DELTA-(L-ALPHA-AMINOADIPYL)-L-CYSTEINYL-D-VALINE SYNTHETASE, THE MULTIENZYME INTEGRATING THE 4 PRIMARY REACTIONS IN BETA-LACTAM BIOSYNTHESIS, AS A MODEL PEPTIDE SYNTHETASE

ACV synthetase forms the tripeptide precursor of penicillins and cephalosporins from alpha-aminoadipate, cysteine, and valine. Catalytic sites for substrate carboxyl activation as adenylates, peptide bond formations, epimerization and release of the tripeptide-thioester are integrated in multifunctional enzymes of 405 to 425 kD. These have been characterized from several pro- and eukaryotic beta-lactam producers. Implications of these results for the thio-template mechanism of peptide formation are discussed, as well as the use of this multienzyme as a model system for enzymatic peptide synthesis.