Regulation of secondary metabolism and cell differentiation by A-factor and protein phosphorylation in Streptomyces.

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(1) The A-factor recepor protein (ArpA) was purified from S.griseus and arpA was cloned by PCR.We also cloned two arpA homologs from S.coelicolor A3 (2), which probably controlled antibiotic production in this strain, as determined by the phenotypes of each of disruptants.(2) Transcription of amfR,a regulatory gene for aerial mycelium formation in S.griseus, was controlled by A-factor. A protein able to bind to its promoter region was purified and its gene was cloned.(3) An afsK homolog (afsK2) was cloned from S.griseus. Genetic studies showed that the afsK2 gene is involved in aerial mycelium formation under the conditons of high osmolality(4) Upstream from afsA was present a gene encoding a protein similar to prokaryotic transcriptional factors. The expression of afsA therefore apeared to be controlled by this upstream gene.(5) An A-factor-responsive transcriptional activator (Adp) that bindsto the strR promoter was purified to homogeneity. The molecular mass of Adp was 40 kDa.(6) A tyrosine phosphatase gene was cloned from S.coelicolor A3 (2) as a gene that caused pigmentation in S.lividans. The phosphatase produced in E.coli showed a tyrosine phosphatase activity.