EP 1218486 A4 20021104 - IMPROVEMENT OF CLAVULANIC ACID PRODUCTION

Title (en)

IMPROVEMENT OF CLAVULANIC ACID PRODUCTION

Title (de)

VERBESSERUNG DER CLAVULANSäUREHERSTELLUNG

Title (fr)

PRODUCTION AMELIOREE D'ACIDE CLAVULANIQUE

Publication

EP 1218486 A4 20021104 (EN)

Application

EP 00970455 A 20000915

Priority

US 0025186 W 20000915
US 15421399 P 19990916

Abstract (en)

[origin: WO0119959A1] The invention methods for the enhancement of clavulanic acid production. In particular, the invention provides a method for increasing the production of clavulanic acid by: gene dosage with orf2 from the clavulanic acid biosynthetic pathway in Streptomyces clavuligerus; and by manipulation of fermentation conditions, especially the concentration of DG3P, a substrate of N2(carboxyethyl)arginine synthase, the protein encoded by orf2. A method for preparing N2(carboxyethyl)arginine synthase is also provided, as is an assay for identifying its substrates.

IPC 1-7

C12N 1/20; C12N 15/00; C12N 15/06; C12N 15/09; C12N 15/16; C12N 15/63; C12N 15/70; C12N 15/74; C07H 21/02; C07H 21/04

IPC 8 full level

C12N 15/06 (2006.01); C12N 15/16 (2006.01); C12N 15/76 (2006.01); C12P 17/18 (2006.01)

CPC (source: EP)

C12N 15/76 (2013.01); C12P 17/188 (2013.01)

Citation (search report)

[XD] CA 2108113 A1 19950409 - UNIV ALBERTA [CA]
[A] ES 2131001 A1 19990701 - ANTIBIOTICOS SAU [ES]
[A] EP 0349121 A2 19900103 - BEECHAM GROUP PLC [GB]
[A] WO 9833896 A2 19980806 - SMITHKLINE BEECHAM PLC [GB], et al
[PX] PEREZ-REDONDO ROSARIO ET AL: "Deletion of the pyc gene blocks clavulanic acid biosynthesis except in glycerol-containing medium: Evidence for two different genes in formation of the C3 unit.", JOURNAL OF BACTERIOLOGY, vol. 181, no. 22, November 1999 (1999-11-01), pages 6922 - 6928, XP002216538, ISSN: 0021-9193
[PX] JENSEN SUSAN E ET AL: "Enzymes catalyzing the early steps of clavulanic acid biosynthesis are encoded by two sets of paralogous genes in Streptomyces clavuligerus.", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY., vol. 44, no. 3, March 2000 (2000-03-01), pages 720 - 726, XP002216539, ISSN: 0066-4804
[X] ROMERO J ET AL: "utilization of ornithine and arginine as specific precursors of clavulanic acid by S. clavuligerus", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, WASHINGTON,DC, US, vol. 52, no. 4, 1 October 1986 (1986-10-01), pages 892 - 897, XP002083075, ISSN: 0099-2240
[X] IVES PAUL R ET AL: "Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus.", MICROBIOLOGY (READING), vol. 143, no. 11, November 1997 (1997-11-01), pages 3573 - 3579, XP002216540, ISSN: 1350-0872
[X] JENSEN S E ET AL: "BIOSYNTHESIS AND MOLECULAR GENETICS OF CLAVULANIC ACID", ANTONIE VAN LEEUWENHOEK, DORDRECHT, NL, vol. 75, 1999, pages 125 - 133, XP000937780
[AD] MCNAUGHTON H J ET AL: "BETA-LACTAM SYNTHETASE: IMPLICATIONS FOR BETA-LACTAMASE EVOLUTION", CHEMICAL COMMUNICATIONS, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 21, 1998, pages 2325 - 2326, XP002900777, ISSN: 1359-7345
[AD] TOWNSEND C A ET AL: "BIOSYNTHESIS OF CLAVULANIC-ACID ORIGIN OF THE 3-CARBON UNIT", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 107, no. 4, 1985, pages 1066 - 1068, XP001106978, ISSN: 0002-7863
[AD] PITLIK, J.; TOWNSEND, C. A.: "The fate of [2,3,3-2H3, 1,2-13C2]-D, L-glycerate in clavulanic acid biosynthesis", CHEMICAL COMMUNICATIONS, vol. 2, 1997, pages 225 - 226, XP001107210
[AD] TOWNSEND C A ET AL: "BIOSYNTHESIS OF CLAVULANIC-ACID ORIGIN OF THE 5 CARBON UNIT", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 107, no. 4, 1985, pages 1065 - 1066, XP001117431, ISSN: 0002-7863
See references of WO 0119959A1

Designated contracting state (EPC)

AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

DOCDB simple family (publication)

WO 0119959 A1 20010322; AU 7983400 A 20010417; EP 1218486 A1 20020703; EP 1218486 A4 20021104; HK 1047957 A1 20030314

DOCDB simple family (application)

US 0025186 W 20000915; AU 7983400 A 20000915; EP 00970455 A 20000915; HK 02109461 A 20021231