Biosynthesis of Carbapenem Antibiotics

Little has been published on the biosynthesis of the carbapenem antibiotics. Albers-Schonberg et al. 281) reported that the carbapenem nucleus in thienamycin is derived from glutamate and acetate as shown in Fig. 6, but so far no detailed account of this work has been published. Box 

Fukagawa et al. (282) presented evidence that the OA-6129 group of carbapenems, which possess the pantothenyl side-chain, could be early precursors of the carbapenem antibiotics. These compoimds were produced by a blocked mutant of Streptomyces fulvoviridis which lacked an acylase. This enzyme (A933 acylase) was isolated from the parent culture and was found to be able to remove the pantothenyl side-chain from the OA-6129 antibiotics  

The A933 acylase could also transacylate the OA-6129 antibiotics with acyl CoA derivatives and acylate the free amino compounds. 

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Fukagawa, Y, K. Kubo, K. Okamura, andT. Ishikawa Biosynthesis of Carbapenem Antibiotics. In Trends in Antibiotic Research (H. Umezawa, A. Demain,T. Hata, and C. Hutchinson, eds.). Japanese Antibiotics Research Association, Tokyo. 1982. 

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