title: LAL regulators SCO0877 and SCO7173 as pleiotropic modulators of phosphate starvation response and actinorhodin biosynthesis in Streptomyces coelicolor.
abstract: LAL regulators (Large ATP-binding regulators of the LuxR family) constitute a poorly studied family of transcriptional regulators. Several regulators of this class have been identified in antibiotic and other secondary metabolite gene clusters from actinomycetes, thus they have been considered pathway-specific regulators. In this study we have obtained two disruption mutants of LAL genes from S. coelicolor (Δ0877 and Δ7173). Both mutants were deficient in the production of the polyketide antibiotic actinorhodin, and antibiotic production was restored upon gene complementation of the mutants. The use of whole-genome DNA microarrays and quantitative PCRs enabled the analysis of the transcriptome of both mutants in comparison with the wild type. Our results indicate that the LAL regulators under study act globally affecting various cellular processes, and amongst them the phosphate starvation response and the biosynthesis of the blue-pigmented antibiotic actinorhodin. Both regulators act as negative modulators of the expression of the two-component phoRP system and as positive regulators of actinorhodin biosynthesis. To our knowledge this is the first characterization of LAL regulators with wide implications in Streptomyces metabolism.
authors.affiliation: Institute of Biotechnology INBIOTEC, León, Spain.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Guerra
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-García
authors.forename: Javier
authors.initials: J
authors.lastname: Santos-Aberturas
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Vicente
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Payero
authors.forename: Juan F
authors.initials: JF
authors.lastname: Martín
authors.forename: Jesús F
authors.initials: JF
authors.lastname: Aparicio
mesh_terms: D000880:Anthraquinones / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial / Q000235:genetics; D005816:Genetic Complementation Test; D058685:Genetic Pleiotropy / Q000187:drug effects; D007700:Kinetics; D020411:Oligonucleotide Array Sequence Analysis; D010710:Phosphates / Q000172:deficiency* / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics; D048372:Streptomyces coelicolor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D001426:Bacterial Proteins; D010710:Phosphates; D012097:Repressor Proteins; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins; C013390:actinorhodin; D000095622:Benzoisochromanequinones