1999 Volume 52 Issue 7 Pages 620-627
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 Bla, to 26-(3-methyl-2-butenoyloxy)milbemycin D and 26-(3-methyl-2-butenoyloxy)avermectin Bla, 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.
