title: Characterization of SAV7471, a TetR-family transcriptional regulator involved in the regulation of coenzyme A metabolism in Streptomyces avermitilis.
abstract: The role of a tetR transcriptional regulatory gene (SAV7471) in avermectin production in the Gram-positive soil bacterium Streptomyces avermitilis was investigated by gene deletion, complementation, and overexpression experiments. Gene deletion of the SAV7471 open reading frame resulted in avermectin overproduction. The deletion also resulted in overexpression of SAV7472-SAV7473 transcripts, which encode a protein of unknown function and a flavoprotein possibly involved in pantothenate and coenzyme A (CoA) metabolism. EMSAs and footprinting assays showed that SAV7471 can bind to two palindromic sequences with high similarity in the intergenic region between SAV7471 and SAV7472, a region that contains the apparent transcription start sites for each gene detected by rapid amplification of 5' cDNA ends (5'-RACE). In addition to SAV7472-SAV7473, at least two genes (SAV1104 and SAV1258) involved in CoA metabolism are negatively controlled by SAV7471. By negatively regulating the transcription of the target genes SAV7472-SAV7473 and other genes involved in CoA metabolism, SAV7471 may affect cellular metabolic flux and may thereby indirectly regulate avermectin biosynthesis.
authors.affiliation: State Key Laboratories for Agro-biotechnology and Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Yan
authors.forename: Libin
authors.initials: L
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Song
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Jilun
authors.initials: J
authors.lastname: Li
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003065:Coenzyme A / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D007559:Ivermectin / Q000031:analogs & derivatives / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015534:Trans-Activators; D007559:Ivermectin; C019264:avermectin; D003065:Coenzyme A
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