Stepwise ring closure in penicillin biosynthesis. Intitial β-lactam formation

Abstract

Incubation of a 1 : 1 mixture of δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (L,L,D-ACV) and L,L,D-A[3,3-²H₂]CV with a cell-free extract of isopenicillin N synthetase from Cephalosporium acremonium results in preferential conversion of the fully protiated substrate into isopenicillin N; alternatively a similar experiment with a 1 : 1 mixture of L,L,D-ACV and L,L,D-AC[3-²H]V gave isopenicillin N without isotopic discrimination between the two substrates.