“Eucaryotic” Signal Transduction Systems in the Bacterial Genus Streptomyces

Abstract

A microbial hormone, A-factor, controls streptomycin production, streptomycin resistance, and aerial mycelium formation in Streptomyces griseus. A-factor exerts its regulatory role by binding to a specific receptor protein which, in the absence of A-factor, acts as a repressor-type regulator for these morphological and physiological differentiation. In the signal relay leading to streptomycin production, the A-factor signal is transmitted from the A-factor receptor to the upstream activation sequence of a regulatory gene, strR, in the streptomycin biosynthetic gene cluster via an A-factor-dependent protein that acts as a transcription factor for strR. The signal relay leading to aerial mycelium formation includes proteins similar to response regulators of the procaryotic two-component regulatory systems and to a family of membrane translocators engaged in ATP-dependent secretion mechanisms. Accumulating data show that a large family of γ-butyrolactones act as autoregulators in a wide variety of Streptomyces spp. In addition to the hormonal control by the autoregulators, secondary metabolism and morphogenesis are controlled by signal transduction systems via both procaryotic and eucaryotic protein kinases. A pair of the AfsQ1 and AfsQ2 proteins constituting a procaryotic-type histidine-aspartate phosphotransfer system globally controls secondary metabolite formation in Streptomyces coelicolor A3(2). Another pair of proteins, AfsK and AfsR, which also serves as a global regulator for secondary metabolism in S. coelicolor, constitutes an eucaryotic-type phosphotransfer system in which a protein serine/threonine/tyrosine kinase AfsK phosphorylates serine and threonine residues of AfsR. A wide distribution of DNA sequences homologous with the afsQ1/afsQ2 and afsK/afsR genes suggests that both procaryotic and eucaryotic protein kinases control secondary metabolism in general in Streptomyces. Inhibition by K-252a and staurosporine, known as eucaryotic protein kinase inhibitors, of antibiotic production and aerial mycelium formation of S. griseus and S. coelicolor supports this idea.