Bioconversion of Milbemycin-related Compounds: Biosynthetic Pathway of Milbemycins

• Published in: Journal of antibiotics Vol. 52; no. 2; pp. 109 - 116
• Main Authors: NONAKA, KOICHI, KUMASAKA, CHIEKO, OKAMOTO, YOSHIHIRO, MARUYAMA, FUMIO, YOSHIKAWA, HIROJI
• Format: Journal Article
• Language: English
• Published: TOKYO JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1999; JAPAN ANTIBIOT RES ASSN; Japan Antibiotics Research Association
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - metabolism; Antibiotics (antibacterial agents, antifungal agents); Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Applied microbiology; Biological and medical sciences; Biotechnology & Applied Microbiology; Biotransformation; Chromatography, High Pressure Liquid; Fermentation; Fundamental and applied biological sciences. Psychology; Immunology; Insecticides - chemistry; Insecticides - metabolism; Life Sciences & Biomedicine; Macrolides; Medical sciences; Microbiology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Streptomyces - genetics; Streptomyces - metabolism; Streptomyces hygroscopicus; FERMENTATION; MACROLIDE ANTIBIOTICS; AVERMECTIN BIOSYNTHESIS; STREPTOMYCES-AVERMITILIS; FAMILY; Actinomycetales; Streptomyces hygroscopicus; Antibiotic; Antifungal agent; Streptomycetaceae; Biotransformation; Microorganism culture; Bacteria; Actinomycetes; Biosynthesis; Fermentation; In vitro
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.52.109

Streptomyces hygroscopicus subsp. aureolacrimosus SANK 60286 and SANK 60576 produce many kinds of milbemycins. Among them, milbemycin α11, α14, A3, and A4 have the most effective acaricidal activity. In this study, we investigated the terminal biosynthetic pathway to milbemycin α14 and A4 which accumulated as the final products in these strains. Using cerulenin, a specific inhibitor of fatty acid and polyketide biosynthesis, we conducted bioconversion experiments with cultures of several mutants, including milbemycin A4- and α14-producing strains. The byconversions of milbemycin β6 to milbemycin A4 and milbemycin A4 to milbemycin α14 could be identified. For the biosynthesis of milbemycin A4 from milbemycin β6 in the milbemycin A4-high producing strain, there appeared to be two separate pathways exhibiting different sequences of furan ring formation and C-5 keto reduction steps.