Transcription of the Escherichia coli Fatty Acid Synthesis OperonfabHDGIs Directly Activated by FadR and Inhibited by ppGpp

Abstract

bIn Escherichia coli, FadR and FabR are transcriptional regulators that control the expression of fatty acid degradation and unsaturated fatty acid synthesis genes, depending on the availability of fatty acids. In this report, we focus on the dual transcriptional regulator FadR. In the absence of fatty acids, FadR represses the transcription of fad genes required for fatty acid degradation. However, FadR is also an activator, stimulating transcription of the products of the fabA and fabB genes responsible for unsaturated fatty acid synthesis. In this study, we show that FadR directly activates another fatty acid synthesis promoter, PfabH, which transcribes the fabHDG operon, indicating that FadR is a global regulator of both fatty acid degradation and fatty acid synthesis. We also demonstrate that ppGpp and its cofactor DksA, known primarily for their role in regulation of the synthesis of the translational machinery, directly inhibit transcription from the fabH promoter. ppGpp also inhibits the fadR promoter, thereby reducing transcription activation of fabH by FadR indirectly. Our study shows that both ppGpp and FadR have direct roles in the control of fatty acid promoters, linking expression in response to both translation activity and fatty acid availability.

The Fatty Acid Regulator FadR Influences the Expression of the Virulence Cascade in the El Tor Biotype of Vibrio cholerae by Modulating the Levels of ToxT via Two Different Mechanisms

“…We previously demonstrated that FadR also regulates both of these processes in V. cholerae (33) and have now extended these studies to show that sequences with similarity to the E. coli FadR binding site consensus are necessary for the FadR-dependent expression of these genes in V. cholerae. FadR has recently been shown to activate the expression of two operons involved in SFA biosynthesis in E. coli (29). We have similarly found that FadR also plays a role in activating the expression of these operons in V. cholerae.…”

“…It has been shown that in addition to its roles in FA degradation and UFA biosynthesis, FadR activates the expression of genes involved in SFA biosynthesis in E. coli (29,30). Unlike in mammals, where FAs are synthesized by a large multifunctional protein known as type I synthase (22,43), bacteria produce a type II synthase composed of individual enzymes that catalyze discrete steps in the process, with each intermediate attached to the universal and highly conserved acyl carrier protein (ACP) (22,43).…”

“…Unlike in mammals, where FAs are synthesized by a large multifunctional protein known as type I synthase (22,43), bacteria produce a type II synthase composed of individual enzymes that catalyze discrete steps in the process, with each intermediate attached to the universal and highly conserved acyl carrier protein (ACP) (22,43). Specifically, it has been shown that FadR activates the expression of the fabH promoter, which drives the expression of the fabHDG operon, encoding three enzymes involved in SFA biosynthesis, and shows a modest activation of the acpP promoter, which controls the expression of the gene encoding ACP, acpP, coexpressed with another SFA biosynthetic enzyme encoded by fabF (29). Since the arrangement of the SFA genes in V. cholerae is similar to that in E. coli (Fig.…”

(p)ppGpp modulates cell size and the initiation of DNA replication in Caulobacter crescentus in response to a block in lipid biosynthesis

“…In addition to modulating cell size, (p)ppGpp was found to inhibit the transcription of fabH and other lipid biosynthetic genes in E. coli (My et al, 2013;Podkovyrov & Larson, 1996). The transcription of a group of lipid biosynthetic genes (including plsX, which is in the same operon as fabH) was also inhibited in carbon-starved C. crescentus (Boutte & Crosson, 2011), suggesting a conserved regulatory pathway.…”

Prospects of a new antistaphylococcal drug batumin revealed by molecular docking and analysis of the complete genome sequence of the batumin-producer Pseudomonas batumici UCM B-321

“…[18], who reported that the fatty acid biosynthesis and particularly fabHDG operon in E. coli was inhibited by (p)ppGpp through FadR and FabR transcriptional regulators. This physiologically process is not critical for many bacteria, as they can compensate the lack of synthesized fatty acids by uptake of exogenous molecules.…”