JPH09503908A - 3‐(カルボキシエチルチオ)プロピオニル‐7‐adcaを経由した7‐adcaの効果的な製造法 - Google Patents
3‐(カルボキシエチルチオ)プロピオニル‐7‐adcaを経由した7‐adcaの効果的な製造法Info
- Publication number
- JPH09503908A JPH09503908A JP7505584A JP50558495A JPH09503908A JP H09503908 A JPH09503908 A JP H09503908A JP 7505584 A JP7505584 A JP 7505584A JP 50558495 A JP50558495 A JP 50558495A JP H09503908 A JPH09503908 A JP H09503908A
- Authority
- JP
- Japan
- Prior art keywords
- adca
- gene
- carboxyethylthio
- propionyl
- enzyme
- 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
Links
Classifications
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- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- 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.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/14—Fungi; Culture media therefor
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- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
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- 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)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
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- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Botany (AREA)
- Virology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Steroid Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.下記の工程を含む、7-アミノデスアセトキシセファロスポラニック酸(7-ADC A)の製造及び回収方法: a)ペニシリウム・クリソゲナム菌株を、拡大酵素遺伝子で、糸状菌発現シグ ナルの転写及び翻訳調節下で、形質転換する工程; b)前記菌株を培養培地内で発酵し、かつその場で拡大され、3-(カルボキシ エチルチオ)プロピオニル-7-ADCAを形成するような、3-(カルボキシエチルチ オ)プロピオニル-6-アミノペニシラン酸(3-(カルボキシエチルチオ)プロピ オニル-6-APA)を得るのに適している、3,3'-チオジプロピオン酸もしくはその 塩又はエステルを、該培養培地に添加する工程; c)該発酵ブロスから、3-(カルボキシエチルチオ)プロピオニル-7-ADCAを 回収する工程; d)前記3-(カルボキシエチルチオ)プロピオニル-7-ADCAを、脱アシル化す る工程;及び e)この結晶性7-ADCAを回収する工程である。 2.前記ペニシリウム・クリソゲナム菌株が、該AT遺伝子の発現シグナルの転写 及び翻訳調節下において、拡大酵素遺伝子によって形質転換される、請求の範囲 第1項記載の方法。 3.前記工程(e)が、ろ過工程である、請求の範囲第1又は2項に記載の方法。 4.前記工程(c)がろ過工程であり、かつ該ブロスのろ液の、水と混和しない有 機溶媒による、約4.5より低いpHでの抽出、並びにこれの水によるpH4〜10の範囲 での逆抽出による、請求の範囲第1から3項のいずれか1項記載の方法。 5.前記拡大酵素遺伝子が、ストレプトミセス・クラブリゲラス又はノカルジア ・ラクタムデュランスに由来する、請求の範囲第1から4項のいずれか1項記載 の方法。 6.糸状菌発現シグナルの転写及び翻訳調節と機能的に連結した、拡大酵素をコ ードしているDNAを含む、組換えDNAベクター。 7.前記拡大酵素をコードしているDNAが、該AT遺伝子の発現シグナルの転写及 び翻訳調節と機能的に連結している、請求の範囲第6項記載の組換えDNAベク ター。 8.前記拡大酵素をコードしているDNAが、ストレプトミセス・クラブリゲラス 又はノカルジア・ラクタムデュランスに由来している、請求の範囲第6又は7項 記載の組換えDNAベクター。 9.請求の範囲第6、7又は8項のいずれか1項に記載されたベクターによって 形質転換された宿主細胞。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP93202260 | 1993-07-30 | ||
EP93203695 | 1993-12-24 | ||
NL93203695.7 | 1993-12-24 | ||
NL93202260.1 | 1993-12-24 | ||
PCT/EP1994/002544 WO1995004149A1 (en) | 1993-07-30 | 1994-07-29 | Process for the efficient production of 7-adca via 3-(carboxyethylthio)propionyl-7-adca |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH09503908A true JPH09503908A (ja) | 1997-04-22 |
JP3574453B2 JP3574453B2 (ja) | 2004-10-06 |
Family
ID=26133941
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP50558495A Expired - Fee Related JP3574453B2 (ja) | 1993-07-30 | 1994-07-29 | 3‐(カルボキシエチルチオ)プロピオニル‐7‐adcaを経由した7‐adcaの効果的な製造法 |
Country Status (17)
Country | Link |
---|---|
US (1) | US5795733A (ja) |
EP (1) | EP0711348B1 (ja) |
JP (1) | JP3574453B2 (ja) |
KR (1) | KR100327881B1 (ja) |
CN (1) | CN1087780C (ja) |
AT (1) | ATE234926T1 (ja) |
BR (1) | BR9407104A (ja) |
CA (1) | CA2168004A1 (ja) |
CZ (1) | CZ285622B6 (ja) |
DE (1) | DE69432303D1 (ja) |
ES (1) | ES2194873T3 (ja) |
HU (1) | HU219265B (ja) |
PL (1) | PL180565B1 (ja) |
PT (1) | PT711348E (ja) |
SI (1) | SI0711348T1 (ja) |
SK (1) | SK282617B6 (ja) |
WO (1) | WO1995004149A1 (ja) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6709859B1 (en) * | 1986-01-31 | 2004-03-23 | Beecham Group P.L.C. | Chromosomal DNA Fragments Encoding Enzymes for Encoding B-Lactam Biosynthesis Enzymes, and Vector and Transformants for Their Expression |
EP0233715B1 (en) * | 1986-01-31 | 1994-05-25 | BEECHAM GROUP plc | Isolation and expression of genes involved in the biosynthesis of beta-lactams |
US5731165A (en) * | 1995-06-02 | 1998-03-24 | Gist-Brocades, B.V. | Process for the production of 7-ADCA via expandase activity on penicillin G |
PL182509B1 (pl) * | 1995-06-02 | 2002-01-31 | Gist Brocades Bv | Sposób wytwarzania kwasu 7-aminodezacetoksycefalosporanowego (7-ADCA) |
US5919680A (en) * | 1995-11-27 | 1999-07-06 | Isis Innovation Limited | Process for the production of SSC's via expandase activity on penicillin G |
PL330760A1 (en) | 1997-04-22 | 1999-05-24 | Gist Brocades Bv | Method of obatining decylated cephalosporins by fermentation process |
ZA983394B (en) | 1997-04-22 | 1998-10-30 | Gist Brocades Bv | Process for the fermentative production of deacylated cephalosporins |
ID27054A (id) * | 1998-05-19 | 2001-02-22 | Dsm Nv | Perbaikan produksi sepalosporin di dalam organisme yang hidup |
US6455603B1 (en) | 1998-06-30 | 2002-09-24 | Dow Global Technologies Inc. | Polymer polyols and a process for the production thereof |
JP2002533092A (ja) * | 1998-12-22 | 2002-10-08 | デーエスエム・ナムローゼ・フェンノートシャップ | セファロスポリンの改良されたinvivo産生 |
EP2851423B1 (en) | 2005-12-28 | 2016-03-02 | DSM Sinochem Pharmaceuticals Netherlands B.V. | Mutant type II beta-lactam acylases |
EP2123772A1 (en) | 2008-04-29 | 2009-11-25 | DSM IP Assets B.V. | Beta-lactam antibiotic producing strains |
CN102131921A (zh) | 2008-08-05 | 2011-07-20 | 帝斯曼知识产权资产管理有限公司 | 生产己二酰基-7-adca的菌株 |
EP2310489A1 (en) * | 2008-08-05 | 2011-04-20 | DSM IP Assets B.V. | Adipoyl-7-adca producing strains |
WO2010115838A1 (en) | 2009-04-03 | 2010-10-14 | Dsm Ip Assets B.V. | Fermentation process |
HUE035540T2 (en) | 2010-06-22 | 2018-05-02 | Dsm Sinochem Pharm Nl Bv | Air bubble fermentation process |
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 |
EP2681224B1 (en) | 2011-03-03 | 2016-06-22 | DSM Sinochem Pharmaceuticals Netherlands B.V. | Degradation of penicillin compounds |
CN104093831A (zh) | 2012-01-31 | 2014-10-08 | 中化帝斯曼制药有限公司荷兰公司 | 半合成抗生素生产中的类MbtH蛋白 |
WO2015091455A1 (en) | 2013-12-17 | 2015-06-25 | Dpx Holdings B.V. | Bioreactor |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5070020A (en) * | 1988-05-09 | 1991-12-03 | Eli Lilly And Company | Recombinant dna expression vectors and dna compounds that encode deacetoxycephalosporin c synthetase |
US5082772A (en) * | 1988-10-24 | 1992-01-21 | Eli Lilly And Company | Process for preparing deacetylcephalosporin c |
US5318896A (en) * | 1991-09-11 | 1994-06-07 | Merck & Co., Inc. | Recombinant expandase bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid (7-ADCA) |
SK280569B6 (sk) * | 1991-10-15 | 2000-03-13 | Gist-Brocades B.V. | Biologický spôsob výroby kyseliny7-aminodeacetylce |
-
1994
- 1994-07-29 EP EP94926136A patent/EP0711348B1/en not_active Expired - Lifetime
- 1994-07-29 PL PL94312747A patent/PL180565B1/pl not_active IP Right Cessation
- 1994-07-29 PT PT94926136T patent/PT711348E/pt unknown
- 1994-07-29 JP JP50558495A patent/JP3574453B2/ja not_active Expired - Fee Related
- 1994-07-29 KR KR1019960700485A patent/KR100327881B1/ko not_active IP Right Cessation
- 1994-07-29 AT AT94926136T patent/ATE234926T1/de not_active IP Right Cessation
- 1994-07-29 CN CN94192932A patent/CN1087780C/zh not_active Expired - Fee Related
- 1994-07-29 WO PCT/EP1994/002544 patent/WO1995004149A1/en active IP Right Grant
- 1994-07-29 SI SI9430443T patent/SI0711348T1/xx unknown
- 1994-07-29 US US08/591,501 patent/US5795733A/en not_active Expired - Fee Related
- 1994-07-29 CZ CZ96157A patent/CZ285622B6/cs not_active IP Right Cessation
- 1994-07-29 DE DE69432303T patent/DE69432303D1/de not_active Expired - Lifetime
- 1994-07-29 CA CA002168004A patent/CA2168004A1/en not_active Abandoned
- 1994-07-29 BR BR9407104A patent/BR9407104A/pt not_active Application Discontinuation
- 1994-07-29 ES ES94926136T patent/ES2194873T3/es not_active Expired - Lifetime
- 1994-07-29 HU HU9600195A patent/HU219265B/hu not_active IP Right Cessation
- 1994-07-29 SK SK98-96A patent/SK282617B6/sk unknown
Also Published As
Publication number | Publication date |
---|---|
HU9600195D0 (en) | 1996-03-28 |
SI0711348T1 (en) | 2003-08-31 |
CN1128545A (zh) | 1996-08-07 |
HU219265B (en) | 2001-03-28 |
US5795733A (en) | 1998-08-18 |
EP0711348B1 (en) | 2003-03-19 |
CN1087780C (zh) | 2002-07-17 |
KR960704048A (ko) | 1996-08-31 |
BR9407104A (pt) | 1996-08-27 |
PT711348E (pt) | 2003-08-29 |
KR100327881B1 (ko) | 2002-07-02 |
SK282617B6 (sk) | 2002-10-08 |
JP3574453B2 (ja) | 2004-10-06 |
PL180565B1 (pl) | 2001-02-28 |
EP0711348A1 (en) | 1996-05-15 |
HUT75367A (en) | 1997-05-28 |
WO1995004149A1 (en) | 1995-02-09 |
PL312747A1 (en) | 1996-05-13 |
ATE234926T1 (de) | 2003-04-15 |
CZ15796A3 (en) | 1996-07-17 |
SK9896A3 (en) | 1996-09-04 |
ES2194873T3 (es) | 2003-12-01 |
CA2168004A1 (en) | 1995-02-09 |
CZ285622B6 (cs) | 1999-10-13 |
DE69432303D1 (de) | 2003-04-24 |
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