Reassessment of the Genetic Regulation of Fatty Acid Synthesis in Escherichia coli: Global Positive Control by the Dual Functional Regulator FadR

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 maintain...

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Bibliographic Details
Published in:	Journal of bacteriology Vol. 197; no. 11; pp. 1862 - 1872
Main Authors:	My, L, Ghandour Achkar, N, Viala, J. P, Bouveret, E
Format:	Journal Article
Language:	English
Published:	United States American Society for Microbiology 01-06-2015
Subjects:	bacteria Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Proteins - metabolism Bacteriology Base Sequence Binding Sites Biochemistry, Molecular Biology biofuels Biosynthesis E coli engineering Enzymes Escherichia coli Escherichia coli - chemistry Escherichia coli - genetics Escherichia coli - metabolism Fatty acids Fatty Acids - biosynthesis Gene expression Gene Expression Regulation, Bacterial genes Life Sciences metabolism Molecular Sequence Data Promoter Regions, Genetic Proteomics Repressor Proteins - chemistry Repressor Proteins - genetics Repressor Proteins - metabolism transcription factors Transcription, Genetic transcriptomics unsaturated fatty acids
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Summary:	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. IMPORTANCE In 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 .
Bibliography:	http://dx.doi.org/10.1128/JB.00064-15 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC4420907 Citation My L, Ghandour Achkar N, Viala JP, Bouveret E. 2015. Reassessment of the genetic regulation of fatty acid synthesis in Escherichia coli: global positive control by the dual functional regulator FadR. J Bacteriol 197:1862–1872. doi:10.1128/JB.00064-15.
ISSN:	0021-9193 1098-5530
DOI:	10.1128/jb.00064-15