DOI QR코드

DOI QR Code

C-Glycoside-Metabolizing Human Gut Bacterium, Dorea sp. MRG-IFC3

  • Huynh Thi Ngoc Mi (Metalloenzyme Research Group and Department of Plant Science and Technology, Chung-Ang University) ;
  • Santipap Chaiyasarn (Metalloenzyme Research Group and Department of Plant Science and Technology, Chung-Ang University) ;
  • Heji Kim (Metalloenzyme Research Group and Department of Plant Science and Technology, Chung-Ang University) ;
  • Jaehong Han (Metalloenzyme Research Group and Department of Plant Science and Technology, Chung-Ang University)
  • Received : 2023.08.14
  • Accepted : 2023.09.04
  • Published : 2023.12.28

Abstract

Biochemical gut metabolism of dietary bioactive compounds is of great significance in elucidating health-related issues at the molecular level. In this study, a human gut bacterium cleaving C-C glycosidic bond was screened from puerarin conversion to daidzein, and a new, gram-positive C-glycoside-deglycosylating strain, Dorea sp. MRG-IFC3, was isolated from human fecal sample under anaerobic conditions. Though MRG-IFC3 biotransformed isoflavone C-glycoside, it could not metabolize other C-glycosides, such as vitexin, bergenin, and aloin. As evident from the production of the corresponding aglycons from various 7-O-glucosides, MRG-IFC3 strain also showed 7-O-glycoside cleavage activity; however, flavone 3-O-glucoside icariside II was not metabolized. In addition, for mechanism study, C-glycosyl bond cleavage of puerarin by MRG-IFC3 strain was performed in D2O GAM medium. The complete deuterium enrichment on C-8 position of daidzein was confirmed by 1H NMR spectroscopy, and the result clearly proved for the first time that daidzein is produced from puerarin. Two possible reaction intermediates, the quinoids and 8-dehydrodaidzein anion, were proposed for the production of daidzein-8d. These results will provide the basis for the mechanism study of stable C-glycosidic bond cleavage at the molecular level.

Keywords

Acknowledgement

This research was supported by the Chung-Ang University Young Scientist Scholarship in 2020 and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A2C2007712).

References

  1. Hafizur M, Ansari R, Saher S, Parveen R, Khan W, Khan IA, et al. 2023. Role of gut microbiota metabolism and biotransformation on dietary natural products to human health implications with special reference to biochemoinformatics approach. J. Trad. Comp. Med. 13: 150-160. https://doi.org/10.1016/j.jtcme.2022.03.005
  2. Han J. 2019. Chemical aspects of gut metabolism of flavonoids. Metabolites 9: 136.
  3. Yang Y, Yu B. 2017. Recent advances in the chemical synthesis of C-glycosides. Chem. Rev. 117: 12281-12356. https://doi.org/10.1021/acs.chemrev.7b00234
  4. de Matos AM, Martins A, Man T, Evans D, Walter M, Oliveira MC, et al. 2019. Design and synthesis of CNS-targeted flavones and analogues with neuroprotective potential against H2O2- and Aβ1-42-induced toxicity in SH-SY5Y human neuroblastoma cells. Pharmaceuticals 12: 98.
  5. de Matos AM, Blazquez-Sanchez MT, Bento-Oliveira A, de Almeida FMR, Nunes R, Lopes PEM, et al. 2020. Glucosylpolyphenols as inhibitors of aβ-induced Fyn kinase activation and tau phosphorylation: synthesis, membrane permeability, and exploratory target assessment within the scope of type 2 diabetes and Alzheimer's disease. J. Med. Chem. 63: 11663-11690. https://doi.org/10.1021/acs.jmedchem.0c00841
  6. Jesus AR, Dias C, Mato AM, de Almeida RFM, Viana AS, Marcelo F, et al. 2014. Exploiting the therapeutic potential of 8-β-d-glucopyranosylgenistein: synthesis, antidiabetic activity, and molecular interaction with islet amyloid polypeptide and amyloid β-peptide (1-42). J. Med. Chem. 57: 9463-9472. https://doi.org/10.1021/jm501069h
  7. Wei B, Wang YK, Qiu WH, Wang SJ, Wu YH, Xu XW, et al. 2020. Discovery and mechanism of intestinal bacteria in enzymatic cleavage of C-C glycosidic bonds. Appl. Microbiol. Biotechnol. 104: 1883-1890. https://doi.org/10.1007/s00253-019-10333-z
  8. Akao T, Che Q, Kobashi K, Hattori M, Namba T. 1996. A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodinanthrone. Biol. Pharm. Bull. 19: 136-138. https://doi.org/10.1248/bpb.19.136
  9. Hasanah U, Miki K, Nitoda T, Kanzaki H. 2021. Aerobic bioconversion of C-glycoside mangiferin into its aglycone norathyriol by an isolated mouse intestinal bacterium. Biosci. Biotechnol. Biochem. 85: 989-997. https://doi.org/10.1093/bbb/zbaa121
  10. Kumano T, Hori S, Watanabe S, Kobayashi M. 2021. FAD-dependent C-glycoside-metabolizing enzymes in microorganisms: screening, characterization, and crystal structure analysis. Proc. Natl. Acad. Sci. USA 118: e2106580118.
  11. Kim M, Lee J, Han J. 2015. Deglycosylation of isoflavone C-glycosides by newly isolated human intestinal bacteria. J. Sci. Food Agric. 95: 1925-1931. https://doi.org/10.1002/jsfa.6900
  12. Braune A, Blaut M. 2011. Deglycosylation of puerarin and other aromatic C-glucosides by a newly isolated human intestinal bacterium. Environ. Microbiol. 13: 482-494. https://doi.org/10.1111/j.1462-2920.2010.02352.x
  13. Zheng S, Geng D, Liu S, Wang R. 2019. A newly isolated human intestinal bacterium strain capable of deglycosylating flavone C-glycosides and its functional properties. Microb. Cell Fact. 18: 94.
  14. Nakamura K, Nishihata T, Jin JS, Ma CM, Komatsu K, Iwashima M, et al. 2011. The C-glucosyl bond of puerarin was cleaved hydrolytically by a human intestinal bacterium strain PUE to yield its aglycone daidzein and an intact glucose. Chem. Pharm. Bull. 59: 23-27. https://doi.org/10.1248/cpb.59.23
  15. Xu J, Qian D, Jiang S, Guo J, Shang E, Duan J, et al. 2014. Application of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to determine the metabolites of orientin produced by human intestinal bacteria. J. Chromatogr. B. 944: 123-127. https://doi.org/10.1016/j.jchromb.2013.11.002
  16. Sanugul K, Akao T, Li Y, Kakiuchi N, Nakamura N, Hattori M. 2005. Isolation of a human intestinal bacterium that transforms mangiferin to norathyriol and inducibility of the enzyme that cleaves a C-glucosyl bond. Biol. Pharm. Bull. 28: 1672-1678. https://doi.org/10.1248/bpb.28.1672
  17. Nakamura K, Zhu S, Komatsu K, Hattori M, Iwashima M. 2020. Deglycosylation of the isoflavone C-glucoside puerarin by a combination of two recombinant bacterial enzymes and 3-oxo-glucose. Appl. Environ. Microbiol. 86: e00607-20. https://doi.org/10.1128/AEM.00607-20
  18. Braune A, Engst W, Blaut M. 2016. Identification and functional expression of genes encoding flavonoid O- and C-glycosidases in intestinal bacteria. Environ. Microbiol. 18: 2117-2129. https://doi.org/10.1111/1462-2920.12864
  19. Mori T, Kumano T, He H, Watanabe S, Senda M, Moriya T, et al. 2021. C-Glycoside metabolism in the gut and in nature: identification, characterization, structural analyses and distribution of C-C bond-cleaving enzymes. Nat. Commun. 12: 6294.
  20. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J. Mol. Biol. 215: 403-410. https://doi.org/10.1016/S0022-2836(05)80360-2
  21. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. 2018. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol. Biol. Evol. 35: 1547-1549. https://doi.org/10.1093/molbev/msy096
  22. Zhang Z, Schwartz S, Wagner L, Miller W. 2000. A greedy algorithm for aligning DNA sequences. J. Comput. Biol. 7: 203-214. https://doi.org/10.1089/10665270050081478
  23. Burapan S, Kim M, Han J. 2017. Demethylation of polymethoxyflavones by human gut bacterium, Blautia sp. MRG-PMF1. J. Agric. Food Chem. 65: 1620-1629. https://doi.org/10.1021/acs.jafc.7b00408
  24. Wu H, Kim M, Han J. 2016. Icariin metabolism by human intestinal microflora. Molecules 21: 1158.
  25. Mi HTN, Chaiyasarn S, Eser BE, Tan SRS, Burapan S, Han J. 2022. Allyl aryl ether cleavage by Blautia sp. MRG-PMF1 Co corrinoid O-demethylase. Microbiol. Spectr. 10: e0330522.
  26. Burapan S, Kim M, Han J. 2017. Curcuminoid demethylation as an alternative metabolism by human intestinal microbiota. J. Agric. Food Chem. 65: 3305-3310. https://doi.org/10.1021/acs.jafc.7b00943
  27. Burapan S, Kim M, Paisooksantivatana Y, Eser BE, Han J. 2020. Thai Curcuma Species: antioxidant and bioactive compounds. Foods 9: 1219.