MICROBIAL CONVERSION OF MILBEMYCINS: 30-OXIDATION OF MILBEMYCIN A₄ AND RELATED COMPOUNDS BY AMYCOLATA AUTOTROPHICA AND AMYCOLATOPSIS MEDITERRANEI

Abstract

Microorganisms were screened for their ability to modify milbemycin A₄ (la). Many strains, mostly actinomycetes and zygomycetes, were found to convert milbemycin A₄ (la) to one or more new products. Among these products, M-l, M-2, and M-3 were obtained using Amycolata autotrophica subsp. amethystina ATCC 35204, and were identified as 30-hydroxymilbemycin A₄ (1b), 26, 30-dihydroxymilbemycin A₄ (Ic), and milbemycin A₄ 30-oic acid (1d), respectively. Other milbemycins and LL-F28249α (7a) also underwent 30-hydroxylation by the microorganism. 22, 23-Dihydroavermectin B_1a (8a) was not hydroxylated at any position by A. autotrophica subsp. amethystina ATCC 35204, but a corresponding hydroxyl product at the C-30 position was obtained using Amycolatopsis mediterranei IFO 13415.