Department of Microbiology, University of Illinois, Urbana, Illinois, United States of America.
PLoS One. 2012;7(9):e46275. doi: 10.1371/journal.pone.0046275. Epub 2012 Sep 28.
Escherichia coli FadR plays two regulatory roles in fatty acid metabolism. FadR represses the fatty acid degradation (fad) system and activates the unsaturated fatty acid synthetic pathway. Cross-talk between E. coli FadR and the ArcA-ArcB oxygen-responsive two-component system was observed that resulted in diverse regulation of certain fad regulon β-oxidation genes. We have extended such analyses to the fadL and fadD genes, the protein products of which are required for long chain fatty acid transport and have also studied the role of a third global regulator, the CRP-cAMP complex. The promoters of both the fadL and fadD genes contain two experimentally validated FadR-binding sites plus binding sites for ArcA and CRP-cAMP. Despite the presence of dual binding sites FadR only modestly regulates expression of these genes, indicating that the number of binding sites does not determine regulatory strength. We report complementary in vitro and in vivo studies indicating that the CRP-cAMP complex directly activates expression of fadL and fadD as well as the β-oxidation gene, fadH. The physiological relevance of the fadL and fadD transcription data was validated by direct assays of long chain fatty acid transport.
大肠杆菌 FadR 在脂肪酸代谢中发挥两种调节作用。FadR 抑制脂肪酸降解（fad）系统并激活不饱和脂肪酸合成途径。观察到大肠杆菌 FadR 与 ArcA-ArcB 氧响应双组分系统之间的串扰，导致某些 fad 调控子β-氧化基因的多样化调节。我们将这些分析扩展到 fadL 和 fadD 基因，这两个基因的蛋白质产物是长链脂肪酸转运所必需的，并且还研究了第三个全局调节剂 CRP-cAMP 复合物的作用。 fadL 和 fadD 基因的启动子都包含两个经过实验验证的 FadR 结合位点，外加 ArcA 和 CRP-cAMP 的结合位点。尽管存在双重结合位点，但 FadR 仅适度调节这些基因的表达，表明结合位点的数量并不决定调节强度。我们报告了互补的体外和体内研究，表明 CRP-cAMP 复合物直接激活 fadL 和 fadD 以及β-氧化基因 fadH 的表达。通过直接测定长链脂肪酸转运，验证了 fadL 和 fadD 转录数据的生理相关性。
