Isopenicillin N synthetase signatures

Isopenicillin N synthetase (EC 1.21.3.1) (IPNS) [1,2] is a key enzyme in the biosynthesis of penicillin and cephalosporin. In the presence of oxygen, it removes iron and ascorbate, four hydrogen atoms from L-(α-aminoadipyl)-L-cysteinyl-d-valine to form the azetidinone and thiazolidine rings of isopenicillin. IPNS is an enzyme of about 330 amino-acid residues. 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 [3] 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) [4] also related to IPNS.

We derived two signature patterns for these enzymes, centered around the conserved cysteine residues.