FadR, transcriptional co-ordination of metabolic expediency

Abstract

FadR is an Escherichia coli transcriptional regulator that optimizes fatty acid metabolism in response to exogenously added fatty acids. Many bacteria grow well on long-chain fatty acids as sole carbon source, but at the expense of consuming a useful structural material. Exogenous fatty acids are readily incorporated into membrane phospholipids in place of the acyl chains synthesized by the organism, and phospholipids composed of any of a large variety of exogenously derived acyl chains make biologically functional membranes. It would be wasteful for bacteria to degrade fatty acids to acetyl-CoA and then use this acetyl-CoA to synthesize the same (or functionally equivalent) fatty acids for phospholipid synthesis. This line of reasoning suggests that bacteria might shut down endogenous fatty acid synthesis on the addition of long-chain fatty acids to the growth medium. Moreover, this shutdown could be closely coupled to fatty acid degradation, such that a bacterial cell would use a portion of the exogenous fatty acid for phospholipid synthesis while degrading the remainder to acetyl-CoA. To a degree, the bacterium could both have its cake (the acyl chains for phospholipid synthesis) and eat it (to form acetyl-CoA). This scenario turns out to be true in E. coli. The key player in this regulatory gambit is FadR, a transcription factor that acts both as a repressor of the fatty acid degradation and as an activator of fatty acid biosynthesis.