ES2165276B1 - Procedimiento biotecnologico para la produccion de acido 7-aminocefal osporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc) - Google Patents
Procedimiento biotecnologico para la produccion de acido 7-aminocefal osporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc)Info
- Publication number
- ES2165276B1 ES2165276B1 ES009901365A ES9901365A ES2165276B1 ES 2165276 B1 ES2165276 B1 ES 2165276B1 ES 009901365 A ES009901365 A ES 009901365A ES 9901365 A ES9901365 A ES 9901365A ES 2165276 B1 ES2165276 B1 ES 2165276B1
- Authority
- ES
- Spain
- Prior art keywords
- chrysogenum
- daoc
- cefef
- cefe
- adca
- 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.)
- Expired - Fee Related
Links
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
Landscapes
- 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.
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) |
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) |
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) |
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 ES2165276A1 (es) | 2002-03-01 |
ES2165276B1 true 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 (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002316862A1 (en) * | 2001-04-19 | 2002-11-05 | Bioferma Murcia, S.A. | Enzymatic process for preparing cephalosporin derivatives |
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 |
CN115838753A (zh) * | 2021-09-18 | 2023-03-24 | 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 |
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 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5318896A (en) * | 1991-09-11 | 1994-06-07 | Merck & Co., Inc. | Recombinant expandase bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid (7-ADCA) |
KR100227711B1 (ko) * | 1991-10-15 | 1999-12-01 | 한스 발터 라벤 | 7-아미노세팔로스포란산 및 7-아미노데아세틸세팔로스포란산 제조를 위한 신규한 생물학적 공정 |
SK282624B6 (sk) * | 1993-07-30 | 2002-10-08 | Dsm N. V. | Spôsob výroby a izolácie 7-aminodesacetoxycefalosporánovej kyseliny |
US6368820B1 (en) * | 1996-07-16 | 2002-04-09 | Dsm N.V. | Process for the preparation of cephalosporins using acremonium chrysogenum |
-
1999
- 1999-06-18 ES ES009901365A patent/ES2165276B1/es not_active Expired - Fee Related
-
2000
- 2000-06-13 WO PCT/ES2000/000211 patent/WO2000078989A1/es not_active Application Discontinuation
- 2000-06-13 CN CN00809128A patent/CN1357051A/zh active Pending
- 2000-06-13 AU AU52231/00A patent/AU5223100A/en not_active Abandoned
- 2000-06-13 EP EP00936911A patent/EP1188838A1/en not_active Withdrawn
- 2000-06-13 KR KR1020017016020A patent/KR20020022701A/ko not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
KR20020022701A (ko) | 2002-03-27 |
AU5223100A (en) | 2001-01-09 |
EP1188838A1 (en) | 2002-03-20 |
WO2000078989A1 (es) | 2000-12-28 |
CN1357051A (zh) | 2002-07-03 |
ES2165276A1 (es) | 2002-03-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2165276B1 (es) | Procedimiento biotecnologico para la produccion de acido 7-aminocefal osporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc) | |
RU2178808C2 (ru) | Способ получения 7-аминодезацетоксицефалоспорановой кислоты (7-adca) | |
BR9910532A (pt) | Produção melhorada in vivo de cefalosporina | |
Sonawane | Enzymatic modifications of cephalosporins by cephalosporin acylase and other enzymes | |
RO116648B1 (ro) | Bioprocedeu pentru prepararea acidului 7-amino-3-deacetil-cefalosporanic si a acidului 7-aminocefalosporanic | |
WO1996005318A1 (en) | Mutated penicillin g acylase genes | |
DE69019967D1 (de) | Enzymatisches verfahren zur herstellung von 7-aminocephalosporansäure. | |
ES2395945T3 (es) | Expandasas mutantes | |
GB2323361A (en) | Improved process for the production of semi-synthetic cephalosporins via expandase activity on penicillin G | |
KR100469873B1 (ko) | 푸자리움 옥시스포룸으로부터의 페니실린v 아미도하이드롤라아제 유전자 | |
Hardianto et al. | Cephalosporin C acylase from microbes for one-step enzymatic transformation of cephalosporin C to 7-aminocephalosporanic acid | |
WO2007006593A2 (en) | Mutant expandases and their use in the production of beta-lactam compounds | |
Morgan et al. | Substrate specificity of recombinant Streptomyces clavuligerus deacetoxycephalosporin C synthase. | |
WO1998016648A3 (en) | Isopenicillin n synthetase and deacetoxycephalosporin c synthetase enzymes and methods | |
US7195892B2 (en) | Acylase gene | |
Pitkina | Perspectives on the use of metabolic engineering in beta-lactam antibiotic biosyntheses | |
Ghosh | Strategies for manipulation of genes in microbes for production of β-lactam antibiotics | |
RU2202616C2 (ru) | Способ получения 7-аминоцефалоспорановой кислоты, вектор экспрессии, рекомбинантный штамм | |
Sklyarenko et al. | Enzymatic transformation and synthesis of beta-lactam antibiotics | |
Baldwin et al. | Cleavage of the 5-amino-5-carboxy-2-oxapentanoyl side chain from enzymatically synthesised penicillins and cephalosporins | |
RU94022268A (ru) | Способы получения промежуточных продуктов для синтеза цефалоспориновых антибиотиков, векторы, клетка | |
PL172155B1 (pl) | Sposób biotechnologiczny wytwarzania pochodnych kwasu cefalosporanowego |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EC2A | Search report published |
Date of ref document: 20020301 Kind code of ref document: A1 Effective date: 20020301 |
|
FG2A | Definitive protection |
Ref document number: 2165276B1 Country of ref document: ES |
|
FD1A | Patent lapsed |
Effective date: 20100312 |