Structure of cytochrome P450eryF involved in erythromycin biosynthesis

Abstract

Cytochrome P450eryF catalyzes the 6S-hydroxylation of 6-deoxyerythronolide B, the initial reaction in a multistep pathway to convert 6-deoxyerythronolide B into the antibiotic, erythromycin. The overall structure of P450eryF is similar to that of P450cam but differs in the exact positioning of several alpha-helices. The largest difference occurs in the B' helix and results in the enlargement of the substrate-binding pocket of P450eryF. The substrate is positioned with the macrolide ring perpendicular to the haem plane and contacts seven hydrophobic residues and three solvent molecules. The substrate participates in a network of hydrogen bonds that may provide a proton shuttle pathway in the oxygen cleavage reaction.