Enzymatic conversion of the unnatural tripeptide delta-(D-alpha-aminoadipyl)-L-cysteinyl-D-valine to beta-lactam antibiotics.
Incubation of the unnatural tripeptide delta-(D-alpha-aminoadipyl)-L-cysteinyl-D-valine (DLD-ACV) with a partially purified extract of Cephalosporium acremonium resulted in the production of deacetoxycephalosporin C. The extract contained isopenicillin N synthetase (cyclase) and deacetoxycephalosporin C synthetase (expandase) but no penicillin epimerase activity, and was incubated aerobically in the presence of the components of the cyclase and expandase reaction mixtures (Fe++, ascorbate, dithiothreitol, alpha-ketoglutarate and ATP). The reaction was sensitive to penicillinase, indicating penicillin N to be an intermediate. However, when ring expansion was prevented by omission of alpha-ketoglutarate and ATP, no penicillin N was detected.
D000164:Acremonium / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D004798:Enzymes / Q000032:analysis; D019751:Intramolecular Transferases; D007535:Isomerases / Q000032:analysis; D009842:Oligopeptides / Q000378:metabolism*; D010088:Oxidoreductases; D046915:Penicillin-Binding Proteins; D010405:Penicillinase / Q000494:pharmacology; D010406:Penicillins / Q000096:biosynthesis; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D004798:Enzymes; D009842:Oligopeptides; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D047090:beta-Lactams; C011638:5-(2-aminoadipyl)cysteinylvaline; D010088:Oxidoreductases; C038370:isopenicillin N synthetase; D010405:Penicillinase; D007535:Isomerases; D019751:Intramolecular Transferases; C038371:deacetoxycephalosporin C synthetase; C006414:penicillin N