A CYTOCHROME P450-LIKE GENE POSSIBLY INVOLVED IN OLEANDOMYCIN BIOSYNTHESIS BY STREPTOMYCES-ANTIBIOTICUS

A cosmid clone from an oleandomycin producer, Streptomyces antibioticu s, contains a large open reading frame encoding a type I polyketide sy nthase subunit and an oleandomycin resistance gene (oleB). Sequencing of a 1.4-kb DNA fragment adjacent to oleB revealed the existence of an open reading frame (oleP) encoding a protein similar to several cytoc hrome P450 monooxygenases from different sources, including the produc ts of the eryF and elyK genes from Saccharopolyspora erythraea that pa rticipate in erythromycin biosynthesis. The oleP gene was expressed in Escherichia coli as a fusion protein to a maltose-binding protein. Us ing polyclonal antibodies against this fusion protein it was observed that the synthesis of the cytochrome P450 was in parallel to that of o leandomycin. The cytochrome P450 encoded by the oleP gene could be res ponsible for the epoxidation of carbon 8 of the oleandomycin lactone r ing.