InterPro: IPR002057 Isopenicillin N synthase, conserved site

Isopenicillin N synthase (IPNS) is a nonhaem-Fe²⁺-dependent enzyme that belongs to a class of nonhaem Fe²⁺-containing enzymes, which includes 2-oxoglutarate-dependent dioxygenases, 2-oxoglutarate-dependent hydroxy- lases, and enzymes involved in ethylene formation and anthocyaninidin biosynthesis. IPNS catalyses the stereospecific formation of the beta-lactam and thiazolidine rings of IPN via a 4-electron oxidation of the tripeptide ACV. The enzyme uses, as the sole electron acceptor, one molecule of dioxygen, which is completely reduced to two molecules of water. The oxygen stoichiometry shown by IPNS is the same as that for cytochrome C oxidase, but is unusual for nonhaem-iron-containing enzymes, which typically catalyse the transfer of one or both atoms of dioxygen into their substrates. IPNS thus provides an interesting contrast to dioxygenase enzymes.

Two cysteines are conserved in fungal and bacterial IPNS sequences; these may be involved in iron-binding and/or substrate-binding.

Cephalosporium acremonium DAOCS/DACS [1] is a bifunctional enzyme involved in cephalosporin biosynthesis. The DAOCS domain, which is structurally related to IPNS, catalyzes the step from penicillin N to deacetoxy-cephalosporin C - used as a substrate by DACS to form deacetylcephalosporin C. Streptomyces clavuligerus possesses a monofunctional DAOCS enzyme (gene cefE) [2] also related to IPNS.