title: Identification and characterization of Rv0494: a fatty acid-responsive protein of the GntR/FadR family from Mycobacterium tuberculosis.
abstract: Escherichia coli FadR, a member of the GntR family of transcription factors, plays dual roles in fatty acid metabolism. FadR-DNA binding is inhibited by fatty acyl-CoAs, and thus FadR acts as a sensor of the fatty acid level in bacteria. We have identified FadR-binding sites in the upstream regions of genes showing altered expression after the disruption of fatty acid biosynthesis in Mycobacterium tuberculosis. A FadR homologue in M. tuberculosis, Rv0494, was identified, which binds to its operator in the upstream region of the kas operon. We have shown that FadRMt (Rv0494) directly binds to long-chain fatty acyl-CoA and that binding quenches the intrinsic fluorescence of the purified protein. FadR-DNA binding can be impaired by long-chain fatty acyl-CoA compounds. Overexpression of Rv0494 in Mycobacterium bovis BCG reduced the basal level expression of kas operon genes, thereby suggesting the repressor nature of this protein in fatty acid synthase II regulation. This is the first report, to the best of our knowledge, of a GntR/FadR family protein acting as a fatty acid-responsive transcriptional regulator in M. tuberculosis, suggesting a possible role for this protein in mycolic acid biosynthesis.
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226021, India.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Biswas
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226021, India.
authors.forename: Debashis
authors.initials: D
authors.lastname: Dutta
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226021, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Department of Microbiology, University of Illinois, Urbana, Illinois, USA.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Zoology, Lucknow University, Lucknow, 226007, India.
authors.forename: Monisha
authors.initials: M
authors.lastname: Banerjee
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226021, India.
authors.forename: Bhupendra N
authors.initials: BN
authors.lastname: Singh
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D004269:DNA, Bacterial / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005810:Multigene Family; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009171:Mycolic Acids / Q000378:metabolism; D011485:Protein Binding; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D005227:Fatty Acids; D009171:Mycolic Acids; D014157:Transcription Factors