title: The regulatory role of Streptomyces coelicolor TamR in central metabolism.
abstract: Trans-aconitate methyltransferase regulator (TamR) is a member of the ligand-responsive multiple antibiotic resistance regulator (MarR) family of transcription factors. In Streptomyces coelicolor, TamR regulates transcription of tamR (encoding TamR), tam (encoding trans-aconitate methyltransferase) and sacA (encoding aconitase); up-regulation of these genes promotes metabolic flux through the citric acid cycle. DNA binding by TamR is attenuated and transcriptional derepression is achieved on binding of ligands such as citrate and trans-aconitate to TamR. In the present study, we show that three additional genes are regulated by S. coelicolor TamR. Genes encoding malate synthase (aceB1; SCO6243), malate dehydrogenase (mdh; SCO4827) and isocitrate dehydrogenase (idh; SCO7000) are up-regulated in vivo when citrate and trans-aconitate accumulate, and TamR binds the corresponding gene promoters in vitro, a DNA binding that is attenuated by cognate ligands. Mutations to the TamR binding site attenuate DNA binding in vitro and result in constitutive promoter activity in vivo. The predicted TamR binding sites are highly conserved in the promoters of these genes in Streptomyces species that encode divergent tam-tamR gene pairs, suggesting evolutionary conservation. Like aconitase and trans-aconitate methyltransferase, malate dehydrogenase, isocitrate dehydrogenase and malate synthase are closely related to the citric acid cycle, either catalysing individual reaction steps or, in the case of malate synthase, participating in the glyoxylate cycle to produce malate that enters the citric acid cycle to replenish the intermediate pool. Taken together, our data suggest that TamR plays an important and conserved role in promoting metabolic flux through the citric acid cycle.
authors.affiliation: *Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, U.S.A.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.affiliation: *Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, U.S.A.
authors.forename: Smitha
authors.initials: S
authors.lastname: Sivapragasam
authors.affiliation: *Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, U.S.A.
authors.forename: Anne
authors.initials: A
authors.lastname: Grove
mesh_terms: D000156:Aconitic Acid / Q000378:metabolism; D001426:Bacterial Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle; D004790:Enzyme Induction; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D007521:Isocitrate Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008291:Malate Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008292:Malate Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000819:agonists / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D013045:Species Specificity; D048372:Streptomyces coelicolor / Q000201:enzymology / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D050505:Mutant Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D019343:Citric Acid; D000156:Aconitic Acid; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D008780:Methyltransferases; C119073:aconitate methyltransferase; D008292:Malate Synthase