title: Genetic and transcriptional analysis of absA, an antibiotic gene cluster-linked two-component system that regulates multiple antibiotics in Streptomyces coelicolor.
abstract: In Streptomyces coelicolor, the AbsA1-AbsA2 two-component system regulates the expression of multiple antibiotic gene clusters. Here, we show that the response regulator encoded by the absA2 gene is a negative regulator of these antibiotic gene clusters. A genetic analysis shows that the phosphorylated form of the AbsA2 response regulator (phospho-AbsA2), generated by the cognate AbsA1 sensor histidine kinase, is required for normal growth phase regulation of antibiotic synthesis. In the absence of phospho-AbsA2, antibiotics are produced earlier and more abundantly. Overexpression of AbsA1 also deregulates antibiotic synthesis, apparently shifting the AbsA1 protein from a kinase-active to a phospho-AbsA2 phosphatase-active form. The absA1 and absA2 genes, which are adjacent, are located in one of the antibiotic gene clusters that they regulate, the cluster for the calcium-dependent antibiotic (CDA). The absA genes themselves are growth phase regulated, with phospho-AbsA2 responsible for growth phase-related positive autoregulation. We discuss the possible role and mechanism of AbsA-mediated regulation of antibiotic synthesis in the S. coelicolor life cycle.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824-1101, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Anderson
authors.forename: P
authors.initials: P
authors.lastname: Brian
authors.forename: W C
authors.initials: WC
authors.lastname: Champness
mesh_terms: D000880:Anthraquinones / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D007476:Ionophores / Q000378:metabolism; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D010455:Peptides; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D011353:Prodigiosin / Q000031:analogs & derivatives / Q000096:biosynthesis; D015398:Signal Transduction; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002118:Calcium; D007476:Ionophores; D010455:Peptides; D011353:Prodigiosin; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014157:Transcription Factors; C433524:AbsA2 protein, Streptomyces coelicolor; C040487:CDA antibiotic; C047347:undecylprodigiosin; C013390:actinorhodin; D000095622:Benzoisochromanequinones