Hormone-like factors influencing differentiation of Streptomyces cultures

Abstract: Actinomycetes produce and export small autoregulalory molecules, which act like prokaryotic hormones. They can promote or induce sporulation, aerial hyphae formation and antibiotic production. The mode of action of the λ-lactone AF is partly elucidated, those of the others are not known. These autoregulators (hormones) are effective if exogenously added to culture in proper time of the life cycle and in very low concentration. Since they influence the length of idiophase where secondary metabolites are produced their study may have pratical importance.     

Genes,enzymes and secondary metabolites in industrial microorganisms The 1995 Thom Award Lecture

Apparently contrasting aproaches, ie genetic engineering and screening of new microorganisms, play essential complementary roles to develop current industrial microbiology. Three topics, production and modification of milkclotting proteinases by genetic engineering, hormonal control of secondary metabolism in streptomyucetes, and screening of bioactive metabolites, are introduced as cases of such a hybrid approach, while symbiotic microorganisms are discussed as an example of the vastterra incognita still remaining for the future microbiology.     

The A-factor regulatory cascade and cAMP in the regulation of physiological and morphological development in Streptomyces griseus

In the A-factor regulatory cascade leading to the onset of streptomycin biosynthesis and aerial mycelium formation in Streptomyces griseus, the A-factor receptor protein (ArpA) serves as a DNA-binding repressor and A-factor releases the repression by binding to ArpA and dissociating it from the DNA. Mutants defective in arpA therefore produce streptomycin and aerial hyphae in the absence of A-factor. A gene that inhibits streptomycin production and aerial hyphae formation in an arpA mutant was cloned on a high-copy-number plasmid and found to encode a eukaryotic-type adenylate cyclase (CyaA). Consistent with this, an exogenous supply of cAMP at high concentration almost abolished streptomycin production and aerial hyphae formation. On the other hand, cAMP at lower concentrations stimulated or accelerated these developmental processes. The effects of cAMP were detectable only in arpA mutants, and not in the wild-type strain; an exogenous supply of cAMP or cyaA disruption in the wild-type strain caused almost no effect on these phenotypes. Thus the effects of cAMP became apparent only in the arpA-defective background. cAMP at high concentrations inhibited stringent response factor ppGpp production, which is important for the onset of antibiotic biosynthesis. cAMP also influenced the timing of tyrosine phosphorylation of more than nine proteins. These findings show that a cAMP regulatory relay for physiological and morphological development functions in a concerted and interdependent way with other signal transduction pathways. Journal of Industrial Microbiology & Biotechnology (2001) 27, 177–182. Received 21 September 1999/ Accepted in revised form 14 September 2000