The Bacteroidales produce an N-acylated derivative of glycine with both cholesterol-solubilising and hemolytic activity

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Date
2017
Authors
Lynch, Alli
Crowley, Elaine
Casey, Eoghan
Cano, Rafael
Shanahan, Rachel
McGlacken, Gerard P.
Marchesi, Julian R.
Clarke, David J.
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Nature Publishing Group
Published Version
10.1038/s41598-017-13774-6
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Abstract
The contribution of the gut microbiota to the metabolism of cholesterol is not well understood. In this study, we identify 21 fosmid clones from a human gut microbiome metagenomic library that, when expressed in Escherichia coli, produce halos on LB agar supplemented with 0.01% (w/v) cholesterol (LBC agar). Analysis of 14 of these clones revealed that they all share a fragment of DNA with homology to the genome of Bacteroides vulgatus. The gene responsible for halo production on LBC agar, named choA, was identified as an N-acyltransferase known to produce an acylated glycine molecule called commendamide. In this study we show that commendamide is capable of producing a halo on LBC agar suggesting that this molecule is solubilizing the cholesterol micelles in LBC agar. We also show that commendamide is responsible for the previously described hemolytic activity associated with the choA orthologue in Bacteroides fragilis. A functional analysis of ChoA identified 2 amino acids that are important for commendamide biosynthesis and we present phylogenetic and functional data showing that orthologues of choA are found only in the order Bacteroidales. Therefore, the production of commendamide may be an adaptation to the environments colonized by the Bacteroidales, including the mammalian gut.
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Keywords
Human gut microbiome , Eubacterium-coprostanoligenes , Fragilis hemolysins , Environmental DNA , Escherichia-coli , Identification , Biosynthesis , Expression , Bacterium , Lipids
Citation
Lynch, A., Crowley, E., Casey, E., Cano, R., Shanahan, R., McGlacken, G., Marchesi, J. R. and Clarke, D. J. (2017) 'The Bacteroidales produce an N-acylated derivative of glycine with both cholesterol-solubilising and hemolytic activity', Scientific Reports, 7(1), 13270 (10pp). doi: 10.1038/s41598-017-13774-6
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https://www.nature.com/articles/s41598-017-13774-6
URI
https://hdl.handle.net/10468/6349
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Microbiology - Journal Articles
APC Microbiome Ireland - Journal Articles
Chemistry - Journal Articles
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© 2017, the Authors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.