1887

Abstract

-Glucuronidase activity (encoded by the gene) has been characterized for the first time from E1, an anaerobic bacterium belonging to the dominant human gut microbiota. -Glucuronidase activity plays a major role in the generation of toxic and carcinogenic metabolites in the large intestine, as well as in the absorption and enterohepatic circulation of many aglycone residues with protective effects, such as lignans, flavonoids, ceramide and glycyrrhetinic acid, that are liberated by the hydrolysis of the corresponding glucuronides. The complete nucleotide sequence of a 4537 bp DNA fragment containing the -glucuronidase locus from E1 was determined. Five ORFs were detected on this fragment: three complete ORFs (ORF2, and ORF3) and two partial ORFs (ORF4 and ORF5). The products of ORF2 and ORF3 show strong similarities with many -glucoside permeases of the phosphoenolpyruvate : -glucoside phosphotransferase systems (PTSs), such as BglC, BglP and PTS Enzyme II. The product of ORF5 presents strong similarities with the amino-terminal domain of -glucosidase (). The gene product presents similarities with several known -glucuronidase enzymes, including those of (69 %), (61 %), (59 %) and (58 %). By complementing an strain in which the gene encoding the enzyme was deleted, it was confirmed that the gene encodes the -glucuronidase enzyme. Moreover, it was found that the gene was transcribed as part of an operon that includes ORF2, ORF3 and ORF5.

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2005-07-01
2019-10-17
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References

  1. Akao, T. ( 1999; ). Purification and characterization of glycyrrhetic acid monoglucuronide beta-d-glucuronidase in Eubacterium sp. GLH. Biol Pharm Bull 22, 80–82.[CrossRef]
    [Google Scholar]
  2. Akao, T. ( 2000; ). Competition in the metabolism of glycyrrhizin with glycyrrhetic acid mono-glucuronide by mixed Eubacterium sp. GLH and Ruminococcus sp. PO1-3. Biol Pharm Bull 23, 149–154.[CrossRef]
    [Google Scholar]
  3. Arimochi, H., Kataoka, K., Kuwahara, T., Nakayama, H., Misawa, N. & Ohnishi, Y. ( 1999; ). Effects of beta-glucuronidase-deficient and lycopene-producing Escherichia coli strains on formation of azoxymethane-induced aberrant crypt foci in the rat colon. Biochem Biophys Res Commun 262, 322–327.[CrossRef]
    [Google Scholar]
  4. Chen, X., Wu, B. & Wang, P. G. ( 2003; ). Glucuronides in anti-cancer therapy. Curr Med Chem C Anti-Cancer Agents 3, 139–150.[CrossRef]
    [Google Scholar]
  5. Dabard, J., Bridonneau, C., Phillipe, C. & 8 other authors ( 2001; ). Ruminococcin A, a new lantibiotic produced by a Ruminococcus gnavus strain isolated from human feces. Appl Environ Microbiol 67, 4111–4118.[CrossRef]
    [Google Scholar]
  6. Datsenko, K. A. & Wanner, B. L. ( 2000; ). One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97, 6640–6645.[CrossRef]
    [Google Scholar]
  7. De Graaf, M., Boven, F., Scheeren, H. W., Haisma, H. J. & Pinedo, H. M. ( 2002; ). Betaglucuronidase mediated drug release. Curr Pharm Des 8, 1391–1403.[CrossRef]
    [Google Scholar]
  8. Dutton, G. J. ( 1978; ). Developmental aspects of drug conjugation, with special reference to glucuronidation. Annu Rev Pharmacol Toxicol 18, 17–35.[CrossRef]
    [Google Scholar]
  9. Fujisawa, T. & Mori, M. ( 1996; ). Influence of bile salts on beta-glucuronidase activity of intestinal bacteria. Lett Appl Microbiol 22, 271–274.[CrossRef]
    [Google Scholar]
  10. Gilson, T. J. ( 1984; ). PhD thesis. University of Cambridge.
  11. Gueraud, F. & Paris, A. ( 1998; ). Glucuronidation: a dual control. Gen Pharmacol 31, 683–688.[CrossRef]
    [Google Scholar]
  12. Hawkesworth, G., Draser, B. S. & Hill, M. J. ( 1971; ). Intestinal bacteria and the hydrolysis of glycosidic bonds. J Med Microbiol 4, 451–459.[CrossRef]
    [Google Scholar]
  13. Hill, M.-J., Drasar, B. S., Hawksworth, G. & William, R. E. ( 1971; ). Bacteria and aetiology of cancer of large bowel. Lancet 1, 95–100.
    [Google Scholar]
  14. Islam, M. R., Tomatsu, S., Shah, G. N., Grubb, J. H., Jain, S. & Sly, W. S. ( 1999; ). Active site residues of human beta-glucuronidase. Evidence for Glu(540) as the nucleophile and Glu(451) as the acid–base residue. J Biol Chem 274, 23451–23455.[CrossRef]
    [Google Scholar]
  15. Jefferson, R. A. ( 1989; ). The gus reporter gene system. Nature 342, 837–838.[CrossRef]
    [Google Scholar]
  16. Jefferson, R. A., Burgess, S. M. & Hirsh, D. ( 1986; ). Beta-Glucuronidase from Escherichia coli as a gene fusion marker. Proc Natl Acad Sci U S A 83, 8447–8451.[CrossRef]
    [Google Scholar]
  17. Jenab, M., Richard, S. E., Orcheson, L. J. & Thompson, L. U. ( 1999; ). Flaxseed and lignans increase cecal betaglucuronidase activity in rats. Nutr Cancer 33, 154–158.[CrossRef]
    [Google Scholar]
  18. Jeong, H. G., You, H. J., Park, S. J., Moon, A. R., Chung, Y. C., Kang, S. K. & Chun, H. K. ( 2002; ). Hepatoprotective effects of 18beta-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: inhibition of cytochrome P450 2E1 expression. Pharmacol Res 46, 221–227.[CrossRef]
    [Google Scholar]
  19. Kim, D.-H., Jung, E. A., Sohng, I. S., Han, J. A., Kim, T. H. & Han, M. J. ( 1998; ). Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch Pharm Res 21, 17–23.[CrossRef]
    [Google Scholar]
  20. Kim, D.-H., Hong, S. W., Kim, B. T., Bae, E. A., Park, H. Y. & Han, M. J. ( 2000; ). Biotransformation of glycyrrhizin by human intestinal bacteria and its relation to biological activities. Arch Pharm Res 23, 172–173.[CrossRef]
    [Google Scholar]
  21. Kohno, H., Tanaka, T., Kawabata, K., Hirose, Y., Sugie, S., Tsuda, H. & Mori, H. ( 2002; ). Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer 101, 461–468.[CrossRef]
    [Google Scholar]
  22. Liang, W.-J., Wilson, K. J., Xie, H., Knol, J., Suzuki, S., Rutherford, N. G., Henderson, P. J. F. & Jefferson, R. A. ( 2005; ). The gusBC genes of Escherichia coli encode a glucuronide transport system. J Bacteriol 187, 2377–2385.[CrossRef]
    [Google Scholar]
  23. Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. ( 1951; ). Protein measurement with the Folin phenol reagent. J Biol Chem 193, 265–275.
    [Google Scholar]
  24. McBain, A. J. & Macfarlane, G. T. ( 1998; ). Ecological and physiological studies on large intestinal bacteria in relation to production of hydrolytic and reductive enzymes involved in formation of genotoxic metabolites. J Med Microbiol 47, 407–416.[CrossRef]
    [Google Scholar]
  25. Nelson, K. E. R. A., Clayton, S. R., Gill, M. L. & 26 other authors ( 1999; ). Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima. Nature 399, 323–329.[CrossRef]
    [Google Scholar]
  26. Novel, M. & Novel, G. ( 1976; ). Regulation of beta-glucuronidase synthesis in Escherichia coli K-12: constitutive mutants specifically derepressed for uidA expression. J Bacteriol 127, 406–417.
    [Google Scholar]
  27. Ramare, F., Nicoli, J., Dabard, J., Corring, T., Ladire, M., Gueugneau, A. M. & Raibaud, P. ( 1993; ). Trypsin-dependent production of an antibacterial substance by a human Peptostreptococcus strain in gnotobiotic rats and in vitro. Appl Environ Microbiol 59, 2876–2883.
    [Google Scholar]
  28. Rod, T. O. & Midtvedt, T. ( 1977; ). Origin of intestinal beta-glucuronidase in germfree, monocontaminated and conventional rats. Acta Pathol Microbiol Scand 85, 271–276.
    [Google Scholar]
  29. Russel, W. M. & Klaenhammer, T. R. ( 2001; ). Identification and cloning of gusA, encoding a new beta-glucuronidase from Lactobacillus gasseri ADH. Appl Environ Microbiol 67, 1253–1261.[CrossRef]
    [Google Scholar]
  30. Schmelz, E. M., Bushnev, A. S., Dillehay, D. L., Sullards, M. C., Liotta, D. C. & Merrill, A. H. ( 1999; ). Ceramide-beta-d-glucuronide: synthesis, digestion, and suppression of early markers of colon carcinogenesis. Cancer Res 59, 5768–5772.
    [Google Scholar]
  31. Shimizu, T., Ohtani, K. Hirakawa, H. & 7 other authors ( 2002; ). Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. Proc Natl Acad Sci U S A 99, 996–1001.[CrossRef]
    [Google Scholar]
  32. Stülke, J. & Hillen, W. ( 1999; ). Carbon catabolite repression in bacteria. Curr Opin Microbiol 2, 195–201.[CrossRef]
    [Google Scholar]
  33. Suau, A., Bonnet, R., Sutren, M., Godon, J. J., Gibson, G. R., Collins, M. D. & Dore, J. ( 1999; ). Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut. Appl Environ Microbiol 65, 4799–4807.
    [Google Scholar]
  34. Tephly, T. R. & Burchell, B. ( 1990; ). UDP-glucuronosyltransferase: a family of detoxifying enzymes. Trends Pharmacol Sci 11, 276–279.[CrossRef]
    [Google Scholar]
  35. Wilson, K. J., Hughes, S. G. & Jefferson, R. A. ( 1992; ). The Escherichia coli gus operon: induction and expression of the gus operon in E. coli and the occurence and use of GUS in other bacteria. In GUS Protocols: Using the GUS Gene as a Reporter of Gene Expression, pp. 7–22. Edited by S. R. Gallagher. San Diego: Academic Press.
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