Identification and characterisation of shunt metabolites from isopenicillin N synthase

Abstract

Incubation of [(5S)-5-amino-5-carboxypentanoyl]-L-[3-¹³C]cysteinyl-D-[¹⁵N,3-²H]valine with isopenicillin N synthase (IPNS) resulted in the observation of a ‘shunt metabolite’, which we believe is formed from the collapse of an enzyme-bound monocyclic β-lactam intermediate, and which from chemical studies has been shown not to be derived from the decomposition of a free thiol monocyclic β-lactam.