Decoding the Promiscuous Activity of Bile Salt Hydrolase

The recently identified bile salt hydrolase (BSH) from gastrointestinal bacteria catalyzes the formation of bacterial bile acid amidates (BBAAs), significantly impacting host metabolism. While this activity was characterized as promiscuous, the underlying mechanism was not explored. This commentary proposes that BSH exhibits condition promiscuity, where typical hydrolytic enzymes catalyze synthetic reactions under specific conditions. Drawing parallels with micellar enzymology, we suggest that bile salts, acting as both substrates and micelle-forming agents, create an environment conducive for BSH to catalyze amidation. This represents a potential first in vivo demonstration of such a mechanism. Future investigations should explore BSH-catalyzed reactions with bile salts below critical micelle concentrations and alternative surfactants to validate this hypothesis.