Transcriptional regulation of Streptomyces coelicolor pathway-specific antibiotic regulators by the absA and absB loci.

The four antibiotics produced by Streptomyces coelicolor are all affected by mutations in the absA and absB loci. The absA locus encodes a putative two-component signal transduction system, and the absB locus encodes a homolog of Escherichia coli RNase III. We assessed whether these loci control synthesis of the antibiotics actinorhodin and undecylprodigiosin by regulating transcript abundance from the biosynthetic and regulatory genes specific for each antibiotic. Strains that were Abs- (for antibiotic synthesis deficient) due to mutations in absA or absB were examined. In the Abs- absA mutant strain, transcripts for the actinorhodin biosynthetic genes actVI-ORF1 and actI, and for the pathway-specific regulatory gene actII-ORF4, were substantially lower in abundance than in the parent strain. The level of the transcript for the undecylprodigiosin pathway-specific regulatory gene redD was similarly reduced in this mutant. Additionally, a strain that exhibits precocious hyperproduction of antibiotics (Pha phenotype) due to disruption of the absA locus contained elevated levels of the actVI-ORF1, actII-ORF4, and redD transcripts. In the absB mutant strain, actVI-ORF1, actI, actII-ORF4, and redD transcript levels were also substantially lower than in the parent strain. These results establish that the abs genes affect production of antibiotics through regulation of expression of the antibiotic-specific regulatory genes in S. coelicolor.