Molecular mechanisms of the A-factor-dependent control of secondary metabolism in Streptomyces

Abstract

A-factor, 2-isocapryloyl-(3R)-hydroxymethyl-gamma-butyrolactone, is a microbial hormone controlling secondary metabolism and morphogenesis of Streptomyces griseus. The A-factor-receptor protein present in the cytoplasm is a repressor-type regulator; it plays a role in repressing streptomycin production and sporulation while the binding of A-factor to the receptor protein releases its repression. Thus, secondary metabolism and sporulation of S. griseus involve a step of hormonal regulation by A-factor. The afsR gene codes for a global regulatory protein of 993 amino acids controlling positively secondary metabolic formation in Streptomyces coelicolor A3(2), probably at the transcriptional level. This protein comprises two domains, i.e., an ATP-binding domain at its NH2-terminal portion and a DNA-binding domain with a helix-turn-helix motif at its COOH-terminal portion. The AfsR protein is found to be phosphorylated. It is assumed that the extent of phosphorylation-dephosphorylation of the AfsR protein modulates the expression of genes responsible for secondary metabolic formation.