Isopenicillin N synthase

[2] The ligation of ACV results in a decrease in the Fe(II)/Fe(III) redox potential, which facilitates the reduction of dioxygen to superoxide.

Formation of a highly covalent RS-Fe(III) bond[5][6] lowers the activation barrier to dioxygen binding, thereby initiating the reaction cycle.

[4] This causes the hydrogen atom at the C-3 of the valine residue to come closer to the iron(IV) oxo ligand which is highly electrophilic.

A second hydrogen transfer occurs, most likely producing an isopropyl radical which closes the thiazolidine ring by attacking the thiolate sulfur atom.

[1] This shows how IPNS occupies an early and key role in the biosynthetic pathway of all of the penicillins and cephalosporins, which are different types of β-lactam antibiotics.

Ribbon diagram of isopenicillin N Synthase. Active site iron is visible at center in gray. From PDB 1BK0
Close up rendering of active site of isopenicillin N synthase, showing His270, His214, Asp216 (top left to right, clockwise), and a water molecule coordinating the ferrous active site, while ACV (bottom right) binds. From PDB 1BK0
Pathway of penicillin and cephalosporin biosynthesis, illustrating the role of isopenicillin N synthase in the formation of beta-lactam antibiotics