fadR

FadR is a transcriptional regulator of fatty acid metabolism found in bacteria, notably Escherichia coli. It regulates a fatty acid metabolism regulon that controls genes involved in fatty acid degradation (beta-oxidation) and fatty acid biosynthesis.

In the absence of fatty acids, FadR binds to specific DNA sites in the promoters of fad genes such as fadD, fadE, and fadBA, repressing their transcription, and at the same time activating transcription of fab genes (e.g., fabA, fabB) involved in unsaturated fatty acid synthesis. When long-chain acyl-CoA molecules accumulate, they bind FadR, causing a conformational change that reduces its affinity for DNA. This results in derepression of beta-oxidation genes and repression of fatty acid biosynthesis genes, thereby shifting metabolism toward fatty acid degradation.

The FadR regulon thus acts as a global regulator that coordinates fatty acid uptake and utilization with membrane lipid synthesis. FadR is typically described as a DNA-binding transcription factor with a modular architecture consisting of an N-terminal DNA-binding domain and a C-terminal effector-binding domain that recognizes long-chain acyl-CoA.

In Escherichia coli and related bacteria, FadR is encoded by the fadR gene. The regulatory system provides a mechanism for the cell to adapt transcriptional programs to the availability of fatty acids, balancing catabolic and anabolic pathways to match metabolic needs.