Inhibition of penicillin biosynthesis by δ-(L-α-amino-δ-adipyl)-L-cysteinylglycine. Evidence for initial β-lactam ring formation

Abstract

Incubation of the modified substrate, δ-(L-α-amino-δ-adipyl)-L-cysteinylglycine (ACG) with the enzyme isopenicillin N synthetase resulted in inhibition at a rate which paralleled the rate of release of tritium (as ³HOH) from the [3-³H]cysteinyl isotopomer of ACG, while incubation of the [U-¹⁴C]cysteinyl isotopomer of ACG with the enzyme, in the presence of NaB³H₄, gave rise to ³H-labelled ACG, in which the tritium was shown to reside at the 3-cysteinyl position; these results are in accord with β-lactam formation during enzymic transformation of this substrate.