FapR, a bacterial transcription factor involved in global regulation of membrane lipid biosynthesis.
Bacterial cells exert exquisite control over the biosynthesis of their membrane lipids, but the mechanisms are obscure. We describe the identification and purification from Bacillus subtilis of a transcription factor, FapR, that controls the expression of many genes involved in fatty acid and phospholipid metabolism (the fap regulon). Expression of this fap regulon is influenced by antibiotics that specifically inhibit the fatty acid biosynthetic pathway. We show that FapR negatively regulates fap expression and that the effects of antibiotics on fap expression are mediated by FapR. We further show that decreasing the cellular levels of malonyl-CoA, an essential molecule for fatty acid elongation, inhibits expression of the fap regulon and that this effect is FapR dependent. Our results indicate that control of FapR by the cellular pools of malonyl-CoA provides a mechanism for sensing the status of fatty acid biosynthesis and to adjust the expression of the fap regulon accordingly.
Instituto de Biología Molecular y Celular de Rosario (IBR), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000-, Rosario, Argentina.
Gustavo E
GE
Schujman
Luciana
L
Paoletti
Alan D
AD
Grossman
Diego
D
de Mendoza
D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002455:Cell Division; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008563:Membrane Lipids / Q000096:biosynthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C067955:FAPR protein, E coli; D005227:Fatty Acids; D008563:Membrane Lipids; D014157:Transcription Factors; D008316:Malonyl Coenzyme A