New fluorinated erythromycins obtained by mutasynthesis.
Following the previously described semisynthetic preparation of new aglycones (8S)-8-fluoroerythronolide A (I), (8S)-8-fluoroerythronolide B (II) and the monoglycoside 3-O-mycarosyl-(8S)-8-fluoroerythronolide B (III), their conversion into new fluoroerythromycins was attempted by mutational biosynthesis. The strain Streptomyces erythraeus ATCC 31772, a mutant blocked in the biosynthesis of erythromycin, was employed in the present investigation. Four new antibiotics, (8S)-8-fluoroerythromycin A (IV), (8S)-8-fluoroerythromycin B (V), (8S)-8-fluoroerythromycin C (VI) and (8S)-8-fluoroerythromycin D (VII) were successfully derived by such an approach. The result is also discussed in terms of the substrate specificity of the enzymes involved in the biosynthesis of erythromycins. The new antibiotics exhibited promising biological properties.
D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000633:toxicity; D005459:Fluorides; D008826:Microbial Sensitivity Tests; D009154:Mutation; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004917:Erythromycin; D005459:Fluorides