Bioconversion and biosynthesis of 16-membered macrolide antibiotics. XXII. Biosynthesis of tylosin after protylonolide formation.

In order to clarify the later stages of tylosin biosynthesis, the biotransformation of tylosin-related compounds to tylosin was examined in a tylosin-producing strain, Streptomyces fradiae KA-427, with the aid of cerulenin, which is an inhibitor of fatty acid and polyketide biosynthesis. Protylonolide (9), 5-O-mycaminosylprotylonolide (11), deepoxycirramycin A1 (12), 20-deoxy-5-O-mycaminosylrelonolide (13), 5-O-mycaminosyltylonolide (3) and demycarosyltylosin (2) were bioconverted to tylosin. However, 23-hydroxyprotylonolide (10), 20-deoxydemycarosylrelomycin (14) and 20-deoxy-23-O-mycinosylrelonolide (16) were bioconverted not to tylosin, but to 20-deoxyrelomycin (15). Thus, the biosynthetic pathway via compounds 11 and 3 is proposed.