Synthesis of (3S,5R)-carbapenam-3-carboxylic acid and its role in carbapenem biosynthesis and the stereoinversion problem.
(5R)-Carbapenem-3-carboxylic acid is the simplest structurally among the naturally occurring carbapenem beta-lactam antibiotics. It is the produced from (3S,5S)-carbapenam-3-carboxylic acid utilizing a remarkable stereoinversion/desaturation process by CarC (carbapenem synthase), an alpha-ketoglutarate dependent non-heme iron oxygenase. In this communication, we demonstrate for the first time that the epimeric (3S,5R)-carbapenam-3-carboxylic acid is an intermediate in the overall catalytic cycle to the carbapenem antibiotic. The role of alpha-ketoglutarate in the stereoinversion and desaturation processes is also examined.
Stapon
Anthony
A
Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Li
Rongfeng
R
Townsend
Craig A
CA
D015780:Carbapenems / Q000096:biosynthesis*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D007769:Lactams / Q000138:chemical synthesis / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016973:Pectobacterium carotovorum / Q000201:enzymology / Q000235:genetics; D013237:Stereoisomerism
D015780:Carbapenems; D007769:Lactams; C057567:carbapenam-3-carboxylic acid; D010088:Oxidoreductases; C022398:phytoene dehydrogenase