A-factor and streptomycin biosynthesis in Streptomyces griseus.

Accumulating data have shown that the metabolites with a gamma-butyrolactone ring functions as an autoregulatory factor or a microbial hormone for the expression of various phenotypes not only in a variety of Streptomyces spp. but also in the distantly related bacteria. A-factor, as a representative of this type of autoregulators, triggers streptomycin biosynthesis and cellular differentiation in Streptomyces griseus. A model for the A-factor regulatory cascade on the basis of recent work is as follows. At an early step in the A-factor regulatory relay, the positive A-factor signal is first received by an A-factor receptor protein that is comparable in every aspect to eukaryotic hormone receptors, and then, via one or more regulatory steps, transmitted to an A-factor-responsive protein that binds to the upstream activation sequence of the strR gene, a regulatory gene in the streptomycin biosynthetic gene cluster. The StrR protein thus induced appears to activate the other streptomycin biosynthetic genes. This review summarizes the characteristics of A-factor as a microbial hormone and the A-factor regulatory relay leading to streptomycin production.