Enhancing fatty acid production by the expression of the regulatory transcription factor FadR

Fatty acids are important precursors to biofuels. The Escherichia coli FadR is a transcription factor that regulates several processes in fatty acid biosynthesis, degradation, and membrane transport. By tuning the expression of FadR in an engineered E. coli host, we were able to increase fatty acid titer by 7.5-fold over our previously engineered fatty acid-producing strain, reaching 5.2±0.5g/L and 73% of the theoretical yield. The mechanism by which FadR enhanced fatty acid yield was studied by whole-genome transcriptional analysis (microarray) and targeted proteomics. Overexpression of FadR led to transcriptional changes for many genes, including genes involved in fatty acid pathways. The biggest transcriptional changes in fatty acid pathway genes included fabB, fabF, and accA. Overexpression of any of these genes alone did not result in a high yield comparable to fadR expression, indicating that FadR enhanced fatty acid production globally by tuning the expression levels of many genes to optimal levels. ► FadR overexpression increased fatty acid yield by 7.5-fold under optimal condition. ► We produced 5.2g/L fatty acids, reaching 73% of theoretical yield. ► FadR expression leads to many transcriptional changes. ► Expression of single gene examined did not result in a high fatty acid yield. ► FadR enhanced fatty acid production by tuning the expression levels of many genes.