δ-(L-α-Aminoadipyl)-L-Cysteinyl-D-Valine Synthetase, the Multienzyme Integrating the Four Primary Reactions in β-Lactam Biosynthesis, as a Model Peptide Synthetase

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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.