An Atlas of β-Glucuronidases in the Human Intestinal Microbiome

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2017 Jun 6

PMID 28578872

Citations 115

Authors

Rebecca M Pollet

Emma H DAgostino

William G Walton

Yongmei Xu

Michael S Little

Kristen A Biernat

Samuel J Pellock

Loraine M Patterson

Benjamin C Creekmore

Hanna N Isenberg

Rohini R Bahethi

Aadra P Bhatt

Jian Liu

Raad Z Gharaibeh

Matthew R Redinbo

Affiliations

Soon will be listed here.

Abstract

Microbiome-encoded β-glucuronidase (GUS) enzymes play important roles in human health by metabolizing drugs in the gastrointestinal (GI) tract. The numbers, types, and diversity of these proteins in the human GI microbiome, however, remain undefined. We present an atlas of GUS enzymes comprehensive for the Human Microbiome Project GI database. We identify 3,013 total and 279 unique microbiome-encoded GUS proteins clustered into six unique structural categories. We assign their taxonomy, assess cellular localization, reveal the inter-individual variability within the 139 individuals sampled, and discover 112 novel microbial GUS enzymes. A representative in vitro panel of the most common GUS proteins by read abundances highlights structural and functional variabilities within the family, including their differential processing of smaller glucuronides and larger carbohydrates. These data provide a sequencing-to-molecular roadmap for examining microbiome-encoded enzymes essential to human health.

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References

McBain A, Macfarlane G . 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. 1999; 47(5):407-16. DOI: 10.1099/00222615-47-5-407. View

Roberts A, Wallace B, Venkatesh M, Mani S, Redinbo M . Molecular insights into microbial β-glucuronidase inhibition to abrogate CPT-11 toxicity. Mol Pharmacol. 2013; 84(2):208-17. PMC: 3716326. DOI: 10.1124/mol.113.085852. View

. A framework for human microbiome research. Nature. 2012; 486(7402):215-21. PMC: 3377744. DOI: 10.1038/nature11209. View

LoGuidice A, Wallace B, Bendel L, Redinbo M, Boelsterli U . Pharmacologic targeting of bacterial β-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice. J Pharmacol Exp Ther. 2012; 341(2):447-54. PMC: 3336811. DOI: 10.1124/jpet.111.191122. View

Boelsterli U, Redinbo M, Saitta K . Multiple NSAID-induced hits injure the small intestine: underlying mechanisms and novel strategies. Toxicol Sci. 2012; 131(2):654-67. PMC: 3551426. DOI: 10.1093/toxsci/kfs310. View

Wallace B, Wang H, Lane K, Scott J, Orans J, Koo J . Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010; 330(6005):831-5. PMC: 3110694. DOI: 10.1126/science.1191175. View

Huson D, Scornavacca C . Dendroscope 3: an interactive tool for rooted phylogenetic trees and networks. Syst Biol. 2012; 61(6):1061-7. DOI: 10.1093/sysbio/sys062. View

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T . SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. 2014; 42(Web Server issue):W252-8. PMC: 4086089. DOI: 10.1093/nar/gku340. View

10.

Finn R, Coggill P, Eberhardt R, Eddy S, Mistry J, Mitchell A . The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res. 2015; 44(D1):D279-85. PMC: 4702930. DOI: 10.1093/nar/gkv1344. View

11.

Mackenzie P, Owens I, Burchell B, Bock K, Bairoch A, Belanger A . The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics. 1997; 7(4):255-69. DOI: 10.1097/00008571-199708000-00001. View

12.

Redinbo M . The microbiota, chemical symbiosis, and human disease. J Mol Biol. 2014; 426(23):3877-91. PMC: 4252811. DOI: 10.1016/j.jmb.2014.09.011. View

13.

Juncker A, Willenbrock H, von Heijne G, Brunak S, Nielsen H, Krogh A . Prediction of lipoprotein signal peptides in Gram-negative bacteria. Protein Sci. 2003; 12(8):1652-62. PMC: 2323952. DOI: 10.1110/ps.0303703. View

14.

. Structure, function and diversity of the healthy human microbiome. Nature. 2012; 486(7402):207-14. PMC: 3564958. DOI: 10.1038/nature11234. View

15.

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

16.

Kelley L, Mezulis S, Yates C, Wass M, Sternberg M . The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015; 10(6):845-58. PMC: 5298202. DOI: 10.1038/nprot.2015.053. View

17.

Matsumura I, Ellington A . In vitro evolution of beta-glucuronidase into a beta-galactosidase proceeds through non-specific intermediates. J Mol Biol. 2000; 305(2):331-9. DOI: 10.1006/jmbi.2000.4259. View

18.

Sievers F, Wilm A, Dineen D, Gibson T, Karplus K, Li W . Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011; 7:539. PMC: 3261699. DOI: 10.1038/msb.2011.75. View

19.

Koropatkin N, Cameron E, Martens E . How glycan metabolism shapes the human gut microbiota. Nat Rev Microbiol. 2012; 10(5):323-35. PMC: 4005082. DOI: 10.1038/nrmicro2746. View

20.

Meech R, Miners J, Lewis B, Mackenzie P . The glycosidation of xenobiotics and endogenous compounds: versatility and redundancy in the UDP glycosyltransferase superfamily. Pharmacol Ther. 2012; 134(2):200-18. DOI: 10.1016/j.pharmthera.2012.01.009. View