The bile acid-CoA ligase, FATP5, is necessary for the synthesis of N-acyl taurines in the liver.

N-acyl taurines (NAT) are endogenous, bioactive conjugates of fatty acids and taurine with roles in carbohydrate and lipid metabolism. In the liver, NATs are synthesized by bile acid-CoA:amino acid N-acyltransferase (BAAT), which also conjugates bile acids to taurine or glycine, suggesting an overlapping hepatic synthesis pathway. BAAT catalyzes the transfer of an acyl-chain from an activated coenzyme A (CoA) to taurine, but the hepatic enzyme responsible for synthesizing the acyl-CoA remains unknown. Using liver transcriptomics in mice unable to hydrolyze NATs, we identified Slc27a5, which encodes the acyl-CoA synthetase, fatty acid transport protein 5 (FATP5), as a potential regulator of hepatic NAT synthesis. In vivo knockdown of the enzyme confirmed that FATP5 is necessary for hepatic NAT synthesis and upstream of BAAT, likely through its acyl-CoA synthetase activity. The dual function of this enzyme in activating both fatty acids and bile acids for conjugation identifies a functional overlap between the hepatic NAT and bile acid production pathway.