AbsA2P negatively regulates antibiotic production in Streptomyces coelicolor through interactions with the pathway-specific regulatory gene promoters

Department of Biochemistry & Biomedical Sciences, McMaster University, Health Sciences Centre, 1200 Main St W., Hamilton, Ontario, Canada L8N 3Z5

^* To whom correspondence should be addressed. Email: nodwellj{at}mcmaster.ca.

	Abstract

The AbsA two-component signal transduction system, comprised of the sensor kinase AbsA1 and the response regulator AbsA2, acts as a negative regulator of antibiotic production in Streptomyces coelicolor, where the phosphorylated form of AbsA2 is the agent of repression. In this study we have used chromatin immunoprecipitation to show that AbsA2 binds the promoter regions of actII-ORF4, cdaR and redZ, which encode pathway-specific activators for actinorhodin, calcium-dependent antibiotic and undecylprodigiosin, respectively. We confirm that these interactions also occur in vitro, and that the binding of AbsA2 to each gene is enhanced by phosphorylation. Induced expression of actII-ORF4 and redZ in the hyper-repressive absA1 mutant (C542) brought about pathway-specific restoration of actinorhodin and undecylprodigiosin production, respectively. Our results suggest that AbsA2P interacts with as many as four sites in the region that includes the actII-ORF4 promoter. These data suggest that AbsA2P inhibits antibiotic production by directly interfering with the expression of pathway-specific regulators of antibiotic biosynthetic gene clusters.