Penicillin biosynthesis: the origin of hydroxy groups in β-lactams derived from unsaturated substrates

Abstract

Two unsaturated peptide substrates were each cyclised by the enzyme isopenicillin N synthase (IPNS) from Cephalosporium acremonium CO 728 simultaneously to both desaturated and hydroxylated β-lactam products whose hydroxy groups have been shown to derive their oxygen atom from the cosubstrate dioxygen; a working hypothesis involving iron–oxo species is proposed to explain this phenomenon.