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ES2165276A1 - Procedimiento biotecnologico para la produccion del acido 7-aminocefalosporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc) - Google Patents

Procedimiento biotecnologico para la produccion del acido 7-aminocefalosporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc)

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Publication number
ES2165276A1
ES2165276A1 ES009901365A ES9901365A ES2165276A1 ES 2165276 A1 ES2165276 A1 ES 2165276A1 ES 009901365 A ES009901365 A ES 009901365A ES 9901365 A ES9901365 A ES 9901365A ES 2165276 A1 ES2165276 A1 ES 2165276A1
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ES
Spain
Prior art keywords
chrysogenum
cefef
gene
daoc
cefe
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.)
Granted
Application number
ES009901365A
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English (en)
Other versions
ES2165276B1 (es
Inventor
Alvarez Javier Velasco
Fondevila Jose Adrio
Valle Miguel Angel Moreno
Garcia Bruno Diez
Morales Manuel Esteban
Ermanno Bernasconi
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.)
Antibioticos SA
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Antibioticos SA
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Publication date
Application filed by Antibioticos SA filed Critical Antibioticos SA
Priority to ES009901365A priority Critical patent/ES2165276B1/es
Priority to KR1020017016020A priority patent/KR20020022701A/ko
Priority to AU52231/00A priority patent/AU5223100A/en
Priority to EP00936911A priority patent/EP1188838A1/en
Priority to PCT/ES2000/000211 priority patent/WO2000078989A1/es
Priority to CN00809128A priority patent/CN1357051A/zh
Publication of ES2165276A1 publication Critical patent/ES2165276A1/es
Application granted granted Critical
Publication of ES2165276B1 publication Critical patent/ES2165276B1/es
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P35/00—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin
    • 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
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
    • C12N9/0014—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on the CH-NH2 group of donors (1.4)
    • C12N9/0022—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on the CH-NH2 group of donors (1.4) with oxygen as acceptor (1.4.3)
    • C12N9/0024—D-Amino acid oxidase (1.4.3.3)
    • 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)
    • C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/80—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P35/00—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin
    • C12P35/02—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin by desacylation of the substituent in the 7 position

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

Abstract

Procedimiento de obtención de ácido 7- aminodesacetoxicefalosporánico (7-ADCA). El procedimiento está basado en la utilización de desacetoxicefalosporina C (DAOC) producida directamente por fermentación de Acremonium chrysogenum (también denominado Cephalosporium acremonium) y catalizado por las actividades enzimáticas D-aminoácido oxidases (DAO) y glutaril-7-ACA acilasa (GLA). El método de producción de DAOC por fermentación de A. chrysogenum está basado en la inactivación del gen cefEF y posterior expresión del gen cefE dando lugar a la cepa A. chrysogenum {dl}cefEF-cefE. La invención incluye los siguientes apartados: (I) inactivación del gen cefEF de A. chrysogenum, el cual codifica para las actividades enzimáticas desacetoxicefalosporina C sintasa (DAOCS o expandasa) y desacetilcefalosporina C sintasa (DACS o hidroxilasa), (II) expresión del gen cefE, el cual codifica para la actividad enzimática DAOCS, procedente de un actinomiceto en el transformarte de A. chrysogenum inactivado en elgen cefEF, (III) desarrollo de un método de fermentación de la cepa recombinante para la producción de DAOC y (IV) conversión enzimática de DAOC en 7-ADCA catalizada por las enzimas DAO y GLA. Alternativamente, sería posible producir 7-ADCA directamente por fermentación de A. chrysogenum mediante la expresión conjunta de los genes que codifican para DAO y GLA en la cepa A. chrysogenum {dl}cefEF-cefE productora de DAOC o a través de la expresión de un gen que codifica para la enzima cefalosporina acilasa en A. chrysogenum {dl}cefEF-cefE.
ES009901365A 1999-06-18 1999-06-18 Procedimiento biotecnologico para la produccion de acido 7-aminocefal osporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc) Expired - Fee Related ES2165276B1 (es)

Priority Applications (6)

Application Number Priority Date Filing Date Title
ES009901365A ES2165276B1 (es) 1999-06-18 1999-06-18 Procedimiento biotecnologico para la produccion de acido 7-aminocefal osporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc)
KR1020017016020A KR20020022701A (ko) 1999-06-18 2000-06-13 7-아미노데스아세톡시세팔로스포란산의 제조 방법
AU52231/00A AU5223100A (en) 1999-06-18 2000-06-13 Method for producing 7-aminodesacetoxycephalosporanic acid (7-adca)
EP00936911A EP1188838A1 (en) 1999-06-18 2000-06-13 Method for producing 7-aminodesacetoxycephalosporanic acid (7-adca)
PCT/ES2000/000211 WO2000078989A1 (es) 1999-06-18 2000-06-13 Procedimiento de obtencion de acido 7-aminodes-acetoxicefalosporanico (7-adca)
CN00809128A CN1357051A (zh) 1999-06-18 2000-06-13 7－氨基去乙酰氧基头孢菌素酸(7－adca)的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES009901365A ES2165276B1 (es) 1999-06-18 1999-06-18 Procedimiento biotecnologico para la produccion de acido 7-aminocefal osporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc)

Publications (2)

Publication Number Publication Date
ES2165276A1 true ES2165276A1 (es) 2002-03-01
ES2165276B1 ES2165276B1 (es) 2003-03-01

Family

ID=8308899

Family Applications (1)

Application Number Title Priority Date Filing Date
ES009901365A Expired - Fee Related ES2165276B1 (es) 1999-06-18 1999-06-18 Procedimiento biotecnologico para la produccion de acido 7-aminocefal osporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc)

Country Status (6)

Country Link
EP (1) EP1188838A1 (es)
KR (1) KR20020022701A (es)
CN (1) CN1357051A (es)
AU (1) AU5223100A (es)
ES (1) ES2165276B1 (es)
WO (1) WO2000078989A1 (es)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040014499A (ko) * 2001-04-19 2004-02-14 바이오퍼마 무르시아, 에스.에이. α-케토산 유도체를 이용하여 3-세팔로스포란산 유도체를제조하는 방법
CN101654694B (zh) * 2008-08-22 2011-08-31 湖南福来格生物技术有限公司 一种3-去乙酰基-7-氨基头孢烯酸的制备方法
CN103108879B (zh) * 2010-09-07 2016-08-17 中化帝斯曼制药有限公司荷兰公司 用于生产头孢菌素类的方法
CN103436521A (zh) * 2013-06-28 2013-12-11 山东鲁抗医药股份有限公司 一种头孢菌素c高产菌株选育方法
CN103525796A (zh) * 2013-10-18 2014-01-22 江苏辉腾生物医药科技有限公司 具有戊二酰基-7-氨基头孢烷酸酰化酶和d-氨基酸氧化酶活性的重组酶及其制备方法和应用
CN107557348B (zh) * 2016-07-01 2022-07-08 百瑞全球有限公司 头孢菌素羟化酶突变体、编码该突变体的dna、使用该突变体的方法及其应用
CN108640931B (zh) * 2018-07-23 2020-03-24 华北制药股份有限公司 一种7-adca晶体及其制备方法
KR102194740B1 (ko) * 2019-09-18 2020-12-23 아미코젠주식회사 7-adca 제조를 위한 데아세트옥시세팔로스포린 c의 고농도 생산 재조합 아크레모니움 크리소제눔 균주의 제조방법 및 이 방법으로 제조된 균주
CN112852912B (zh) * 2020-04-10 2022-01-11 中国科学院天津工业生物技术研究所 一种合成7-氨基去乙酰氧基头孢烷酸的方法
CN112831421B (zh) * 2020-12-25 2023-03-03 伊犁川宁生物技术股份有限公司 一种头孢菌素类化合物生产菌株及其应用
CN113234092A (zh) * 2021-04-13 2021-08-10 伊犁川宁生物技术股份有限公司 一种头孢类中间体7-氨基3-去乙酰氧基头孢烷酸及其制备方法
CN113583877B (zh) * 2021-07-23 2024-01-09 伊犁川宁生物技术股份有限公司 一种发酵生产去乙酰氧基脱头孢烷酸的方法
CN113637024B (zh) * 2021-08-03 2024-01-09 伊犁川宁生物技术股份有限公司 一种去乙酰氧基头孢菌素c水溶液提纯的方法
CN115838753B (zh) * 2021-09-18 2024-10-29 中国科学院天津工业生物技术研究所 一种生产7-氨基去乙酰氧基头孢烷酸的方法
KR102688632B1 (ko) * 2022-10-26 2024-07-26 아미코젠주식회사 7-adca 제조를 위한 데아세톡시세팔로스포린 c의 고농도 및 고순도 생산 균주 및 이를 이용한 제조 방법
CN116656505B (zh) * 2023-04-23 2024-04-16 四川大学 一种高产醇脱氢酶和酰基转移酶菌株及培养方法及应用

Citations (3)

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WO1998002567A2 (en) * 1996-07-16 1998-01-22 Gist-Brocades B.V. PROCESS FOR THE PREPARATION OF CEPHALOSPORINS USING $i(ACREMONIUM CHRYSOGENUM)
EP0843013A2 (en) * 1991-09-11 1998-05-20 Gist-Brocades B.V. Novel bioprocess for preparing 7-ADCA
EP0856516A1 (en) * 1991-10-15 1998-08-05 Gist-Brocades B.V. Novel bioprocess for preparing 7-aca and 7-adac

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HU219259B (en) * 1993-07-30 2001-03-28 Gist Brocades Bv Process for the efficient production of 7-adca via 2-(carboxyethylthio)acetyl-7-adca and 3-(carboxymethylthio)propionyl-7-adca, recombinant dna vectrors and transformed host cells

Patent Citations (3)

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EP0843013A2 (en) * 1991-09-11 1998-05-20 Gist-Brocades B.V. Novel bioprocess for preparing 7-ADCA
EP0856516A1 (en) * 1991-10-15 1998-08-05 Gist-Brocades B.V. Novel bioprocess for preparing 7-aca and 7-adac
WO1998002567A2 (en) * 1996-07-16 1998-01-22 Gist-Brocades B.V. PROCESS FOR THE PREPARATION OF CEPHALOSPORINS USING $i(ACREMONIUM CHRYSOGENUM)

Non-Patent Citations (3)

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CRAWFORD L. ET AL.: 'Production of cephalosporin intermediates by feeding adipic acid to recombinant penicillium chrysogenum strains expressing ring expansion activity' BIOTECHNOLOGY vol. 13, 1995, pages 58 - 62, XP000606289 *
GHOSH P.K.: 'Strategies for manipulation of genes in microbes for production of B-lactam antibiotics' CURRENT SCIENCE vol. 76, no. 8, 1999, pages 1096 - 1107, XP000995734 *

Also Published As

Publication number Publication date
EP1188838A1 (en) 2002-03-20
WO2000078989A1 (es) 2000-12-28
CN1357051A (zh) 2002-07-03
ES2165276B1 (es) 2003-03-01
AU5223100A (en) 2001-01-09
KR20020022701A (ko) 2002-03-27

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