Bipin Rimal, Stephanie L Collins, Ceylan E Tanes, Edson R Rocha, Megan A Granda, Sumeet Solanki, Nushrat J Hoque, Emily C Gentry, Imhoi Koo, Erin R Reilly, Fuhua Hao, Devendra Paudel, Vishal Singh, Tingting Yan, Min Soo Kim, Kyle Bittinger, Joseph P Zackular, Kristopher W Krausz, Dhimant Desai, Shantu Amin, James P Coleman, Yatrik M Shah, Jordan E Bisanz, Frank J Gonzalez, John P Vanden Heuvel, Gary D Wu, Babette S Zemel, Pieter C Dorrestein, Emily E Weinert, Andrew D Patterson
Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6 ; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs...
February 7, 2024: Nature