Biosynthesis carbapenem antibiotic

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, 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. 

P-Lactams. AH 3-lactams are chemically characterized by having a 3-lactam ring. Substmcture groups are the penicillins, cephalosporias, carbapenems, monobactams, nocardicias, and clavulanic acid. Commercially this family is the most important group of antibiotics used to control bacterial infections. The 3-lactams act by inhibition of bacterial cell wall biosynthesis. 

Occurrence, Fermentation, and Biosynthesis. Although a large number of Streptomjces species have been shown to produce carbapenems, only S. cattkja (2) and S. penemfaciens (11) have been reported to give thienamycin (2). Generally the antibiotics occur as a mixture of analogues or isomers and are often co-produced with penicillin N and cephamycin C. Yields are low compared to other P-lactams produced by streptomycetes, and titres are of the order of 1—20 p-g sohdusmL despite, in many cases, a great deal of effort on the optimization of the media and fermentation conditions. The rather poor stabiUty of the compounds also contributes to a low recovery in the isolation procedures. The fermentation and isolation processes for thienamycin and the olivanic acids has been reviewed in some detail (12). 

Occurrence, Fermentation, and Biosynthesis. Although a large number of Streptomyces species have been shown to produce carbapenems. only S. cattleya and S. penemfaciens have been reported to give thienamycin. Generally the antibiotics occur as a mixture of analogues or isomers and are often coproduced with penicillin N and cephaniycin C. 

The synthesis of the carbapenam-3-carboxylic acid 36 <03JA15746> as well as a study on carbapenem biosynthesis have been documented <03JA8486>. The cephalosporin derivative 37 has been prepared and its use as a novel fluorogenic substrate for imaging P-lactamase gene expression demonstrated <03JA11146>. The nucleus of the carbacephem antibiotic loracarbef has been synthesized in a highly efficient and enantioselective fashion from 25,3iS-2-amino-3-hydroxy-6-heptenoic acid, which was derived from enzyme-catalyzed... 

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