Bioconversion of AS1387392: bioconversion studies involving Amycolatopsis azurea JCM 3275

• Published in: Journal of antibiotics Vol. 63; no. 11; pp. 643 - 647
• Main Authors: Sasamura, Satoshi, Ohsumi, Keisuke, Takase, Shigehiro, Yamada, Toshiko, Muramatsu, Hideyuki, Fujie, Akihiko, Mori, Hiroaki, Fujii, Takashi, Hino, Motohiro, Sakamoto, Kazutoshi, Hashimoto, Michizane
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2010; Japan Antibiotics Research Assoc; Nature Publishing Group
• Subjects: 631/154/349; 631/326/2522; 631/326/41; Actinomycetales - metabolism; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Biotechnology & Applied Microbiology; Carbon - chemistry; Culture media; Culture Media - chemistry; Hydrogen-Ion Concentration; Hydroxylation; Immunology; Immunosuppressive Agents - metabolism; Life Sciences; Life Sciences & Biomedicine; Medicinal Chemistry; Microbiology; Nitrogen - chemistry; Nitrogen sources; Organic Chemistry; original-article; Peptides, Cyclic - metabolism; Pharmacology & Pharmacy; Science & Technology; Temperature; AS1387392; AS1429716; immunosuppressant; bioconversion; histone deacetylase inhibitor; MAMMALIAN HISTONE DEACETYLASE; HYDROXYLATION; MICROBIAL CONVERSION; Amycolatopsis azurea
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2010.108

We screened actinomycetes capable of converting AS1387392 to AS1429716 and identified those strains capable of hydroxylation. Amycolatopsis azurea JCM 3275 was found to be a particularly efficient strain, capable of converting AS1387392 to AS1429716, with a yield of 44% after 9 h. This strain can metabolize not only the hydroxylation of phenylalanine at the meta and para positions but also the reduction of hydroxyketones, as shown by the isolation of bioconversion products. Examination of more suitable conversion conditions showed that pH 7.8 and 25 °C were the optimum pH and temperature for bioconversion, respectively. We also demonstrated the effect of carbon and nitrogen sources in the culture media on hydroxylation. Using this strain, we were able to efficiently produce AS1429716 as a chemical template. Further derivatization studies may provide more effective, safer immunosuppressants than those that are currently on-market.