RU99101109A - The method of enzymatic production of deacylated cephalosporins - Google Patents
The method of enzymatic production of deacylated cephalosporinsInfo
- Publication number
- RU99101109A RU99101109A RU99101109/13A RU99101109A RU99101109A RU 99101109 A RU99101109 A RU 99101109A RU 99101109/13 A RU99101109/13 A RU 99101109/13A RU 99101109 A RU99101109 A RU 99101109A RU 99101109 A RU99101109 A RU 99101109A
- Authority
- RU
- Russia
- Prior art keywords
- cephalosporin
- acyl
- derivative
- side chain
- precursor
- Prior art date
Links
- 150000001780 cephalosporins Chemical class 0.000 title claims 7
- 230000002255 enzymatic Effects 0.000 title 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N precursor Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims 4
- 230000000813 microbial Effects 0.000 claims 3
- NVIAYEIXYQCDAN-CLZZGJSISA-N 7β-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 claims 2
- 108091022082 Acyl transferases Proteins 0.000 claims 2
- 102000019632 Acyl transferases Human genes 0.000 claims 2
- 229940049954 Penicillin Drugs 0.000 claims 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims 2
- 229960000626 benzylpenicillin Drugs 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 230000003234 polygenic Effects 0.000 claims 2
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7-ACA Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 claims 1
- 241000228431 Acremonium chrysogenum Species 0.000 claims 1
- 101710029063 CEFEF Proteins 0.000 claims 1
- 101700061430 SAT19 Proteins 0.000 claims 1
- 101700081234 TTR Proteins 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 101700034534 cefE Proteins 0.000 claims 1
- 230000000875 corresponding Effects 0.000 claims 1
- 238000005947 deacylation reaction Methods 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- 238000000855 fermentation Methods 0.000 claims 1
- 230000004151 fermentation Effects 0.000 claims 1
- 238000011065 in-situ storage Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- MNFORVFSTILPAW-UHFFFAOYSA-N Β-Lactam Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 claims 1
Claims (9)
ферментации микробного штамма, способного к продуцированию β-лактама и экспрессии ацилтрансферазы, а также экспандазной активности и, необязательно, ацетилтрансферазной и/или гидроксилазной активности, в присутствии предшественника боковой цепи формулы (1)
HOOC - X - COOH
где X представляет (CH2)m-CH=A-(CH2)n или (CH2)m-C≡C-(CH2)n, где m и n, каждый по отдельности, представляют 0, 1, 2 или 3, и m+n = 2 или 3, и А представляет CH или N,
или X представляет (CH2)p-CH=CH-CH=CH-(CH2)q, где р и q, каждый по отдельности, представляют 0 или 1, и p+q = 0 или 1,
или его соли, эфира или амида, причем указанный предшественник боковой цепи дает производное ацил-6-АРА, включающее указанный предшественник, причем указанное производное ацил-6-АРА in situ расширяется до соответствующего производного ацил-7-ADCA, и, необязательно, превращается затем в производное ацил-7-ADAC или ацил-7-ACA, и
извлечения производного ацил-7-цефалоспорина из ферментационного бульона,
деацилирования указанного производного ацил-7-цефалоспорина, и
извлечения кристаллического N-деацилированного цефалоспорина.1. The method of obtaining N-deacylated cephalosporin, which includes stages
fermenting a microbial strain capable of producing β-lactam and expressing an acyltransferase, as well as expanding activity and, optionally, acetyltransferase and / or hydroxylase activity, in the presence of a side chain precursor of formula (1)
HOOC - X - COOH
where X represents (CH 2 ) m —CH = A- (CH 2 ) n or (CH 2 ) m —C≡C- (CH 2 ) n , where m and n, each separately, represent 0, 1, 2 or 3, and m + n = 2 or 3, and A is CH or N,
or X is (CH 2 ) p -CH = CH-CH = CH- (CH 2 ) q , where p and q, each separately, represent 0 or 1, and p + q = 0 or 1,
or its salt, ester or amide, and the specified precursor of the side chain gives the derivative of acyl-6-APA, including the specified predecessor, and the specified derivative of acyl-6-APA in situ expands to the corresponding derivative of acyl-7-ADCA, and optionally turns then to an acyl-7-ADAC or acyl-7-ACA derivative, and
extracting the acyl-7-cephalosporin derivative from the fermentation broth,
deacylation of the acyl-7-cephalosporin derivative, and
extraction of crystalline N-deacylated cephalosporin.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97201197.7 | 1997-04-22 | ||
EP97201197 | 1997-04-22 |
Publications (2)
Publication Number | Publication Date |
---|---|
RU99101109A true RU99101109A (en) | 2000-11-20 |
RU2208643C2 RU2208643C2 (en) | 2003-07-20 |
Family
ID=8228237
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU99101109/13A RU2208643C2 (en) | 1997-04-22 | 1998-04-22 | Method for preparing n-deacylated cephalosporin |
Country Status (17)
Country | Link |
---|---|
US (1) | US6410259B1 (en) |
EP (1) | EP0915988B1 (en) |
JP (1) | JP2000512512A (en) |
KR (1) | KR20000022109A (en) |
CN (1) | CN1145703C (en) |
AT (1) | ATE231919T1 (en) |
AU (1) | AU7909498A (en) |
BR (1) | BR9804854A (en) |
DE (1) | DE69811039T2 (en) |
ES (1) | ES2191313T3 (en) |
ID (1) | ID21520A (en) |
PL (1) | PL330760A1 (en) |
PT (1) | PT915988E (en) |
RU (1) | RU2208643C2 (en) |
SI (1) | SI0915988T1 (en) |
WO (1) | WO1998048035A1 (en) |
ZA (1) | ZA983395B (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU3042600A (en) * | 1998-12-22 | 2000-07-12 | Dsm N.V. | Improved (in vivo) production of cephalosporins |
EP2123772A1 (en) | 2008-04-29 | 2009-11-25 | DSM IP Assets B.V. | Beta-lactam antibiotic producing strains |
EP2392649A3 (en) | 2008-08-05 | 2012-01-11 | DSM IP Assets B.V. | Adipoyl-7-ADCA producing strains |
WO2010015624A1 (en) | 2008-08-05 | 2010-02-11 | Dsm Ip Assets B.V. | Adipoyl-7-adca producing strains |
CN102369290A (en) | 2009-04-03 | 2012-03-07 | 帝斯曼知识产权资产管理有限公司 | Fermentation process |
CN103003439A (en) | 2010-06-22 | 2013-03-27 | 中化帝斯曼制药有限公司荷兰公司 | Air bubble fermentation process |
BR112013022521B1 (en) | 2011-03-03 | 2019-05-07 | Dsm Sinochem Pharmaceuticals Netherlands B.V. | Process for the degradation of a ß-lactamic compound and use of sulphite in the degradation of a ß-lactamic compound |
CN102757999A (en) * | 2011-04-29 | 2012-10-31 | 上海医药工业研究院 | Fermentation medium for production of 7-aminocephalosporanic acid and fermentation method of fermentation medium |
WO2015091455A1 (en) | 2013-12-17 | 2015-06-25 | Dpx Holdings B.V. | Bioreactor |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT83746B (en) | 1985-11-15 | 1988-08-17 | Gist Brocades Nv | PROCESS FOR THE PREPARATION OF NEW IMMOBILIZED BIOCATALYZERS AND FOR THE PRODUCTION OF ETHANOL BY FERMENTATION |
PT97116B (en) | 1990-03-23 | 1998-10-30 | Gist Brocades Nv | PROCESS FOR MODIFYING THE PRODUCTION OF SECONDARY METABOLITES, IN ADDITION TO BETA-LACTAMA DERIVATIVES |
US5318896A (en) * | 1991-09-11 | 1994-06-07 | Merck & Co., Inc. | Recombinant expandase bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid (7-ADCA) |
CZ288721B6 (en) * | 1991-10-15 | 2001-08-15 | Dsm Gist B. V. | Novel bioprocess for preparing 7-aminodeacetylcephalosporanic acid |
US5726032A (en) * | 1993-07-30 | 1998-03-10 | Gist-Brocades B.V. | Process for the efficient production of 7-ADCA via 2-(carboxyethylthio)acetyl-7-ADCA and 3-(carboxymethylthio)propionyl-7-ADCA |
JP3574453B2 (en) | 1993-07-30 | 2004-10-06 | ギスト ブロカデス ベスローテン フェンノートシャップ | Effective method for producing 7-ADCA via 3- (carboxyethylthio) propionyl-7-ADCA |
-
1998
- 1998-04-22 US US09/202,797 patent/US6410259B1/en not_active Expired - Fee Related
- 1998-04-22 PL PL98330760A patent/PL330760A1/en unknown
- 1998-04-22 AT AT98929264T patent/ATE231919T1/en not_active IP Right Cessation
- 1998-04-22 SI SI9830380T patent/SI0915988T1/en unknown
- 1998-04-22 ZA ZA983395A patent/ZA983395B/en unknown
- 1998-04-22 CN CNB988005247A patent/CN1145703C/en not_active Expired - Fee Related
- 1998-04-22 DE DE69811039T patent/DE69811039T2/en not_active Expired - Fee Related
- 1998-04-22 WO PCT/EP1998/002461 patent/WO1998048035A1/en not_active Application Discontinuation
- 1998-04-22 ES ES98929264T patent/ES2191313T3/en not_active Expired - Lifetime
- 1998-04-22 RU RU99101109/13A patent/RU2208643C2/en not_active IP Right Cessation
- 1998-04-22 JP JP10545046A patent/JP2000512512A/en active Pending
- 1998-04-22 EP EP98929264A patent/EP0915988B1/en not_active Expired - Lifetime
- 1998-04-22 PT PT98929264T patent/PT915988E/en unknown
- 1998-04-22 KR KR1019980710519A patent/KR20000022109A/en not_active Application Discontinuation
- 1998-04-22 AU AU79094/98A patent/AU7909498A/en not_active Abandoned
- 1998-04-22 ID IDW980130A patent/ID21520A/en unknown
- 1998-04-22 BR BR9804854-6A patent/BR9804854A/en not_active IP Right Cessation
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