Title:
METHOD FOR LATE INTRODUCTION OF THE (8R)-HYDROXYL GROUP IN CARBAPENEM BETA-LACTAM ANTIBIOTIC SYNTHESIS
Document Type and Number:
WIPO Patent Application WO/2011/072287
Kind Code:
A3
Abstract:
The presently disclosed subject matter demonstrates that ThnG and ThnQ enzymes encoded by the thienamycin gene cluster in Streptomyces cattleya oxidize the C-2 and C-6 moieties of carbapenems, respectively. ThnQ stereospecifically hydroxylates PS-5 giving N-acetyl thienamycin. ThnG catalyzes sequential desaturation and sulfoxidation of PS-5, giving PS-7 and its sulfoxide. The ThnG and ThnQ enzymes are relatively substrate selective, but give rise to the oxidative diversity of carbapenems produced by S. cattleya, and orthologues likely function similarly in allied streptomyces.
Inventors:
TOWNSEND CRAIG ARTHUR (US)
BODNER MICAH JEFFREY (US)
PHELAN RYAN MARTIN (US)
FREEMAN MICHAEL FRANCIS (US)
BODNER MICAH JEFFREY (US)
PHELAN RYAN MARTIN (US)
FREEMAN MICHAEL FRANCIS (US)
Application Number:
PCT/US2010/060081
Publication Date:
November 10, 2011
Filing Date:
December 13, 2010
Export Citation:
Assignee:
UNIV JOHNS HOPKINS (US)
TOWNSEND CRAIG ARTHUR (US)
BODNER MICAH JEFFREY (US)
PHELAN RYAN MARTIN (US)
FREEMAN MICHAEL FRANCIS (US)
TOWNSEND CRAIG ARTHUR (US)
BODNER MICAH JEFFREY (US)
PHELAN RYAN MARTIN (US)
FREEMAN MICHAEL FRANCIS (US)
International Classes:
C07D477/20; A61K31/407; A61P31/00; C12P17/18
Foreign References:
| US20040038250A1 | 2004-02-26 | |||
| US4235922A | 1980-11-25 | |||
| US4374144A | 1983-02-15 |
Other References:
See also references of EP 2513112A4
Attorney, Agent or Firm:
CHILDERS, Jeffrey, W. (5th FloorBaltimore, MD, US)
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