A microbial hormone, A-factor, as a master switch for morphological differentiation and secondary metabolism in...

The Gram-positive, soil-inhabiting, filamentous bacterial genus Streptomyces employs gamma-butyrolactones as chemical signalling molecules or microbial hormones, together with their specific receptors, to regulate morphological and/or physiological differentiation. The A-factor regulatory cascade in streptomycin-producing Streptomyces griseus commences aerial mycelium formation and production of all the secondary metabolites including streptomycin. The molecular mechanism by which A-factor triggers streptomycin biosynthesis or the A-factor signal is transmitted to the streptomycin biosynthetic gene cluster has been elucidated. A transcriptional activator AdpA at one of the regulatory steps switches on many genes required for both morphological development and secondary metabolism. Most of the gene cluster for secondary metabolite biosynthesis appear to receive the A-factor signal at the respective pathway-specific transcriptional activator genes via AdpA. Accumulating evidence has shown that a pair of genes encoding a probable gamma-butyrolactone biosynthetic enzyme (AfsA-like protein) and its specific receptor (ArpA-like protein) is contained in a number of biosynthetic gene clusters for secondary metabolites in various Streptomyces species and controls the biosynthesis of the respective metabolites by activating the pathway-specific regulatory genes. Some strains contain multiple pairs of afsA-arpA. It is conceivable that, because of the almost same sites bound by various receptor proteins, the multiple ArpA-like proteins with the same or different ligand specificity in a cell competitively bind the same target sites, thus allowing the cell to grow healthy and to produce antibiotics in response to environmental conditions.