title: Acyl-CoA sensing by FasR to adjust fatty acid synthesis in Corynebacterium glutamicum.
abstract: Corynebacterium glutamicum, like Mycobacterium tuberculosis, is a member of the Corynebacteriales, which have linear fatty acids and as branched fatty acids the mycolic acids. We identified accD1 and fasA as key genes of fatty acid synthesis, encoding the β-subunit of the acetyl-CoA carboxylase and a type-I fatty acid synthase, respectively, and observed their repression during growth on minimal medium with acetate. We also identified the transcriptional regulator FasR and its binding sites in the 5′ upstream regions of accD1 and fasA. In the present work we establish by co-isolation and gel-mobility shifts oleoyl-CoA and palmitoyl-CoA as effectors of FasR, and show by DNA microarray analysis that in presence of exogeneous fatty acids accD1 and fasA are repressed. These results are evidence that acyl-CoA derivatives derived from extracellular fatty acids interact with FasR to repress the genes of fatty acid synthesis. This model also explains the observed repression of accD1 and fasA during growth on acetate, where apparently the known high intracellular acetyl-CoA concentration during growth on this substrate requires reduced accD1 and fasA expression for fine control of de novo fatty acid synthesis. Consequently, this mechanism ensures that membrane lipid homeostasis is maintained when specific nutrients are available resulting in increased acetyl-CoA concentration, as is the case with acetate, or when fatty acids are directly available from the extracellular environment. However, the genes specific to mycolic acid synthesis, which are in part shared with linear fatty acid synthesis, are not controlled by FasR, which is in agreement with the fact that they can not be supplied from the extracellular environment but that their synthesis fully depends on a constant supply of linear fatty acid chains.
authors.forename: Kristina
authors.initials: K
authors.lastname: Irzik
authors.forename: Jan
authors.initials: J
authors.lastname: van Ooyen
authors.forename: Jochem
authors.initials: J
authors.lastname: Gätgens
authors.forename: Karin
authors.initials: K
authors.lastname: Krumbach
authors.forename: Michael
authors.initials: M
authors.lastname: Bott
authors.forename: Lothar
authors.initials: L
authors.lastname: Eggeling
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000214:Acyl Coenzyme A / Q000378:metabolism*; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D048230:Corynebacterium glutamicum / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012329:RNA, Bacterial / Q000235:genetics
chemical_list: D000214:Acyl Coenzyme A; D026923:Amino Acid Transport Systems, Basic; D001426:Bacterial Proteins; D005227:Fatty Acids; C438905:LysG protein, Corynebacterium glutamicum; D012329:RNA, Bacterial; D000103:Acetyl-CoA Carboxylase