Reassessment of the Genetic Regulation of Fatty Acid Synthesis in Escherichia coli: Global Positive Control by the Functional Dual Regulator FadR
Reassessment of the Genetic Regulation of Fatty Acid Synthesis in Escherichia coli: Global Positive Control by the Functional Dual Regulator FadR
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DOI：
10.1128/jb.00064-15
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发表时间：
2015-06-01
影响因子：
3.2
通讯作者：
Bouveret, E.
中科院分区：
文献类型：
--
作者：
My, L.;Achkar, N. Ghandour;Bouveret, E.
在大肠杆菌中，FadR转录调节因子抑制脂肪酸降解（fad）基因的表达。然而，FadR也是fabA和fabB表达的激活剂，fabA和fabB是参与不饱和脂肪酸合成的两个基因。因此，FadR在维持膜中饱和和不饱和脂肪酸之间的平衡方面起着重要作用。我们最近发现FadR也激活fabH基因上游的启动子（L.我的，B。放大图片作者：Rekoske，J. J. Lemke，J. P. Viala，R. L. Gourse和E. Bouveret，J Bacteriol 195：3784-3795，2013，doi：10.1128/JB.00384-13）。此外，最近的转录组学和蛋白质组学数据表明，FadR激活大多数脂肪酸（FA）合成基因。在本研究中，我们测试了FadR在参与FA合成的所有基因的表达中的作用。我们发现FadR激活所有测试的FA合成基因的转录，并且我们确定了这些基因中每个基因的FadR结合位点。这就需要重新评估的accA和accB基因的转录起始位点之前描述的，我们提供的证据，驱动这些基因的表达的多个启动子的存在。我们进一步表明，FadR的调节影响细胞中FA合成酶的量。我们的研究结果表明，FadR是一个全面的调节FA代谢在E。在大肠杆菌中，它同时作为catalysts的阻遏物和analysts的激活物，这两种途径是直接相反的。奇怪的是，E.大肠杆菌，尽管如此，这是一个突出的模式细菌用于工程生物燃料生产使用FA合成途径。我们的工作确定了FadR功能性双重调节因子作为E.杆菌因为FadR也是FA降解的阻遏物，所以FadR既作为FA降解和合成的两个相反途径的阻遏物又作为激活物。我们的研究结果表明，在理解FA合成的遗传调控方面，即使在非常著名的细菌E。杆菌
In Escherichia coli, the FadR transcriptional regulator represses the expression of fatty acid degradation (fad) genes. However, FadR is also an activator of the expression of fabA and fabB, two genes involved in unsaturated fatty acid synthesis. Therefore, FadR plays an important role in maintaining the balance between saturated and unsaturated fatty acids in the membrane. We recently showed that FadR also activates the promoter upstream of the fabH gene (L. My, B. Rekoske, J. J. Lemke, J. P. Viala, R. L. Gourse, and E. Bouveret, J Bacteriol 195: 3784-3795, 2013, doi:10.1128/JB.00384-13). Furthermore, recent transcriptomic and proteomic data suggested that FadR activates the majority of fatty acid (FA) synthesis genes. In the present study, we tested the role of FadR in the expression of all genes involved in FA synthesis. We found that FadR activates the transcription of all tested FA synthesis genes, and we identified the FadR binding site for each of these genes. This necessitated the reassessment of the transcription start sites for accA and accB genes described previously, and we provide evidence for the presence of multiple promoters driving the expression of these genes. We showed further that regulation by FadR impacts the amount of FA synthesis enzymes in the cell. Our results show that FadR is a global regulator of FA metabolism in E. coli, acting both as a repressor of catabolism and an activator of anabolism, two directly opposing pathways.IMPORTANCEIn most bacteria, a transcriptional regulator tunes the level of FA synthesis enzymes. Oddly, such a global regulator still was missing for E. coli, which nonetheless is one of the prominent model bacteria used for engineering biofuel production using the FA synthesis pathway. Our work identifies the FadR functional dual regulator as a global activator of almost all FA synthesis genes in E. coli. Because FadR also is the repressor of FA degradation, FadR acts both as a repressor and an activator of the two opposite pathways of FA degradation and synthesis. Our results show that there are still discoveries waiting to be made in the understanding of the genetic regulation of FA synthesis, even in the very well-known bacterium E. coli.