Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces coelicolor: mechanism and stereochemistry of the enzymatic formation of epi-isozizaene

A two-step, cytochrome P450-catalyzed oxidation of epi-isozizaene synthase from Streptomyces coelicolor to yield antibiotic albaflavenone as final product is reported. A site-directed mutagenesis of active site residues in two universally conserved [Mg.sup.2+]-binding domains and the identification of six minor sesquiterpene products produced by the wild-type and mutant proteins provide insight into the mechanism and the role of the enzyme epi-isozizaene synthase.