Regulation by A-factor and afsR of Secondary Metabolism and Morphogenesis in Streptomyces.

Abstract
A-factor (2-isocapryloyl-3R-hydroxymethyl-γ-butyrolactone) is a microbial hormone that functions as a key switch for secondary metabolite formation and cell differentiation in Streptomyces griseus. Genetic and biochemical studies on the A-factor-binding protein have implied that the binding protein plays a role in repressing streptomycin (Sm) production and sporulation while the binding of A-factor to the binding protein releases its repression. The positive A-factor signal is transferred, probably via some additional unknown regulatory proteins, to the strR gene, a putative regulator for Sm biosynthesis. The StrR product, in turn, activates the other Sm production genes. A global regulatory gene, afsR, of Streptomyces coelicolor A3(2) encodes a 993-amino acid protein that is phosphorylated by a specific phosphokinase present in the same organism. Characterization of AfsR by means of site-directed mutagenesis has revealed that phosphorylated AfsR stimulates globally transcription of antibiotic production genes. It is most likely that the AfsR protein and the AfsR-phosphokinase compose a two-component regulatory system.

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