A Novel Gene Alignment in Dorea sp. AM58‑8 Produces 7‑Dehydroxy-3β Bile Acids from Primary Bile Acids

Yingjie Bai, Tianhu Zhao, Mengyu Gao, Yuanqiang Zou, and Xiaoguang Lei*

https://doi.org/10.1021/acs.biochem.2c00264

Special Issue: Microbiome
Received: May 8, 2022
Revised: September 2, 2022

Bile acids are essential metabolites and signaling molecules in mammals. Primary bile acids are synthesized from cholesterol in the liver. At the same time, the microbiota in the mammalian gut has many interactions with bile acid, including various biotransformation processes such as 7-dehydroxylation and 3- epimerization. 7-Dehydroxylation is mediated by a bile acid-inducible (bai) operon, while 7-dehydroxylation and 3-epimerization are independently observed in only a few strains. Herein, we describe a novel microbe, Dorea sp. AM58-8, that can accomplish a two-steptransformation and turn primary bile acids into both 3α secondary bile acids like deoxycholic acid and lithocholic acid, and 3β secondary bile acids like isodeoxycholic acid and isolithocholic acid. We subsequently characterized BaiA, BaiB, BaiE, and their substrate profiles biochemically. The potential bai gene clusters in the metagenomes were further mined. Their evolution, potential functions, and possible regulatory pathways were predicted using bioinformatics based on our understanding of the 7-dehydroxylation pathway in Dorea sp. AM58-8. This study of Dorea sp. AM58-8 also helps us distinguish the inactive bacteria that seem to have the 7- dehydroxylation pathway proteins and discover the 7-dehydroxylation pathway in other mammalian gut microbes.

Yingjie Bai, Tianhu Zhao, Mengyu Gao, Yuanqiang Zou, and Xiaoguang Lei*

https://doi.org/10.1021/acs.biochem.2c00264

Special Issue: Microbiome
Received: May 8, 2022
Revised: September 2, 2022

Bile acids are essential metabolites and signaling molecules in mammals. Primary bile acids are synthesized from cholesterol in the liver. At the same time, the microbiota in the mammalian gut has many interactions with bile acid, including various biotransformation processes such as 7-dehydroxylation and 3- epimerization. 7-Dehydroxylation is mediated by a bile acid-inducible (bai) operon, while 7-dehydroxylation and 3-epimerization are independently observed in only a few strains. Herein, we describe a novel microbe, Dorea sp. AM58-8, that can accomplish a two-steptransformation and turn primary bile acids into both 3α secondary bile acids like deoxycholic acid and lithocholic acid, and 3β secondary bile acids like isodeoxycholic acid and isolithocholic acid. We subsequently characterized BaiA, BaiB, BaiE, and their substrate profiles biochemically. The potential bai gene clusters in the metagenomes were further mined. Their evolution, potential functions, and possible regulatory pathways were predicted using bioinformatics based on our understanding of the 7-dehydroxylation pathway in Dorea sp. AM58-8. This study of Dorea sp. AM58-8 also helps us distinguish the inactive bacteria that seem to have the 7- dehydroxylation pathway proteins and discover the 7-dehydroxylation pathway in other mammalian gut microbes.