Cephalosporin C biosynthesis; a branched pathway sensitive to a kinetic isotope effect

Abstract

Incubation of [3-²H] penicillin N with preparations of deacetoxycephalosporin C/deacetylcephalosporin C synthetase activity from Cephalosporium acremonium CO 728 gave, along with the normal product deacetoxycephalosporin C, another β-lactam metabolite namely 7β-[(R)-5-amino-5-carboxypentanoyl]-3β-hydroxy-3α-methyl[4-²H)-cepham-4α-carboxylic acid. This material arises as a result of a deuterium isotope effect on a branched pathway in the enzymic mechanism. The 3β-hydroxy group in this substance arises from molecular oxygen.