title: FasR, a novel class of transcriptional regulator, governs the activation of fatty acid biosynthesis genes in Streptomyces coelicolor.
abstract: Membrane lipid homeostasis is essential for bacterial survival and adaptation to different environments. The regulation of fatty acid biosynthesis is therefore crucial for maintaining the correct composition and biophysical properties of cell membranes. This regulation implicates a biochemical control of key enzymes and a transcriptional regulation of genes involved in lipid metabolism. In Streptomyces coelicolor we found that control of lipid homeostasis is accomplished, at least in part, through the transcriptional regulation of fatty acid biosynthetic genes. A novel transcription factor, FasR (SCO2386), controls expression of fabDHPF operon and lies immediately upstream of fabD, in a cluster of genes that is highly conserved within actinomycetes. Disruption of fasR resulted in a mutant strain, with severe growth defects and a delay in the timing of morphological and physiological differentiation. Expression of fab genes was downregulated in the fasR mutant, indicating a role for this transcription factor as an activator. Consequently, the mutant showed a significant drop in fatty acid synthase activity and triacylglyceride accumulation. FasR binds specifically to a DNA sequence containing fabDHPF promoter region, both in vivo and in vitro. These data provide the first example of positive regulation of genes encoding core proteins of saturated fatty acid synthase complex.
authors.affiliation: Microbiology Division, Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531 (S2002LRK) Rosario, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Arabolaza
authors.forename: Matilde
authors.initials: M
authors.lastname: D'Angelo
authors.forename: Santiago
authors.initials: S
authors.lastname: Comba
authors.forename: Hugo
authors.initials: H
authors.lastname: Gramajo
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D006706:Homeostasis; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D009876:Operon; D011401:Promoter Regions, Genetic; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; D014157:Transcription Factors