BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe Clostridium scindens ATCC 35704

ABSTRACTBile acid transformation is a common gut microbiome activity that produces secondary bile acids, some of which are important for human health. One such process, 7α-dehydroxylation, converts the primary bile acids, cholic acid and chenodeoxycholic acid, to deoxycholic acid and lithocholic aci...

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Main Authors: Karin Lederballe Meibom, Solenne Marion, Colin Volet, Théo Nass, Eduard Vico-Oton, Laure Menin, Rizlan Bernier-Latmani
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Gut Microbes
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2024.2323233
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author Karin Lederballe Meibom
Solenne Marion
Colin Volet
Théo Nass
Eduard Vico-Oton
Laure Menin
Rizlan Bernier-Latmani
author_facet Karin Lederballe Meibom
Solenne Marion
Colin Volet
Théo Nass
Eduard Vico-Oton
Laure Menin
Rizlan Bernier-Latmani
author_sort Karin Lederballe Meibom
collection DOAJ
description ABSTRACTBile acid transformation is a common gut microbiome activity that produces secondary bile acids, some of which are important for human health. One such process, 7α-dehydroxylation, converts the primary bile acids, cholic acid and chenodeoxycholic acid, to deoxycholic acid and lithocholic acid, respectively. This transformation requires a number of enzymes, generally encoded in a bile acid-inducible (bai) operon and consists of multiple steps. Some 7α-dehydroxylating bacteria also harbor additional genes that encode enzymes with potential roles in this pathway, but little is known about their functions. Here, we purified 11 enzymes originating either from the bai operon or encoded at other locations in the genome of Clostridium scindens strain ATCC 35704. Enzyme activity was probed in vitro under anoxic conditions to characterize the biochemical pathway of chenodeoxycholic acid 7α-dehydroxylation. We found that more than one combination of enzymes can support the process and that a set of five enzymes, including BaiJ that is encoded outside the bai operon, is sufficient to achieve the transformation. We found that BaiJ, an oxidoreductase, exhibits an activity that is not harbored by the homologous enzyme from another C. scindens strain. Furthermore, ligation of bile acids to coenzyme A (CoA) was shown to impact the product of the transformation. These results point to differences in the 7α-dehydroxylation pathway among microorganisms and the crucial role of CoA ligation in the process.
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spelling doaj.art-3e999888086e4cc2927ab2b71429a4c22024-03-11T10:23:24ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2323233BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe Clostridium scindens ATCC 35704Karin Lederballe Meibom0Solenne Marion1Colin Volet2Théo Nass3Eduard Vico-Oton4Laure Menin5Rizlan Bernier-Latmani6Environmental Microbiology Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandEnvironmental Microbiology Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandEnvironmental Microbiology Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandEnvironmental Microbiology Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandEnvironmental Microbiology Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandInstitute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandEnvironmental Microbiology Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandABSTRACTBile acid transformation is a common gut microbiome activity that produces secondary bile acids, some of which are important for human health. One such process, 7α-dehydroxylation, converts the primary bile acids, cholic acid and chenodeoxycholic acid, to deoxycholic acid and lithocholic acid, respectively. This transformation requires a number of enzymes, generally encoded in a bile acid-inducible (bai) operon and consists of multiple steps. Some 7α-dehydroxylating bacteria also harbor additional genes that encode enzymes with potential roles in this pathway, but little is known about their functions. Here, we purified 11 enzymes originating either from the bai operon or encoded at other locations in the genome of Clostridium scindens strain ATCC 35704. Enzyme activity was probed in vitro under anoxic conditions to characterize the biochemical pathway of chenodeoxycholic acid 7α-dehydroxylation. We found that more than one combination of enzymes can support the process and that a set of five enzymes, including BaiJ that is encoded outside the bai operon, is sufficient to achieve the transformation. We found that BaiJ, an oxidoreductase, exhibits an activity that is not harbored by the homologous enzyme from another C. scindens strain. Furthermore, ligation of bile acids to coenzyme A (CoA) was shown to impact the product of the transformation. These results point to differences in the 7α-dehydroxylation pathway among microorganisms and the crucial role of CoA ligation in the process.https://www.tandfonline.com/doi/10.1080/19490976.2024.2323233Clostridium scindensbile acids7α-dehydroxylationgut microbesbai geneschenodeoxycholic acid
spellingShingle Karin Lederballe Meibom
Solenne Marion
Colin Volet
Théo Nass
Eduard Vico-Oton
Laure Menin
Rizlan Bernier-Latmani
BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe Clostridium scindens ATCC 35704
Gut Microbes
Clostridium scindens
bile acids
7α-dehydroxylation
gut microbes
bai genes
chenodeoxycholic acid
title BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe Clostridium scindens ATCC 35704
title_full BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe Clostridium scindens ATCC 35704
title_fullStr BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe Clostridium scindens ATCC 35704
title_full_unstemmed BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe Clostridium scindens ATCC 35704
title_short BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe Clostridium scindens ATCC 35704
title_sort baij and baib are key enzymes in the chenodeoxycholic acid 7α dehydroxylation pathway in the gut microbe clostridium scindens atcc 35704
topic Clostridium scindens
bile acids
7α-dehydroxylation
gut microbes
bai genes
chenodeoxycholic acid
url https://www.tandfonline.com/doi/10.1080/19490976.2024.2323233
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