Biological conversion of erythronolide B, an intermediate of erythromycin biogenesis, into new "hybrid" macrolide antibiotics.
Transformation of erythronolide B to new antibiotics was attempted by feeding this compound during the fermentation of Streptomyces antibioticus ATCC31771, a blocked mutant of an oleandomycin producing strain. As a result, four new active compounds were obtained with hybrid structures between erythromycin and oleandomycin. They were identified as 3-O-oleandrosyl-5-O-desosaminyl-15-hydroxyerythronolide B (I), 3-O-oleandrosyl-5-O-desosaminylerythronolide B (II), 3-O-oleandrosyl-5-O-desosaminyl-(8S)-8-hydroxyerythronolide B (III) and 3-O-oleandrosyl-5-O-desosaminyl-(8R)-8,19-epoxyerythronolide B (IV). They were found to be less active, but more stable to acid, than erythromycin A. From their relative biogenetical relationship together with the structure elucidated some hypotheses about late stages of oleandomycin biosynthesis are inferred too.
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D004355:Drug Stability; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D005285:Fermentation; D013302:Streptomyces / Q000378:metabolism*; D013303:Streptomyces antibioticus / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; C038315:erythronolide B; D004917:Erythromycin