2024-02-28 ペンシルベニア州立大学(PennState)
<関連情報>
- https://www.psu.edu/news/agricultural-sciences/story/new-role-bacterial-enzyme-gut-metabolism-revealed/
- https://www.nature.com/articles/s41586-023-06990-w
胆汁酸塩加水分解酵素がアミン共役胆汁酸の生成を触媒することが判明 Bile salt hydrolase catalyses formation of amine-conjugated bile acids
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,… Andrew D. Patterson
Nature Published:07 February 2024
DOI:https://doi.org/10.1038/s41586-023-06990-w
Abstract
Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1,2,3,4,5,6; 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. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.
