CLONING OF THE MACROLIDE ANTIBIOTIC BIOSYNTHESIS GENE ACYA, WHICH ENCODES 3-O-ACYLTRANSFERASE, FROM STREPTOMYCES THERMOTOLERANS AND ITS USEFOR DIRECT FERMENTATIVE PRODUCTION OF A HYBRID MACROLIDE ANTIBIOTIC

A gene encoding the macrolide modification enzyme 3-O-acyltransferase (acyA) was cloned by chromosome walking onto the carbomycin biosynthet ic region in Streptomyces thermotolerans TH475, with the 3' region of the gene encoding the macrolide modification enzyme 4''-O-acyltransfer ase (acyB1) as a probe. A shortened fragment (1.8 kb) containing acyA was subcloned with pIJ350. A high level tylosin producer, Streptomyces fradiae MBBF, transformed with the plasmid could produce a hybrid mac rolide, 3-O-acetyltylosin, most efficiently.