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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.
Hara et al. (Fri,) studied this question.