Schujman Gustavo E, Paoletti Luciana, Grossman Alan D, de Mendoza Diego
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.
Dev Cell. 2003 May;4(5):663-72. doi: 10.1016/s1534-5807(03)00123-0.
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.
细菌细胞对其膜脂生物合成进行精确控制，但其机制尚不清楚。我们描述了从枯草芽孢杆菌中鉴定和纯化一种转录因子FapR的过程，该转录因子控制许多参与脂肪酸和磷脂代谢的基因（fap操纵子）的表达。这种fap操纵子的表达受到特异性抑制脂肪酸生物合成途径的抗生素的影响。我们表明，FapR负向调节fap表达，并且抗生素对fap表达的影响是由FapR介导的。我们进一步表明，降低丙二酰辅酶A（脂肪酸延长所需的必需分子）的细胞水平会抑制fap操纵子的表达，并且这种效应是FapR依赖性的。我们的结果表明，丙二酰辅酶A的细胞池对FapR的控制提供了一种感知脂肪酸生物合成状态并相应调整fap操纵子表达的机制。
