Avermectin B2 O-methyltransferase activity in "Streptomyces avermitilis" mutants that produce increased amounts of the avermectins

The level of activity of avermectin B O-methyltransferase, the enzyme which catalyzes the conversion of avermectin B components to avermectin A components, was analyzed in a series of "Streptomyces avermitilis" mutants selected for increased production of the avermectins. In all of the mutants, increased avermectin production was accompanied by increased avermectin B O-methyltransferase activity. Both the average specific activity and the maximum observed specific activity of avermectin B O-methyltransferase increased in direct proportion to avermectin production. The level of avermectin B O-methyltransferase alone did not determine the extent of conversion of avermectin B components to avermectin A components, since a constant ratio of B components to A components was maintained throughout the fermentation even though avermectin B O-methyltransferase specific activity varied three- to fivefold. These results indicate that avermectin B O-methyltransferase is not rate limiting. The correlation between avermectin B O-methyltransferase specific activity and avermectin production is compatible with the hypothesis that genes coding for successive steps in the same secondary metabolite biosynthetic pathway are coordinately regulated.