Production of the penicillin precursor δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine (ACV) by cell-free extracts fromStreptomyces clavuligerus

Glycerol-stabilised cell extracts of Streptomyces clavuligerus contain an enzyme activity which synthesises ACV from the individual amino acids l-α-aminoadipic acid, l-cysteine and l-valine. Enzyme activity was optimum in reaction mixtures containing 1 mM ATP together with an ATP regenerating system. The ACV synthetase enzyme formed ACV analogs when provided with l-carboxymethylcysteine in place of l-α-aminoadipic acid or when provided with l-alloisoleucine or l-α-aminobutyrate in place of l-valine. Multistep conversion of individual amino acids to penicillin and cephalosporin antibiotics was restricted as a result of the inhibitory effects of l-α-aminoadipic acid and l-cysteine on isopenicillin N synthetase.