title: The role of absC, a novel regulatory gene for secondary metabolism, in zinc-dependent antibiotic production in Streptomyces coelicolor A3(2).
abstract: The availability of zinc was shown to have a marked influence on the biosynthesis of actinorhodin in Streptomyces coelicolor A3(2). Production of actinorhodin and undecylprodigiosin was abolished when a novel pleiotropic regulatory gene, absC, was deleted, but only when zinc concentrations were low. AbsC was shown to control expression of the gene cluster encoding production of coelibactin, an uncharacterized non-ribosomally synthesized peptide with predicted siderophore-like activity, and the observed defect in antibiotic production was found to result from elevated expression of this gene cluster. Promoter regions in the coelibactin cluster contain predicted binding motifs for the zinc-responsive regulator Zur, and dual regulation of coelibactin expression by zur and absC was demonstrated using strains engineered to contain deletions in either or both of these genes. An AbsC binding site was identified in a divergent promoter region within the coelibactin biosynthetic gene cluster, adjacent to a putative Zur binding site. Repression of the coelibactin gene cluster by both AbsC and Zur appears to be required to maintain appropriate intracellular levels of zinc in S. coelicolor.
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK. andrew.hesketh@bbsrc.ac.uk
authors.forename: Andy
authors.initials: A
authors.lastname: Hesketh
authors.forename: Holger
authors.initials: H
authors.lastname: Kock
authors.forename: Saraspadee
authors.initials: S
authors.lastname: Mootien
authors.forename: Mervyn
authors.initials: M
authors.lastname: Bibb
mesh_terms: D000880:Anthraquinones / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D018983:DNA Footprinting; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D008954:Models, Biological; D008969:Molecular Sequence Data; D010080:Oxazoles / Q000378:metabolism*; D011353:Prodigiosin / Q000031:analogs & derivatives / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D048372:Streptomyces coelicolor / Q000502:physiology*; D013844:Thiazoles / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010080:Oxazoles; D011353:Prodigiosin; D012097:Repressor Proteins; D013844:Thiazoles; D015032:Zinc; C000600079:coelibactin; C047347:undecylprodigiosin; C013390:actinorhodin; D000095622:Benzoisochromanequinones