct gccaagggtt ggtttgcgca ttcacagttc tccgcaagaa 4320
ttgattggct ccaattcttg gagtggtgaa tccgttagcg aggtgccgcc ggcttccatt 4380
caggtcgagg tggcccggct ccatgcaccg cgacgcaacg cggggaggca gacaaggtat 4440
agggcggcgc ctacaatcca tgccaacccg ttccatgtgc tcgccgaggc ggcataaatc 4500
gccgtgacga tcagcggtcc aatgatcgaa gttaggctgg taagagccgc gagcgatcct 4560
tgaagctgtc cctgatggtc gtcatctacc tgcctggaca gcatggcctg caacgcgggc 4620
atcccgatgc cgccggaagc gagaagaatc ataatgggga aggccatcca gcctcgcgtc 4680
gcgaacgcca gcaagacgta gcccagcgcg tcggccgcca tgccggcgat aatggcctgc 4740
ttctcgccga aacgtttggt ggcgggacca gtgacgaagg cttgagcgag ggcgtgcaag 4800
attccgaata ccgcaagcga caggccgatc atcgtcgcgc tccagcgaaa gcggtcctcg 4860
ccgaaaatga cccagagcgc tgccggcacc tgtcctacga gttgcatgat aaagaagaca 4920
gtcataagtg cggcgacgat agtcatgccc cgcgcccacc ggaaggagct gactgggttg 4980
aaggctctca agggcatcgg tcgagatccc ggtgcctaat gagtgagcta acttacatta 5040
attgcgttgc gctcactgcc cgctttccag tcgggaaacc tgtcgtgcca gctgcattaa 5100
tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg ggcgccaggg tggtttttct 5160
tttcaccagt gagacgggca acagctgatt gcccttcacc gcctggccct gagagagttg 5220
cagcaagcgg tccacgctgg tttgccccag caggcgaaaa tcctgtttga tggtggttaa 5280
cggcgggata taacatgagc tgtcttcggt atcgtcgtat cccactaccg agatatccgc 5340
accaacgcgc agcccggact cggtaatggc gcgcattgcg cccagcgcca tctgatcgtt 5400
ggcaaccagc atcgcagtgg gaacgatgcc ctcattcagc atttgcatgg tttgttgaaa 5460
accggacatg gcactccagt cgccttcccg ttccgctatc ggctgaattt gattgcgagt 5520
gagatattta tgccagccag ccagacgcag acgcgccgag acagaactta atgggcccgc 5580
taacagcgcg atttgctggt gacccaatgc gaccagatgc tccacgccca gtcgcgtacc 5640
gtcttcatgg gagaaaataa tactgttgat gggtgtctgg tcagagacat caagaaataa 5700
cgccggaaca ttagtgcagg cagcttccac agcaatggca tcctggtcat ccagcggata 5760
gttaatgatc agcccactga cgcgttgcgc gagaagattg tgcaccgccg ctttacaggc 5820
ttcgacgccg cttcgttcta ccatcgacac caccacgctg gcacccagtt gatcggcgcg 5880
agatttaatc gccgcgacaa tttgcgacgg cgcgtgcagg gccagactgg aggtggcaac 5940
gccaatcagc aacgactgtt tgcccgccag ttgttgtgcc acgcggttgg gaatgtaatt 6000
cagctccgcc atcgccgctt ccactttttc ccgcgttttc gcagaaacgt ggctggcctg 6060
gttcaccacg cgggaaacgg tctgataaga gacaccggca tactctgcga catcgtataa 6120
cgttactggt ttcacattca ccaccctgaa ttgactctct tccgggcgct atcatgccat 6180
accgcgaaag gttttgcgcc attcgatggt gtccgggatc tcgacgctct cccttatgcg 6240
actcctgcat taggaagcag cccagtagta ggttgaggcc gttgagcacc gccgccgcaa 6300
ggaatggtgc atgcaaggag atggcgccca acagtccccc ggccacgggg cctgccacca 6360
tacccacgcc gaaacaagcg ctcatgagcc cgaagtggcg agcccgatct tccccatcgg 6420
tgatgtcggc gatataggcg ccagcaaccg cacctgtggc gccggtgatg ccggccacga 6480
tgcgtccggc gtagaggatc ga 6502
<210> 106
<211> 6130
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 106
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat ggcagccaca 120
catgaacact ctgcccaatg gctgaacaac tacaaaaaag gctacggtta tggcccttac 180
cctctgggca ttaacggtgg catgcactac ggcgttgact tttttatgaa catcggcacc 240
cctgtgaaag ccattagctc aggcaaaatc gtggaagccg gttggtcaaa ctatggcggt 300
ggcaaccaga tcggtctgat cgagaacgat ggtgtgcacc gccaatggta catgcacctg 360
tccaaataca acgttaaagt tggtgactac gtgaaagcag gccagattat cggctggtca 420
ggttcaaccg gttattcaac agcccctcat ctgcacttcc aacgcatggt gaatagtttt 480
agtaattcta ccgctcaaga tccgatgcca ttcctgaaat ctgccggtta tggtgagctc 540
cgccagatca aaatttggtt tcagaatcgt cgcatgaaat ggaaaaaata aggatccggc 600
tgctaacaaa gcccgaaagg aagctgagtt ggctgctgcc accgctgagc aataactagc 660
ataacccctt ggggcctcta aacgggtctt gaggggtttt ttgctgaaag gaggaactat 720
atccggatat cccgcaagag gcccggcagt accggcataa ccaagcctat gcctacagca 780
tccagggtga cggtgccgag gatgacgatg agcgcattgt tagatttcat acacggtgcc 840
tgactgcgtt agcaatttaa ctgtgataaa ctaccgcatt aaagctagct tatcgatgat 900
aagctgtcaa acatgagaat taattcttga agacgaaagg gcctcgtgat acgcctattt 960
ttataggtta atgtcatgat aataatggtt tcttagacgt caggtggcac ttttcgggga 1020
aatgtgcgcg gaacccctat ttgtttattt ttctaaatac attcaaatat gtatccgctc 1080
atgagacaat aaccctgata aatgcttcaa taatattgaa aaaggaagag tatgagtatt 1140
caacatttcc gtgtcgccct tattcccttt tttgcggcat tttgccttcc tgtttttgct 1200
cacccagaaa cgctggtgaa agtaaaagat gctgaagatc agttgggtgc acgagtgggt 1260
tacatcgaac tggatctcaa cagcggtaag atccttgaga gttttcgccc cgaagaacgt 1320
tttccaatga tgagcacttt taaagttctg ctatgtggcg cggtattatc ccgtgttgac 1380
gccgggcaag agcaactcgg tcgccgcata cactattctc agaatgactt ggttgagtac 1440
tcaccagtca cagaaaagca tcttacggat ggcatgacag taagagaatt atgcagtgct 1500
gccataacca tgagtgataa cactgcggcc aacttacttc tgacaacgat cggaggaccg 1560
aaggagctaa ccgctttttt gcacaacatg ggggatcatg taactcgcct tgatcgttgg 1620
gaaccggagc tgaatgaagc cataccaaac gacgagcgtg acaccacgat gcctgcagca 1680
atggcaacaa cgttgcgcaa actattaact ggcgaactac ttactctagc ttcccggcaa 1740
caattaatag actggatgga ggcggataaa gttgcaggac cacttctgcg ctcggccctt 1800
ccggctggct ggtttattgc tgataaatct ggagccggtg agcgtgggtc tcgcggtatc 1860
attgcagcac tggggccaga tggtaagccc tcccgtatcg tagttatcta cacgacgggg 1920
agtcaggcaa ctatggatga acgaaataga cagatcgctg agataggtgc ctcactgatt 1980
aagcattggt aactgtcaga ccaagtttac tcatatatac tttagattga tttaaaactt 2040
catttttaat ttaaaaggat ctaggtgaag atcctttttg ataatctcat gaccaaaatc 2100
ccttaacgtg agttttcgtt ccactgagcg tcagaccccg tagaaaagat caaaggatct 2160
tcttgagatc ctttttttct gcgcgtaatc tgctgcttgc aaacaaaaaa accaccgcta 2220
ccagcggtgg tttgtttgcc ggatcaagag ctaccaactc tttttccgaa ggtaactggc 2280
ttcagcagag cgcagatacc aaatactgtc cttctagtgt agccgtagtt aggccaccac 2340
ttcaagaact ctgtagcacc gcctacatac ctcgctctgc taatcctgtt accagtggct 2400
gctgccagtg gcgataagtc gtgtcttacc gggttggact caagacgata gttaccggat 2460
aaggcgcagc ggtcgggctg aacggggggt tcgtgcacac agcccagctt ggagcgaacg 2520
acctacaccg aactgagata cctacagcgt gagctatgag aaagcgccac gcttcccgaa 2580
gggagaaagg cggacaggta tccggtaagc ggcagggtcg gaacaggaga gcgcacgagg 2640
gagcttccag ggggaaacgc ctggtatctt tatagtcctg tcgggtttcg ccacctctga 2700
cttgagcgtc gatttttgtg atgctcgtca ggggggcgga gcctatggaa aaacgccagc 2760
aacgcggcct ttttacggtt cctggccttt tgctggcctt ttgctcacat gttctttcct 2820
gcgttatccc ctgattctgt ggataaccgt attaccgcct ttgagtgagc tgataccgct 2880
cgccgcagcc gaacgaccga gcgcagcgag tcagtgagcg aggaagcgga agagcgcctg 2940
atgcggtatt ttctccttac gcatctgtgc ggtatttcac accgcaatgg tgcactctca 3000
gtacaatctg ctctgatgcc gcatagttaa gccagtatac actccgctat cgctacgtga 3060
ctgggtcatg gctgcgcccc gacacccgcc aacacccgct gacgcgccct gacgggcttg 3120
tctgctcccg gcatccgctt acagacaagc tgtgaccgtc tccgggagct gcatgtgtca 3180
gaggttttca ccgtcatcac cgaaacgcgc gaggcagctg cggtaaagct catcagcgtg 3240
gtcgtgaagc gattcacaga tgtctgcctg ttcatccgcg tccagctcgt tgagtttctc 3300
cagaagcgtt aatgtctggc ttctgataaa gcgggccatg ttaagggcgg ttttttcctg 3360
tttggtcact gatgcctccg tgtaaggggg atttctgttc atgggggtaa tgataccgat 3420
gaaacgagag aggatgctca cgatacgggt tactgatgat gaacatgccc ggttactgga 3480
acgttgtgag ggtaaacaac tggcggtatg gatgcggcgg gaccagagaa aaatcactca 3540
gggtcaatgc cagcgcttcg ttaatacaga tgtaggtgtt ccacagggta gccagcagca 3600
tcctgcgatg cagatccgga acataatggt gcagggcgct gacttccgcg tttccagact 3660
ttacgaaaca cggaaaccga agaccattca tgttgttgct caggtcgcag acgttttgca 3720
gcagcagtcg cttcacgttc gctcgcgtat cggtgattca ttctgctaac cagtaaggca 3780
accccgccag cctagccggg tcctcaacga caggagcacg atcatgcgca cccgtggcca 3840
ggacccaacg ctgcccgaga tgcgccgcgt gcggctgctg gagatggcgg acgcgatgga 3900
tatgttctgc caagggttgg tttgcgcatt cacagttctc cgcaagaatt gattggctcc 3960
aattcttgga gtggtgaatc cgttagcgag gtgccgccgg cttccattca ggtcgaggtg 4020
gcccggctcc atgcaccgcg acgcaacgcg gggaggcaga caaggtatag ggcggcgcct 4080
acaatccatg ccaacccgtt ccatgtgctc gccgaggcgg cataaatcgc cgtgacgatc 4140
agcggtccaa tgatcgaagt taggctggta agagccgcga gcgatccttg aagctgtccc 4200
tgatggtcgt catctacctg cctggacagc atggcctgca acgcgggcat cccgatgccg 4260
ccggaagcga gaagaatcat aatggggaag gccatccagc ctcgcgtcgc gaacgccagc 4320
aagacgtagc ccagcgcgtc ggccgccatg ccggcgataa tggcctgctt ctcgccgaaa 4380
cgtttggtgg cgggaccagt gacgaaggct tgagcgaggg cgtgcaagat tccgaatacc 4440
gcaagcgaca ggccgatcat cgtcgcgctc cagcgaaagc ggtcctcgcc gaaaatgacc 4500
cagagcgctg ccggcacctg tcctacgagt tgcatgataa agaagacagt cataagtgcg 4560
gcgacgatag tcatgccccg cgcccaccgg aaggagctga ctgggttgaa ggctctcaag 4620
ggcatcggtc gagatcccgg tgcctaatga gtgagctaac ttacattaat tgcgttgcgc 4680
tcactgcccg ctttccagtc gggaaacctg tcgtgccagc tgcattaatg aatcggccaa 4740
cgcgcgggga gaggcggttt gcgtattggg cgccagggtg gtttttcttt tcaccagtga 4800
gacgggcaac agctgattgc ccttcaccgc ctggccctga gagagttgca gcaagcggtc 4860
cacgctggtt tgccccagca ggcgaaaatc ctgtttgatg gtggttaacg gcgggatata 4920
acatgagctg tcttcggtat cgtcgtatcc cactaccgag atatccgcac caacgcgcag 4980
cccggactcg gtaatggcgc gcattgcgcc cagcgccatc tgatcgttgg caaccagcat 5040
cgcagtggga acgatgccct cattcagcat ttgcatggtt tgttgaaaac cggacatggc 5100
actccagtcg ccttcccgtt ccgctatcgg ctgaatttga ttgcgagtga gatatttatg 5160
ccagccagcc agacgcagac gcgccgagac agaacttaat gggcccgcta acagcgcgat 5220
ttgctggtga cccaatgcga ccagatgctc cacgcccagt cgcgtaccgt cttcatggga 5280
gaaaataata ctgttgatgg gtgtctggtc agagacatca agaaataacg ccggaacatt 5340
agtgcaggca gcttccacag caatggcatc ctggtcatcc agcggatagt taatgatcag 5400
cccactgacg cgttgcgcga gaagattgtg caccgccgct ttacaggctt cgacgccgct 5460
tcgttctacc atcgacacca ccacgctggc acccagttga tcggcgcgag atttaatcgc 5520
cgcgacaatt tgcgacggcg cgtgcagggc cagactggag gtggcaacgc caatcagcaa 5580
cgactgtttg cccgccagtt gttgtgccac gcggttggga atgtaattca gctccgccat 5640
cgccgcttcc actttttccc gcgttttcgc agaaacgtgg ctggcctggt tcaccacgcg 5700
ggaaacggtc tgataagaga caccggcata ctctgcgaca tcgtataacg ttactggttt 5760
cacattcacc accctgaatt gactctcttc cgggcgctat catgccatac cgcgaaaggt 5820
tttgcgccat tcgatggtgt ccgggatctc gacgctctcc cttatgcgac tcctgcatta 5880
ggaagcagcc cagtagtagg ttgaggccgt tgagcaccgc cgccgcaagg aatggtgcat 5940
gcaaggagat ggcgcccaac agtcccccgg ccacggggcc tgccaccata cccacgccga 6000
aacaagcgct catgagcccg aagtggcgag cccgatcttc cccatcggtg atgtcggcga 6060
tataggcgcc agcaaccgca cctgtggcgc cggtgatgcc ggccacgatg cgtccggcgt 6120
agaggatcga 6130
<210> 107
<211> 6114
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 107
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat ggcagccaca 120
catgaacact ctgcccaatg gctgaacaac tacaaaaaag gctacggtta tggcccttac 180
cctctgggca ttaacggtgg catgcactac ggcgttgact tttttatgaa catcggcacc 240
cctgtgaaag ccattagctc aggcaaaatc gtggaagccg gttggtcaaa ctatggcggt 300
ggcaaccaga tcggtctgat cgagaacgat ggtgtgcacc gccaatggta catgcacctg 360
tccaaataca acgttaaagt tggtgactac gtgaaagcag gccagattat cggctggtca 420
ggttcaaccg gttattcaac agcccctcat ctgcacttcc aacgcatggt gaatagtttt 480
agtaattcta ccgctcaaga tccgatgcca ttcctgaaat ctgccggtta tggtgagctg 540
agctccgtcg tcgtcgccgt cggcgtcgtc gttaaggatc cggctgctaa caaagcccga 600
aaggaagctg agttggctgc tgccaccgct gagcaataac tagcataacc ccttggggcc 660
tctaaacggg tcttgagggg ttttttgctg aaaggaggaa ctatatccgg atatcccgca 720
agaggcccgg cagtaccggc ataaccaagc ctatgcctac agcatccagg gtgacggtgc 780
cgaggatgac gatgagcgca ttgttagatt tcatacacgg tgcctgactg cgttagcaat 840
ttaactgtga taaactaccg cattaaagct agcttatcga tgataagctg tcaaacatga 900
gaattaattc ttgaagacga aagggcctcg tgatacgcct atttttatag gttaatgtca 960
tgataataat ggtttcttag acgtcaggtg gcacttttcg gggaaatgtg cgcggaaccc 1020
ctatttgttt atttttctaa atacattcaa atatgtatcc gctcatgaga caataaccct 1080
gataaatgct tcaataatat tgaaaaagga agagtatgag tattcaacat ttccgtgtcg 1140
cccttattcc cttttttgcg gcattttgcc ttcctgtttt tgctcaccca gaaacgctgg 1200
tgaaagtaaa agatgctgaa gatcagttgg gtgcacgagt gggttacatc gaactggatc 1260
tcaacagcgg taagatcctt gagagttttc gccccgaaga acgttttcca atgatgagca 1320
cttttaaagt tctgctatgt ggcgcggtat tatcccgtgt tgacgccggg caagagcaac 1380
tcggtcgccg catacactat tctcagaatg acttggttga gtactcacca gtcacagaaa 1440
agcatcttac ggatggcatg acagtaagag aattatgcag tgctgccata accatgagtg 1500
ataacactgc ggccaactta cttctgacaa cgatcggagg accgaaggag ctaaccgctt 1560
ttttgcacaa catgggggat catgtaactc gccttgatcg ttgggaaccg gagctgaatg 1620
aagccatacc aaacgacgag cgtgacacca cgatgcctgc agcaatggca acaacgttgc 1680
gcaaactatt aactggcgaa ctacttactc tagcttcccg gcaacaatta atagactgga 1740
tggaggcgga taaagttgca ggaccacttc tgcgctcggc ccttccggct ggctggttta 1800
ttgctgataa atctggagcc ggtgagcgtg ggtctcgcgg tatcattgca gcactggggc 1860
cagatggtaa gccctcccgt atcgtagtta tctacacgac ggggagtcag gcaactatgg 1920
atgaacgaaa tagacagatc gctgagatag gtgcctcact gattaagcat tggtaactgt 1980
cagaccaagt ttactcatat atactttaga ttgatttaaa acttcatttt taatttaaaa 2040
ggatctaggt gaagatcctt tttgataatc tcatgaccaa aatcccttaa cgtgagtttt 2100
cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga gatccttttt 2160
ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg gtggtttgtt 2220
tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc agagcgcaga 2280
taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag aactctgtag 2340
caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc agtggcgata 2400
agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg cagcggtcgg 2460
gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac accgaactga 2520
gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga aaggcggaca 2580
ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt ccagggggaa 2640
acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag cgtcgatttt 2700
tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg gcctttttac 2760
ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta tcccctgatt 2820
ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc agccgaacga 2880
ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg tattttctcc 2940
ttacgcatct gtgcggtatt tcacaccgca atggtgcact ctcagtacaa tctgctctga 3000
tgccgcatag ttaagccagt atacactccg ctatcgctac gtgactgggt catggctgcg 3060
ccccgacacc cgccaacacc cgctgacgcg ccctgacggg cttgtctgct cccggcatcc 3120
gcttacagac aagctgtgac cgtctccggg agctgcatgt gtcagaggtt ttcaccgtca 3180
tcaccgaaac gcgcgaggca gctgcggtaa agctcatcag cgtggtcgtg aagcgattca 3240
cagatgtctg cctgttcatc cgcgtccagc tcgttgagtt tctccagaag cgttaatgtc 3300
tggcttctga taaagcgggc catgttaagg gcggtttttt cctgtttggt cactgatgcc 3360
tccgtgtaag ggggatttct gttcatgggg gtaatgatac cgatgaaacg agagaggatg 3420
ctcacgatac gggttactga tgatgaacat gcccggttac tggaacgttg tgagggtaaa 3480
caactggcgg tatggatgcg gcgggaccag agaaaaatca ctcagggtca atgccagcgc 3540
ttcgttaata cagatgtagg tgttccacag ggtagccagc agcatcctgc gatgcagatc 3600
cggaacataa tggtgcaggg cgctgacttc cgcgtttcca gactttacga aacacggaaa 3660
ccgaagacca ttcatgttgt tgctcaggtc gcagacgttt tgcagcagca gtcgcttcac 3720
gttcgctcgc gtatcggtga ttcattctgc taaccagtaa ggcaaccccg ccagcctagc 3780
cgggtcctca acgacaggag cacgatcatg cgcacccgtg gccaggaccc aacgctgccc 3840
gagatgcgcc gcgtgcggct gctggagatg gcggacgcga tggatatgtt ctgccaaggg 3900
ttggtttgcg cattcacagt tctccgcaag aattgattgg ctccaattct tggagtggtg 3960
aatccgttag cgaggtgccg ccggcttcca ttcaggtcga ggtggcccgg ctccatgcac 4020
cgcgacgcaa cgcggggagg cagacaaggt atagggcggc gcctacaatc catgccaacc 4080
cgttccatgt gctcgccgag gcggcataaa tcgccgtgac gatcagcggt ccaatgatcg 4140
aagttaggct ggtaagagcc gcgagcgatc cttgaagctg tccctgatgg tcgtcatcta 4200
cctgcctgga cagcatggcc tgcaacgcgg gcatcccgat gccgccggaa gcgagaagaa 4260
tcataatggg gaaggccatc cagcctcgcg tcgcgaacgc cagcaagacg tagcccagcg 4320
cgtcggccgc catgccggcg ataatggcct gcttctcgcc gaaacgtttg gtggcgggac 4380
cagtgacgaa ggcttgagcg agggcgtgca agattccgaa taccgcaagc gacaggccga 4440
tcatcgtcgc gctccagcga aagcggtcct cgccgaaaat gacccagagc gctgccggca 4500
cctgtcctac gagttgcatg ataaagaaga cagtcataag tgcggcgacg atagtcatgc 4560
cccgcgccca ccggaaggag ctgactgggt tgaaggctct caagggcatc ggtcgagatc 4620
ccggtgccta atgagtgagc taacttacat taattgcgtt gcgctcactg cccgctttcc 4680
agtcgggaaa cctgtcgtgc cagctgcatt aatgaatcgg ccaacgcgcg gggagaggcg 4740
gtttgcgtat tgggcgccag ggtggttttt cttttcacca gtgagacggg caacagctga 4800
ttgcccttca ccgcctggcc ctgagagagt tgcagcaagc ggtccacgct ggtttgcccc 4860
agcaggcgaa aatcctgttt gatggtggtt aacggcggga tataacatga gctgtcttcg 4920
gtatcgtcgt atcccactac cgagatatcc gcaccaacgc gcagcccgga ctcggtaatg 4980
gcgcgcattg cgcccagcgc catctgatcg ttggcaacca gcatcgcagt gggaacgatg 5040
ccctcattca gcatttgcat ggtttgttga aaaccggaca tggcactcca gtcgccttcc 5100
cgttccgcta tcggctgaat ttgattgcga gtgagatatt tatgccagcc agccagacgc 5160
agacgcgccg agacagaact taatgggccc gctaacagcg cgatttgctg gtgacccaat 5220
gcgaccagat gctccacgcc cagtcgcgta ccgtcttcat gggagaaaat aatactgttg 5280
atgggtgtct ggtcagagac atcaagaaat aacgccggaa cattagtgca ggcagcttcc 5340
acagcaatgg catcctggtc atccagcgga tagttaatga tcagcccact gacgcgttgc 5400
gcgagaagat tgtgcaccgc cgctttacag gcttcgacgc cgcttcgttc taccatcgac 5460
accaccacgc tggcacccag ttgatcggcg cgagatttaa tcgccgcgac aatttgcgac 5520
ggcgcgtgca gggccagact ggaggtggca acgccaatca gcaacgactg tttgcccgcc 5580
agttgttgtg ccacgcggtt gggaatgtaa ttcagctccg ccatcgccgc ttccactttt 5640
tcccgcgttt tcgcagaaac gtggctggcc tggttcacca cgcgggaaac ggtctgataa 5700
gagacaccgg catactctgc gacatcgtat aacgttactg gtttcacatt caccaccctg 5760
aattgactct cttccgggcg ctatcatgcc ataccgcgaa aggttttgcg ccattcgatg 5820
gtgtccggga tctcgacgct ctcccttatg cgactcctgc attaggaagc agcccagtag 5880
taggttgagg ccgttgagca ccgccgccgc aaggaatggt gcatgcaagg agatggcgcc 5940
caacagtccc ccggccacgg ggcctgccac catacccacg ccgaaacaag cgctcatgag 6000
cccgaagtgg cgagcccgat cttccccatc ggtgatgtcg gcgatatagg cgccagcaac 6060
cgcacctgtg gcgccggtga tgccggccac gatgcgtccg gcgtagagga tcga 6114
<210> 108
<211> 6126
<212> DNA
<213> 人工的（Artificial）
<220>
<221> misc_feature
<223> 载体构建体
<400> 108
gatctcgatc ccgcgaaatt aatacgactc actatagggg aattgtgagc ggataacaat 60
tcccctctag aaataatttt gtttaaactt taagaaggag atatacatat ggcagccaca 120
catgaacact ctgcccaatg gctgaacaac tacaaaaaag gctacggtta tggcccttac 180
cctctgggca ttaacggtgg catgcactac ggcgttgact tttttatgaa catcggcacc 240
cctgtgaaag ccattagctc aggcaaaatc gtggaagccg gttggtcaaa ctatggcggt 300
ggcaaccaga tcggtctgat cgagaacgat ggtgtgcacc gccaatggta catgcacctg 360
tccaaataca acgttaaagt tggtgactac gtgaaagcag gccagattat cggctggtca 420
ggttcaaccg gttattcaac agcccctcat ctgcacttcc aacgcatggt gaatagtttt 480
agtaattcta ccgctcaaga tccgatgcca ttcctgaaat ctgccggtta tggtgagctg 540
agctcggtcg taaaaaacgt cgtcagcgtc gtcgtccgcc tcagtaagga tccggctgct 600
aacaaagccc gaaaggaagc tgagttggct gctgccaccg ctgagcaata actagcataa 660
ccccttgggg cctctaaacg ggtcttgagg ggttttttgc tgaaaggagg aactatatcc 720
ggatatcccg caagaggccc ggcagtaccg gcataaccaa gcctatgcct acagcatcca 780
gggtgacggt gccgaggatg acgatgagcg cattgttaga tttcatacac ggtgcctgac 840
tgcgttagca atttaactgt gataaactac cgcattaaag ctagcttatc gatgataagc 900
tgtcaaacat gagaattaat tcttgaagac gaaagggcct cgtgatacgc ctatttttat 960
aggttaatgt catgataata atggtttctt agacgtcagg tggcactttt cggggaaatg 1020
tgcgcggaac ccctatttgt ttatttttct aaatacattc aaatatgtat ccgctcatga 1080
gacaataacc ctgataaatg cttcaataat attgaaaaag gaagagtatg agtattcaac 1140
atttccgtgt cgcccttatt cccttttttg cggcattttg ccttcctgtt tttgctcacc 1200
cagaaacgct ggtgaaagta aaagatgctg aagatcagtt gggtgcacga gtgggttaca 1260
tcgaactgga tctcaacagc ggtaagatcc ttgagagttt tcgccccgaa gaacgttttc 1320
caatgatgag cacttttaaa gttctgctat gtggcgcggt attatcccgt gttgacgccg 1380
ggcaagagca actcggtcgc cgcatacact attctcagaa tgacttggtt gagtactcac 1440
cagtcacaga aaagcatctt acggatggca tgacagtaag agaattatgc agtgctgcca 1500
taaccatgag tgataacact gcggccaact tacttctgac aacgatcgga ggaccgaagg 1560
agctaaccgc ttttttgcac aacatggggg atcatgtaac tcgccttgat cgttgggaac 1620
cggagctgaa tgaagccata ccaaacgacg agcgtgacac cacgatgcct gcagcaatgg 1680
caacaacgtt gcgcaaacta ttaactggcg aactacttac tctagcttcc cggcaacaat 1740
taatagactg gatggaggcg gataaagttg caggaccact tctgcgctcg gcccttccgg 1800
ctggctggtt tattgctgat aaatctggag ccggtgagcg tgggtctcgc ggtatcattg 1860
cagcactggg gccagatggt aagccctccc gtatcgtagt tatctacacg acggggagtc 1920
aggcaactat ggatgaacga aatagacaga tcgctgagat aggtgcctca ctgattaagc 1980
attggtaact gtcagaccaa gtttactcat atatacttta gattgattta aaacttcatt 2040
tttaatttaa aaggatctag gtgaagatcc tttttgataa tctcatgacc aaaatccctt 2100
aacgtgagtt ttcgttccac tgagcgtcag accccgtaga aaagatcaaa ggatcttctt 2160
gagatccttt ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag 2220
cggtggtttg tttgccggat caagagctac caactctttt tccgaaggta actggcttca 2280
gcagagcgca gataccaaat actgtccttc tagtgtagcc gtagttaggc caccacttca 2340
agaactctgt agcaccgcct acatacctcg ctctgctaat cctgttacca gtggctgctg 2400
ccagtggcga taagtcgtgt cttaccgggt tggactcaag acgatagtta ccggataagg 2460
cgcagcggtc gggctgaacg gggggttcgt gcacacagcc cagcttggag cgaacgacct 2520
acaccgaact gagataccta cagcgtgagc tatgagaaag cgccacgctt cccgaaggga 2580
gaaaggcgga caggtatccg gtaagcggca gggtcggaac aggagagcgc acgagggagc 2640
ttccaggggg aaacgcctgg tatctttata gtcctgtcgg gtttcgccac ctctgacttg 2700
agcgtcgatt tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac gccagcaacg 2760
cggccttttt acggttcctg gccttttgct ggccttttgc tcacatgttc tttcctgcgt 2820
tatcccctga ttctgtggat aaccgtatta ccgcctttga gtgagctgat accgctcgcc 2880
gcagccgaac gaccgagcgc agcgagtcag tgagcgagga agcggaagag cgcctgatgc 2940
ggtattttct ccttacgcat ctgtgcggta tttcacaccg caatggtgca ctctcagtac 3000
aatctgctct gatgccgcat agttaagcca gtatacactc cgctatcgct acgtgactgg 3060
gtcatggctg cgccccgaca cccgccaaca cccgctgacg cgccctgacg ggcttgtctg 3120
ctcccggcat ccgcttacag acaagctgtg accgtctccg ggagctgcat gtgtcagagg 3180
ttttcaccgt catcaccgaa acgcgcgagg cagctgcggt aaagctcatc agcgtggtcg 3240
tgaagcgatt cacagatgtc tgcctgttca tccgcgtcca gctcgttgag tttctccaga 3300
agcgttaatg tctggcttct gataaagcgg gccatgttaa gggcggtttt ttcctgtttg 3360
gtcactgatg cctccgtgta agggggattt ctgttcatgg gggtaatgat accgatgaaa 3420
cgagagagga tgctcacgat acgggttact gatgatgaac atgcccggtt actggaacgt 3480
tgtgagggta aacaactggc ggtatggatg cggcgggacc agagaaaaat cactcagggt 3540
caatgccagc gcttcgttaa tacagatgta ggtgttccac agggtagcca gcagcatcct 3600
gcgatgcaga tccggaacat aatggtgcag ggcgctgact tccgcgtttc cagactttac 3660
gaaacacgga aaccgaagac cattcatgtt gttgctcagg tcgcagacgt tttgcagcag 3720
cagtcgcttc acgttcgctc gcgtatcggt gattcattct gctaaccagt aaggcaaccc 3780
cgccagccta gccgggtcct caacgacagg agcacgatca tgcgcacccg tggccaggac 3840
ccaacgctgc ccgagatgcg ccgcgtgcgg ctgctggaga tggcggacgc gatggatatg 3900
ttctgccaag ggttggtttg cgcattcaca gttctccgca agaattgatt ggctccaatt 3960
cttggagtgg tgaatccgtt agcgaggtgc cgccggcttc cattcaggtc gaggtggccc 4020
ggctccatgc accgcgacgc aacgcgggga ggcagacaag gtatagggcg gcgcctacaa 4080
tccatgccaa cccgttccat gtgctcgccg aggcggcata aatcgccgtg acgatcagcg 4140
gtccaatgat cgaagttagg ctggtaagag ccgcgagcga tccttgaagc tgtccctgat 4200
ggtcgtcatc tacctgcctg gacagcatgg cctgcaacgc gggcatcccg atgccgccgg 4260
aagcgagaag aatcataatg gggaaggcca tccagcctcg cgtcgcgaac gccagcaaga 4320
cgtagcccag cgcgtcggcc gccatgccgg cgataatggc ctgcttctcg ccgaaacgtt 4380
tggtggcggg accagtgacg aaggcttgag cgagggcgtg caagattccg aataccgcaa 4440
gcgacaggcc gatcatcgtc gcgctccagc gaaagcggtc ctcgccgaaa atgacccaga 4500
gcgctgccgg cacctgtcct acgagttgca tgataaagaa gacagtcata agtgcggcga 4560
cgatagtcat gccccgcgcc caccggaagg agctgactgg gttgaaggct ctcaagggca 4620
tcggtcgaga tcccggtgcc taatgagtga gctaacttac attaattgcg ttgcgctcac 4680
tgcccgcttt ccagtcggga aacctgtcgt gccagctgca ttaatgaatc ggccaacgcg 4740
cggggagagg cggtttgcgt attgggcgcc agggtggttt ttcttttcac cagtgagacg 4800
ggcaacagct gattgccctt caccgcctgg ccctgagaga gttgcagcaa gcggtccacg 4860
ctggtttgcc ccagcaggcg aaaatcctgt ttgatggtgg ttaacggcgg gatataacat 4920
gagctgtctt cggtatcgtc gtatcccact accgagatat ccgcaccaac gcgcagcccg 4980
gactcggtaa tggcgcgcat tgcgcccagc gccatctgat cgttggcaac cagcatcgca 5040
gtgggaacga tgccctcatt cagcatttgc atggtttgtt gaaaaccgga catggcactc 5100
cagtcgcctt cccgttccgc tatcggctga atttgattgc gagtgagata tttatgccag 5160
ccagccagac gcagacgcgc cgagacagaa cttaatgggc ccgctaacag cgcgatttgc 5220
tggtgaccca atgcgaccag atgctccacg cccagtcgcg taccgtcttc atgggagaaa 5280
ataatactgt tgatgggtgt ctggtcagag acatcaagaa ataacgccgg aacattagtg 5340
caggcagctt ccacagcaat ggcatcctgg tcatccagcg gatagttaat gatcagccca 5400
ctgacgcgtt gcgcgagaag attgtgcacc gccgctttac aggcttcgac gccgcttcgt 5460
tctaccatcg acaccaccac gctggcaccc agttgatcgg cgcgagattt aatcgccgcg 5520
acaatttgcg acggcgcgtg cagggccaga ctggaggtgg caacgccaat cagcaacgac 5580
tgtttgcccg ccagttgttg tgccacgcgg ttgggaatgt aattcagctc cgccatcgcc 5640
gcttccactt tttcccgcgt tttcgcagaa acgtggctgg cctggttcac cacgcgggaa 5700
acggtctgat aagagacacc ggcatactct gcgacatcgt ataacgttac tggtttcaca 5760
ttcaccaccc tgaattgact ctcttccggg cgctatcatg ccataccgcg aaaggttttg 5820
cgccattcga tggtgtccgg gatctcgacg ctctccctta tgcgactcct gcattaggaa 5880
gcagcccagt agtaggttga ggccgttgag caccgccgcc gcaaggaatg gtgcatgcaa 5940
ggagatggcg cccaacagtc ccccggccac ggggcctgcc accataccca cgccgaaaca 6000
agcgctcatg agcccgaagt ggcgagcccg atcttcccca tcggtgatgt cggcgatata 6060
ggcgccagca accgcacctg tggcgccggt gatgccggcc acgatgcgtc cggcgtagag 6120
gatcga 6126

Claims (10)

1.有效量的碱化剂和有效量的杀菌剂在制备用于治疗需要其的受试者中的细菌感染的药物中的用途，其中所述杀菌剂是细菌溶素或自溶素、或噬菌体溶素。
2.根据权利要求1所述的用途，其中所述细菌感染是胞内细菌感染或持留细菌感染，并且是葡萄球菌(Staphylococcus)感染。
3.根据权利要求2所述的用途，其中所述葡萄球菌感染是金黄色葡萄球菌(Staphylococcus.aureus)感染。
4.根据权利要求1所述的用途，其中宿主细胞是需要治疗的受试者内的真核宿主细胞且胞内区室是吞噬溶酶体。
5.根据权利要求1所述的用途，其中所述碱化剂选自氯喹、巴菲洛霉素A1和氯化铵的组。
6.根据权利要求1所述的用途，其中所述杀菌剂进一步包含蛋白转导结构域。
7.根据权利要求1所述的用途，其中所述杀菌剂进一步包含抗微生物肽。
8.根据权利要求6所述的用途，其中所述蛋白转导结构域选自由SEQ ID NO:12-25组成的组。
9.根据权利要求7所述的用途，其中所述抗微生物肽选自由SEQ ID NO:70-90组成的组。
10.根据权利要求1所述的用途，其中所述杀菌剂包含嵌合杀菌多肽，所述嵌合杀菌多肽与选自由SEQ ID NO:27-47组成的组中的序列具有至少40％的序列一致性，或者所述杀菌剂是由与选自由SEQ ID NO:50-67组成的组中的序列具有至少40％序列一致性的多核苷酸序列编码。
CN201680026953.2A 2015-03-12 2016-03-10 用于治疗细菌感染的杀菌剂与亲溶酶体碱化剂的组合 Active CN107580503B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP15158880 2015-03-12
EP15158880.3 2015-03-12
PCT/EP2016/055076 WO2016142445A2 (en) 2015-03-12 2016-03-10 A method of treatment of a bacterial infection

Publications (2)

Publication Number Publication Date
CN107580503A CN107580503A (zh) 2018-01-12
CN107580503B true CN107580503B (zh) 2021-07-09

Family

ID=52648929

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201680026953.2A Active CN107580503B (zh) 2015-03-12 2016-03-10 用于治疗细菌感染的杀菌剂与亲溶酶体碱化剂的组合

Country Status (12)

Country Link
US (1) US11690899B2 (zh)
EP (1) EP3268023B1 (zh)
JP (1) JP2018509415A (zh)
KR (1) KR20170132201A (zh)
CN (1) CN107580503B (zh)
AU (1) AU2016231141B2 (zh)
BR (1) BR112017019413A2 (zh)
CA (1) CA2979873A1 (zh)
HK (1) HK1249033A1 (zh)
IL (1) IL254457B (zh)
SG (1) SG11201707345VA (zh)
WO (1) WO2016142445A2 (zh)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3044121A1 (en) * 2016-11-18 2018-05-24 Lysando Ag New antimicrobial agents against staphylococcus aureus
ES2941467T3 (es) 2017-10-06 2023-05-23 Micreos Human Health Bv Tratamiento de una enfermedad asociada a la infección por una bacteria oncogénica
WO2019084343A1 (en) * 2017-10-25 2019-05-02 The Administrators Of The Tulane Educational Fund PEPTIDE COMPOSITIONS AND METHODS OF USE THEREOF
US11149068B2 (en) 2018-01-05 2021-10-19 The Administrator Of The Tulane Educational Fund Pore-forming peptides and uses thereof
JP7131803B2 (ja) * 2018-05-15 2022-09-06 学校法人大阪医科薬科大学 Ｇｂ３蓄積起因性疾患の予防又は治療剤
CN109350618B (zh) * 2018-12-10 2021-09-28 山东农业大学 自噬调节剂在消除牛乳腺上皮细胞内金黄色葡萄球菌中的应用
GB201906653D0 (en) * 2019-05-10 2019-06-26 Cc Biotech Ltd Polypeptides for treatment of bacterial infections
CA3171721A1 (en) 2020-03-19 2021-09-23 Fritz Eichenseher A stabilized protein of interest
WO2024020533A1 (en) * 2022-07-22 2024-01-25 Endolytix Technology, Inc. Immunogenic compositions for treating or preventing actinomycetia infections

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100028334A1 (en) * 2006-12-15 2010-02-04 Trustees Of Boston University Compositions and methods to potentiate colistin activity
US20130302306A1 (en) * 2012-05-09 2013-11-14 Raymond Schuch Bacteriophage lysin and antibiotic combinations against gram positive bacteria

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2001259205A1 (en) * 2000-04-28 2001-11-12 New Horizons Diagnostic Corporation The use of bacterial phage associated lysing enzymes for treating various illnesses
US20040023897A1 (en) * 2001-11-13 2004-02-05 Caplan Michael J. Methods for preventing or treating disease mediated by toxin-secreting bacteria
KR100759988B1 (ko) * 2006-08-04 2007-09-19 주식회사 인트론바이오테크놀로지 황색포도상구균에 특이적인 항균 단백질
US8383102B2 (en) 2009-05-21 2013-02-26 The United States Of America As Represented By The Secretary Of Agriculture Fusion of peptidoglycan hydrolase enzymes to a protein transduction domain allows eradication of both extracellular and intracellular gram positive pathogens
CA2772001A1 (en) 2009-08-24 2011-03-03 Katholieke Universiteit Leuven, K.U. Leuven R&D New endolysin obpgplys
EP2338916A1 (en) 2009-12-23 2011-06-29 Hyglos Invest GmbH Chimeric polypeptides and their use in bacterial decoloniation
EP2993181A1 (en) 2011-04-27 2016-03-09 Lysando AG New antimicrobial agents
US9382298B2 (en) * 2011-05-04 2016-07-05 Micreos Human Health B.V. Polypeptide
AU2013260249A1 (en) * 2012-05-07 2014-11-27 Micreos Human Health B.V. Polypeptide mixes with antibacterial activity
US9603909B2 (en) * 2012-05-29 2017-03-28 Intron Biotechnology, Inc. Composition capable of improving stability of bacteriophage lysin proteins
US9206411B2 (en) * 2012-06-13 2015-12-08 The United States Of America, As Represented By The Secretary Of Agriculture Staphylococcal Phage2638A endolysin amidase domain is lytic for Staphylococcus aureus
EP2679677A1 (en) 2012-06-29 2014-01-01 Lysando Aktiengesellschaft Composition for use in Mycobacteria therapy
US20160097044A1 (en) 2014-10-01 2016-04-07 The United States Of America, As Represented By The Secretary Of Agriculture Antimicrobial Enzyme Fusions Reduce Resistance and Kill Intracellular Staphylococcus aureus

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100028334A1 (en) * 2006-12-15 2010-02-04 Trustees Of Boston University Compositions and methods to potentiate colistin activity
US20130302306A1 (en) * 2012-05-09 2013-11-14 Raymond Schuch Bacteriophage lysin and antibiotic combinations against gram positive bacteria

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Factors influencing the intracellular activity of fluoroquinolones:a study using levofloxacin in a Staphylococcus aureus THP-1 monocyte model;Nguyen,et al;《Journal of Antimicrobial Chemotherapy》;20060313;第57卷;第883-890页 *
The availability of drugs: what does it mean in Ugandan primary care;J.Jitta,et al;《Health Policy》;20031231;第65卷;第167-179页 *
Use of Aminoglycosides in Treatment of Infections Due to Intracellular Bacteria;M.MAURIN,et al;《ANTIMICROBIAL AGENTS AND CHEMOTHERAPY》;20011130;第45卷(第11期);第2977-2986页 *

Also Published As

Publication number Publication date
SG11201707345VA (en) 2017-10-30
KR20170132201A (ko) 2017-12-01
CA2979873A1 (en) 2016-09-15
IL254457A0 (en) 2017-11-30
CN107580503A (zh) 2018-01-12
BR112017019413A2 (pt) 2018-05-02
AU2016231141B2 (en) 2022-03-03
EP3268023A2 (en) 2018-01-17
US11690899B2 (en) 2023-07-04
WO2016142445A3 (en) 2016-11-10
IL254457B (en) 2020-03-31
EP3268023B1 (en) 2021-08-18
US20180271952A1 (en) 2018-09-27
AU2016231141A1 (en) 2017-09-28
WO2016142445A2 (en) 2016-09-15
JP2018509415A (ja) 2018-04-05
HK1249033A1 (zh) 2018-10-26

Similar Documents

Publication Publication Date Title
CN107580503B (zh) 用于治疗细菌感染的杀菌剂与亲溶酶体碱化剂的组合
KR102451510B1 (ko) Pd-1 호밍 엔도뉴클레아제 변이체, 조성물 및 사용 방법
DK2768848T3 (en) METHODS AND PROCEDURES FOR EXPRESSION AND SECRETARY OF PEPTIDES AND PROTEINS
KR20170108946A (ko) Fc 수용체-유사 5를 표적화하는 키메라 항원 수용체 및 그의 용도
KR102654180B1 (ko) 프롤린 및 알라닌 잔기가 풍부한 반복적인 아미노산 서열을 암호화하고 낮은 반복적인 뉴클레오티드 서열을 갖는 핵산
KR102604096B1 (ko) 윌슨병을 치료하기 위한 유전자 치료
KR20210149060A (ko) Tn7-유사 트랜스포존을 사용한 rna-유도된 dna 통합
CN108753824A (zh) 用于治疗视网膜营养不良的病毒载体
CN101802006A (zh) 展示结合剂
KR20190100200A (ko) 동종이형 종양 세포 백신
CN112041334A (zh) 人foxp3在经基因编辑的t细胞中的表达
CN112912112A (zh) 肝特异性核酸调节元件以及其方法及用途
KR20230062873A (ko) 염기 편집 효소
CN116083398B (zh) 分离的Cas13蛋白及其应用
KR102409420B1 (ko) 형질전환 생물체 선별용 마커 조성물, 형질전환 생물체 및 형질전환 방법
KR20220142502A (ko) 근육 특이적 핵산 조절 요소 및 이의 방법 및 용도
US20030059870A1 (en) Recombinant bacterial strains for the production of natural nucleosides and modified analogues thereof
CN107988259B (zh) SmartBac杆状病毒表达系统及其应用
CN114990157B (zh) 用于构建lmna基因突变的扩张型心肌病模型猪核移植供体细胞的基因编辑系统及其应用
CN112063669A (zh) 酶法反应组合物、增加酶法反应中三磷酸腺苷(atp)量的方法及其应用
RU2779747C2 (ru) Химерные антигенные рецепторы, нацеленные на подобный fc-рецептору белок 5, и их применение
RU2781083C2 (ru) Варианты, композиции и методы применения хоминг-эндонуклеазы pd-1
KR20230123115A (ko) Ace-2 변이체 및 이의 용도
TW201030146A (en) High-expression promoter and method for producing gene product using the same
KR20220037964A (ko) 재조합 발생이 최소화된 유전자치료 벡터, 상기 벡터를 포함하는 재조합 레트로바이러스 및 상기 재조합 레트로바이러스를 포함하는 암의 예방 또는 치료용 약학 조성물

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