Characterization of Kinetics and Products of the Baeyer−Villiger Oxygenase MtmOIV, The Key Enzyme of the Biosynthetic Pathway toward the Natural Product Anticancer Drug Mithramycin from <i>Streptomyces </i><i>a</i><i>rgillaceus</i>

Abstract

MtmOIV, the key oxygenase of the mithramycin biosynthetic pathway in Streptomyces argillaceus, was proven to act initially as Baeyer-Villiger monooxygenase, but may also catalyze various follow-up reaction steps. The reaction of the overexpressed pure His6-tagged enzyme with its substrate premithramycin B was studied. Various intermediates and products were isolated and physicochemically characterized, several of them being previously unknown compounds. This is the first example in which a bacterial enzyme was unequivocally proven to act as Baeyer-Villigerase with its natural substrate, that is, in its natural context.