Bioconversion of milbemycin-related compounds: Isolation and utilization of non-producer, strain RNBC-5-51

Article abstract of DOI:10.7164/antibiotics.52.620

A non-producing strain, the so-called strain RNBC-5-51 SANK 60198, was isolated during a screening program of strain improvement in the milbemycin production. Strain RNBC-5-51 indicated almost the same characteristics as those in the parent strain, that is, the abundant spore formation on agar media and the good growth in liquid media. But it does not produce any kind of milbemycins. In addition, strain RNBC-5-51 accumulated precursor-like compounds of milbemycin-polyketide, the production of which were inhibited by the addition of cerulenin. In the bioconversion experiments, strain RNBC-5-51 converted milbemycin β₆ and A₄ to milbemycin α₁₄, and milbemycin β₇ and A₃ to milbemycin α₁₁, respectively. This strain also converted milbemycin D and avermectin B(1a), to 26-(3-methyl-2-butenoyloxy)milbemycin D and 26-(3-methyl-2-butenoyloxy)avermectin B(1a), respectively. These results suggest that milbemycin α₁₁ is biosynthesized through the same route as milbemycin α₁₄, and the mutated step in strain RNBC-5-51 might be in the polyketide synthetic pathway of milbemycins. Strain RNBC-5-51 loses the ability for de novo synthesis of milbemycins, but it retains the ability to bioconvert the milbemycin skeleton. This strain might be useful for C-26 modification of milbemycin-related compounds.