The FabR (YijC) Transcription Factor Regulates Unsaturated Fatty Acid Biosynthesis in Escherichia coli

Zhang, Yongmei; Marrakchi, Hédia; Rock, Charles O.

doi:10.1074/jbc.m201399200

Cited by 106 publications

(132 citation statements)

References 38 publications

(21 reference statements)

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“…A second protein called FabR was found to negatively regulate fabA and fabB (10,11). In the prior work the weak fabA promoter could not be mapped due to insensitivity of the methods then available, this raised the possibility that FabR might regulate function of this promoter.…”

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confidence: 99%

Escherichia coli Unsaturated Fatty Acid Synthesis

Feng

Cronan

2009

Journal of Biological Chemistry

163

108

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Although the unsaturated fatty acid (UFA) synthetic pathway of Escherichia coli is the prototype of such pathways, several unresolved issues have accumulated over the years. The key players are the fabA and fabB genes. Earlier studies of fabA transcription showed that the gene was transcribed from two promoters, with one being positively regulated by the FadR protein. The other weaker promoter (which could not be mapped with the technology then available) was considered constitutive because its function was independent of FadR. However, the FabR negative regulator was recently shown to represses fabA transcription. We report that the weak promoter overlaps the FadR-dependent promoter and is regulated by FabR. This promoter is strictly conserved in all E. coli and Salmonella enterica genomes sequenced to date and is thought to provide insurance against inappropriate regulation of fabA transcription by exogenous saturated fatty acids. Also, the fabAup promoter, a mutant promoter previously isolated by selection for increased FabA activity, was shown to be a promoter created de novo by a four-base deletion within the gene located immediately upstream of fabA. Demonstration of the key UFA synthetic reaction catalyzed by FabB has been elusive, although it was known to catalyze an elongation reaction. Strains lacking FabB are UFA auxotrophs indicating that the enzyme catalyzes an essential step in UFA synthesis. Using thioesterases specific for hydrolysis of short chain acyl-ACPs, the intermediates of the UFA synthetic pathway have been followed in vivo for the first time. These experiments showed that a fabB mutant strain accumulated less cis-5-dodecenoic acid than the parental wild-type strain. These data indicate that the key reaction in UFA synthesis catalyzed by FabB is elongation of the cis-3-decenoyl-ACP produced by FabA.The fabA gene of Escherichia coli encodes 3-hydroxydecanoyl-acyl carrier protein (ACP) 2 dehydratase/isomerase, a bifunctional enzyme that introduces the unsaturated fatty acid (UFA) double bond at the C10 level (1-3) (see Fig. 1). As expected fabA mutants require supplementation with UFA for growth (4). Although UFA synthesis can be considered a housekeeping function, fabA transcription is subject to an unexpectedly complex regulation. Work from this laboratory and others showed that fabA transcription is positively regulated by FadR, a protein that also functions as the repressor of the ␤-oxidation regulon (5-7). In that work the FadR-dependent promoter was identified as well as a second weaker promoter that was unaffected by FadR and thus was considered constitutively active (5, 6). The FadR-independent promoter is thought to ensure continued expression of fabA under conditions where FadR activation is compromised. E. coli fabA mutants lyse in the absence of UFA (3). Because FadR responds to CoA thioesters of both unsaturated and saturated fatty acids, E. coli could shut down UFA synthesis in response to saturated fatty acid (SFA) availability, a potential disaster. We have proposed that E. ...

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confidence: 99%

Escherichia coli Unsaturated Fatty Acid Synthesis

Feng

Cronan

2009

Journal of Biological Chemistry

163

108

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“…In bacteria, fatty acid incorporation and degradation are controlled at the transcriptional level. They have been mainly studied in Escherichia coli DiRusso & Nyström, 1998;Marrakchi et al, 2002;Rock & Cronan, 1996;Zhang et al, 2002) and Bacillus subtilis Schujman et al, 2003Schujman et al, , 2006. In E. coli, four regulatory systems, i.e.…”

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confidence: 99%

TetR-family transcriptional repressor Thermus thermophilus FadR controls fatty acid degradation

Agari

Sakamoto

et al. 2011

Microbiology

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In the extremely thermophilic bacterium Thermus thermophilus HB8, one of the four TetR-family transcriptional regulators, which we named T. thermophilus FadR, negatively regulated the expression of several genes, including those involved in fatty acid degradation, both in vivo and in vitro. T. thermophilus FadR repressed the expression of the target genes by binding pseudopalindromic sequences covering the predicted "10 hexamers of their promoters, and medium-to-long straight-chain (C10-18) fatty acyl-CoA molecules were effective for transcriptional derepression. An X-ray crystal structure analysis revealed that T. thermophilus FadR bound one lauroyl (C12)-CoA molecule per FadR monomer, with its acyl chain moiety in the centre of the FadR molecule, enclosed within a tunnel-like substrate-binding pocket surrounded by hydrophobic residues, and the CoA moiety interacting with basic residues on the protein surface. The growth of T. thermophilus HB8, with palmitic acid as the sole carbon source, increased the expression of FadR-regulated genes. These results indicate that in T. thermophilus HB8, medium-to-long straight-chain fatty acids can be used for metabolic energy under the control of FadR, although the major fatty acids found in this strain are iso-and anteiso-branchedchain (C15 and 17) fatty acids.

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“…FabR belongs to the TetR family of transcription regulators, and homologs of FabR are found exclusively in g-proteobacteria. Deletion of fabR in E. coli leads to significantly elevated levels of unsaturated fatty acids, specifically cis-vaccinate due to substantial increases in fabB transcription coupled with somewhat lower levels of fabA induction (17). FabR repressor binding site is downstream of the FadR activator binding site on both the fabA and fabB promoters.…”

Section: Control Of Unsaturated Fatty Acid Synthesis By Fabr In E Colimentioning

confidence: 99%

“…FabR is a second transcriptional regulator of type II FAS in E. coli (17). This factor is a transcriptional repressor of fabA and fabB, the two essential genes for unsaturated fatty acid formation (Table 1).…”

Section: Control Of Unsaturated Fatty Acid Synthesis By Fabr In E Colimentioning

confidence: 99%

Transcriptional regulation in bacterial membrane lipid synthesis

Zhang

Rock

2009

Journal of Lipid Research

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This review covers the main transcriptional mechanisms that control membrane phospholipid synthesis in bacteria. The fatty acid components are the most energetically expensive modules to produce; thus, the regulation of fatty acid production is very tightly controlled to match the growth rate of cells. Gram-negative and Gram-positive bacteria have evolved different structural classes of regulators to control the genes required for fatty acid biosynthesis. Also, there are other transcriptional regulators that allow the cells to alter the structure of fatty acids in existing phospholipid molecules or to modify the structures of exogenous fatty acids prior to their incorporation into the bilayer.

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The FabR (YijC) Transcription Factor Regulates Unsaturated Fatty Acid Biosynthesis in Escherichia coli

Cited by 106 publications

References 38 publications

Escherichia coli Unsaturated Fatty Acid Synthesis

Escherichia coli Unsaturated Fatty Acid Synthesis

TetR-family transcriptional repressor Thermus thermophilus FadR controls fatty acid degradation

Transcriptional regulation in bacterial membrane lipid synthesis

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