Induction of streptomycin-inactivating enzyme by A-factor in Streptomyces griseus

The effect of A-factor on streptomycin resistance and productivity in Streptomyces griseus and S. bikiniensis was studied using A-factor-negative mutants. Resistance of several of these mutants was markedly increased by adding A-factor to the growing medium, as also was their streptomycin productivity. The A-factor induced resistance was due to inactivation by streptomycin-6-phosphotransferase, and enzyme synthesis in these mutants was completely dependent on the presence of A-factor. In the case of S. griseus 2247 where streptomycin productivity was independent of A-factor, resistance and synthesis of the inactivating enzyme were also independent of A-factor. A-Factor-negative mutants of S. griseus showed a decreased level of NADP-glycohydrolase and an increased level of several NADP-linked dehydrogenases, but these enzymes did not return to parental levels in cultures supplemented with A-factor. A-Factor seems to regulate streptomycin biosynthesis, not through an indirect metabolic sequence involving these enzymes but, more likely, by directly stimulating synthesis of enzyme(s) in the biosynthetic pathway.