Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes
The gut microbiome of vertebrates is capable of numerous biotransformations of bile acids, which are responsible for intestinal lipid digestion and function as key nutrient-signaling molecules. The human liver produces bile acids from cholesterol predominantly in the A/B-cis orientation in which the...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2132903 |
| _version_ | 1818468937054027776 |
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| author | Jae Won Lee Elise S. Cowley Patricia G. Wolf Heidi L. Doden Tsuyoshi Murai Kelly Yovani Olivos Caicedo Lindsey K. Ly Furong Sun Hajime Takei Hiroshi Nittono Steven L. Daniel Isaac Cann H. Rex Gaskins Karthik Anantharaman João M. P. Alves Jason M. Ridlon |
| author_facet | Jae Won Lee Elise S. Cowley Patricia G. Wolf Heidi L. Doden Tsuyoshi Murai Kelly Yovani Olivos Caicedo Lindsey K. Ly Furong Sun Hajime Takei Hiroshi Nittono Steven L. Daniel Isaac Cann H. Rex Gaskins Karthik Anantharaman João M. P. Alves Jason M. Ridlon |
| author_sort | Jae Won Lee |
| collection | DOAJ |
| description | The gut microbiome of vertebrates is capable of numerous biotransformations of bile acids, which are responsible for intestinal lipid digestion and function as key nutrient-signaling molecules. The human liver produces bile acids from cholesterol predominantly in the A/B-cis orientation in which the sterol rings are “kinked”, as well as small quantities of A/B-trans oriented “flat” stereoisomers known as “primary allo-bile acids”. While the complex multi-step bile acid 7α-dehydroxylation pathway has been well-studied for conversion of “kinked” primary bile acids such as cholic acid (CA) and chenodeoxycholic acid (CDCA) to deoxycholic acid (DCA) and lithocholic acid (LCA), respectively, the enzymatic basis for the formation of “flat” stereoisomers allo-deoxycholic acid (allo-DCA) and allo-lithocholic acid (allo-LCA) by Firmicutes has remained unsolved for three decades. Here, we present a novel mechanism by which Firmicutes generate the ”flat” bile acids allo-DCA and allo-LCA. The BaiA1 was shown to catalyze the final reduction from 3-oxo-allo-DCA to allo-DCA and 3-oxo-allo-LCA to allo-LCA. Phylogenetic and metagenomic analyses of human stool samples indicate that BaiP and BaiJ are encoded only in Firmicutes and differ from membrane-associated bile acid 5α-reductases recently reported in Bacteroidetes that indirectly generate allo-LCA from 3-oxo-Δ4-LCA. We further map the distribution of baiP and baiJ among Firmicutes in human metagenomes, demonstrating an increased abundance of the two genes in colorectal cancer (CRC) patients relative to healthy individuals. |
| first_indexed | 2024-04-13T21:18:17Z |
| format | Article |
| id | doaj.art-0b07c4b640f44f539dde1e5c2357624f |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-04-13T21:18:17Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-0b07c4b640f44f539dde1e5c2357624f2022-12-22T02:29:36ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2132903Formation of secondary allo-bile acids by novel enzymes from gut FirmicutesJae Won Lee0Elise S. Cowley1Patricia G. Wolf2Heidi L. Doden3Tsuyoshi Murai4Kelly Yovani Olivos Caicedo5Lindsey K. Ly6Furong Sun7Hajime Takei8Hiroshi Nittono9Steven L. Daniel10Isaac Cann11H. Rex Gaskins12Karthik Anantharaman13João M. P. Alves14Jason M. Ridlon15Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USADepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USACarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USACarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USASchool of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, JapanDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilCarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USAMass Spectrometry Laboratory, School of Chemical Sciences, University of Illinois Urbana-Champaign, IL, USAJunshin Clinic Bile Acid Institute, Tokyo, JapanJunshin Clinic Bile Acid Institute, Tokyo, JapanDepartment of Biological Sciences, Eastern Illinois University, Charleston, IL, USACarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USACarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USADepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USADepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilCarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USAThe gut microbiome of vertebrates is capable of numerous biotransformations of bile acids, which are responsible for intestinal lipid digestion and function as key nutrient-signaling molecules. The human liver produces bile acids from cholesterol predominantly in the A/B-cis orientation in which the sterol rings are “kinked”, as well as small quantities of A/B-trans oriented “flat” stereoisomers known as “primary allo-bile acids”. While the complex multi-step bile acid 7α-dehydroxylation pathway has been well-studied for conversion of “kinked” primary bile acids such as cholic acid (CA) and chenodeoxycholic acid (CDCA) to deoxycholic acid (DCA) and lithocholic acid (LCA), respectively, the enzymatic basis for the formation of “flat” stereoisomers allo-deoxycholic acid (allo-DCA) and allo-lithocholic acid (allo-LCA) by Firmicutes has remained unsolved for three decades. Here, we present a novel mechanism by which Firmicutes generate the ”flat” bile acids allo-DCA and allo-LCA. The BaiA1 was shown to catalyze the final reduction from 3-oxo-allo-DCA to allo-DCA and 3-oxo-allo-LCA to allo-LCA. Phylogenetic and metagenomic analyses of human stool samples indicate that BaiP and BaiJ are encoded only in Firmicutes and differ from membrane-associated bile acid 5α-reductases recently reported in Bacteroidetes that indirectly generate allo-LCA from 3-oxo-Δ4-LCA. We further map the distribution of baiP and baiJ among Firmicutes in human metagenomes, demonstrating an increased abundance of the two genes in colorectal cancer (CRC) patients relative to healthy individuals.https://www.tandfonline.com/doi/10.1080/19490976.2022.2132903Secondary allo-bile acidsbile acid dehydroxylationbile acid 5α-reductasesFirmicutescolorectal cancer |
| spellingShingle | Jae Won Lee Elise S. Cowley Patricia G. Wolf Heidi L. Doden Tsuyoshi Murai Kelly Yovani Olivos Caicedo Lindsey K. Ly Furong Sun Hajime Takei Hiroshi Nittono Steven L. Daniel Isaac Cann H. Rex Gaskins Karthik Anantharaman João M. P. Alves Jason M. Ridlon Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes Gut Microbes Secondary allo-bile acids bile acid dehydroxylation bile acid 5α-reductases Firmicutes colorectal cancer |
| title | Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes |
| title_full | Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes |
| title_fullStr | Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes |
| title_full_unstemmed | Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes |
| title_short | Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes |
| title_sort | formation of secondary allo bile acids by novel enzymes from gut firmicutes |
| topic | Secondary allo-bile acids bile acid dehydroxylation bile acid 5α-reductases Firmicutes colorectal cancer |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2132903 |
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