Affiliation:
1. Department of Biochemistry and Biomedical Sciences, McMaster University, Health Sciences Centre, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5
Abstract
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
, for which the phosphorylated form of AbsA2 (AbsA2∼P) is the agent of repression. In this study, we used chromatin immunoprecipitation to show that AbsA2 binds the promoter regions of
act
II-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
act
II-ORF4 and
redZ
in the hyperrepressive
absA1
mutant (C542) brought about pathway-specific restoration of actinorhodin and undecylprodigiosin production, respectively. Our results suggest that AbsA2∼P interacts with as many as four sites in the region that includes the
act
II-ORF4 promoter. These data suggest that AbsA2∼P inhibits antibiotic production by directly interfering with the expression of pathway-specific regulators of antibiotic biosynthetic gene clusters.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
86 articles.
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