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Microbiology and Biotechnology Letters

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Environmental Microbiology (EM)  |  Microbial Ecology and Diversity

Microbiol. Biotechnol. Lett. 2022; 50(1): 102-109

https://doi.org/10.48022/mbl.2111.11010

Received: November 16, 2021; Revised: January 11, 2022; Accepted: January 19, 2022

Challenging the Hypothesis of de novo Biosynthesis of Bile Acids by Marine Bacteria

Felipe Gonzalo Tueros1, Mostafa M. Hashim Ellabaan1, Marcus Henricsson2, Ruben Vazquez-Uribe1, Fredrik Bäckhed2, and Morten Otto Alexander Sommer1*

1Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby 2800, Denmark 2Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg 41345, Sweden

Correspondence to :
Morten Otto Alexander Sommer,        msom@biosustain.dtu.dk

Bile acids are essential molecules produced by vertebrates that are involved in several physiological roles, including the uptake of nutrients. Bacterial isolates capable of producing bile acids de novo have been identified and characterized. Such isolates may provide access to novel biochemical pathways suitable for the design of microbial cell factories. Here, we further characterized the ability of Maribacter dokdonensis, Dokdonia donghaensis, and Myroides pelagicus to produce bile acids. Contrary to previous reports, we did not observe de novo production of bile acids by these isolates. Instead, we found that these isolates deconjugated the amino acid moiety of bile acids present in the growth medium used in previous reports. Through genomic analysis, we identified putative bile salt hydrolases, which could be responsible for the different bile acid modifications observed. Our results challenge the hypothesis of de novo microbial bile acid production, while further demonstrating the diverse capacity of bacteria to modify bile acids.

Keywords: Bile acids, bile salt hydrolase, marine bacteria, bile acid modification, bile acid production

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  1. Hofmann AF, Hagey LR, Krasowski MD. 2010. Bile salts of vertebrates:structural variation and possible evolutionary significance. J. Lipid Res. 51: 226-246.
    Pubmed KoreaMed
  2. Hofmann AF, Hagey LR. 2008. Review bile acids: Chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell. Mol. Life Sci. 65: 2461-2483.
    Pubmed
  3. Foley MH, Flaherty SO, Barrangou R, Theriot CM. 2019. Bile salt hydrolases: Gatekeepers of bile acid metabolism and hostmicrobiome crosstalk in the gastrointestinal tract. PLoS Pathog. 15: e1007581.
    Pubmed KoreaMed
  4. Jones BV, Begley M, Hill C, Gahan CGM, Marchesi JR. 2008. Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proc. Natl. Acad. Sci. USA 105: 13580-13585.
    Pubmed KoreaMed
  5. Russell DW, Setchell KDR. 1992. Bile acid biosynthesis. Biochemistry 31: 4737-4749.
    Pubmed
  6. Hofmann AF. 1999. The continuing importance of bile acids in liver and intestinal disease. Arch. Intern. Med. 159: 2647-2658.
    Pubmed
  7. Bowlus CL. 2016. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection. Hepat. Med. 8: 89-95.
    Pubmed KoreaMed
  8. Kim DJ, Yoon S, Ji SC, Yang J, Kim YK, Lee S, et al. 2018. Ursodeoxycholic acid improves liver function via phenylalanine/tyrosine pathway and microbiome remodelling in patients with liver dysfunction. Sci. Rep. 8: 11874.
    Pubmed KoreaMed
  9. Passed A, Lang S, Wagner F, Wray V. 1991. Anionic trehalose tetraester from the marine bacterium Arthrobacter sp. EK 1. Naturforsch 46c: 204-209.
    Pubmed
  10. Maneerat S, Nitoda T, Kanzaki H, Kawai F. 2005. Bile acids are new products of a marine bacterium, Myroides sp. strain SM1. Appl. Microbiol. Cell Physiol. 67: 679-683.
    Pubmed
  11. Kim D, Kim J, Kang SJ, Yoon JH, Kim WG, Lee JS, et al. 2007. Biosynthesis of bile acids in a variety of marine bacteria taxa. J. Microbiol. Biotechnol. 17: 403-407.
  12. Tremaroli V, Karlsson F, Werling M, St?hlman M, KovatchevaDatchary P, Olbers T, et al. 2015. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 22: 228-238.
    Pubmed KoreaMed
  13. Tatusov RL, Galperin MY, Natale DA, Koonin EV. 2000. The COG database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids Res. 28: 33-36.
    Pubmed KoreaMed
  14. Besemer J, Lomsadze A, Borodovsky M. 2001. GeneMarkS: a selftraining method for prediction of gene starts in microbial genomes. Implications for finding sequence motifs in regulatory regions. Nucleic Acids Res. 29: 2607-2618.
    Pubmed KoreaMed
  15. Madeira F, Park YM, Lee J, Buso N, Gur T, Madhusoodanan N, et al. 2019. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res. 47: W636-W641.
    Pubmed KoreaMed
  16. Price MN, Dehal PS, Arkin AP. 2009. FastTree: Computing large minimum-evolution trees with profiles instead of a distance matrix. Mol. Biol. Evol. 26: 1641-1650.
    Pubmed KoreaMed
  17. Ohashi K, Miyagawa Y, Nakamura Y, Shibuya H. 2008. Bioproduction of bile acids and the glycine conjugates by Penicillium fungus. J. Nat. Med. 62: 83-86.
    Pubmed
  18. Park SC, Kim CJ, Uramoto M, Yun HI, Yoon KH, Oh TK. 1995. Antibacterial substance produced by Streptococcus faecium under anaerobic culture. Biosci. Biotechnol. Biochem. 59: 1966-1967.
    Pubmed
  19. Hill C, Gahan CGM. 2006. Bile salt hydrolase activity in probiotics. Appl. Environ. Microbiol. 72: 1729-1738.
    Pubmed KoreaMed
  20. Panigrahi P, Sule M, Sharma R, Ramasamy S, Suresh, CG. 2014. An improved method for specificity annotation shows a distinct evolutionary divergence among the microbial enzymes of the cholylglycine hydrolase family. Microbiology 160: 1162-1174.
    Pubmed
  21. Valle F, Balb?s P, Merino E, Bollvar F. 1991. The role of penicillin amidases in nature and in industry. Trends Biochem. Sci. 16: 3640.
  22. Kim SH, Yang HO, Sohn YC, Kwon HC. 2010. Aeromicrobium halocynthiae sp. nov., a taurocholic acid-producing bacterium isolated from the marine ascidian Halocynthia roretzi. Int. J. Syst. Evol. Microbiol. 60: 2793-2798.
    Pubmed
  23. Li H, Shinde PB, Lee HJ, Yoo ES, Hong J, Choi SH, et al. 2009. Bile acid derivatives from a sponge-associated bacterium. Arch. Pharm. Res. 32: 857-862.
    Pubmed
  24. Kim SH, Yang HO, Shin YK, Kwon HC. 2012. Hasllibacter halocynthiae gen. nov., sp. nov., a nutriacholic acid-producing bacterium isolated from the marine ascidian Halocynthia roretzi. Int. J. Syst. Evol. Microbiol. 62: 624-631.
    Pubmed

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