skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Complex pectin metabolism by gut bacteria reveals novel catalytic functions

Abstract

The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here in this paper we show that the gut bacterium Bacteroides thetaiotaomicron uses the most structurally complex glycan known: the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but 1 of its 21 distinct glycosidic linkages. The deconstruction of rhamnogalacturonan-II side chains and backbone are coordinated to overcome steric constraints, and the degradation involves previously undiscovered enzyme families and catalytic activities. The degradation system informs revision of the current structural model of rhamnogalacturonan-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycan in the human diet.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [4];  [5];  [4];  [6];  [6];  [6];  [6];  [7] more »;  [8];  [3];  [5];  [9];  [1] « less
  1. Newcastle Univ., Newcastle upon Tyne (United Kingdom). Inst. for Cell and Molecular Biosciences
  2. Centre National de la Recherche Scientifique (CNRS), Marseille (France). Architecture et Fonction des Macromolécules Biologiques; Aix-Marseille Univ., Marseille (France)
  3. INRA, Nantes (France). Biopolymères Interactions Assemblages
  4. John Innes Centre Norwich Research Park, Norwich (United Kingdom). Dept. of Biological Chemistry
  5. Univ. of Michigan, Ann Arbor, MI (United States). Medical School, Dept. of Microbiology and Immunology
  6. Univ. of Georgia, Athens, GA (United States). Complex Carbohydrate Research Center
  7. Univ. of York (United Kingdom). Dept. of Chemistry
  8. Lethbridge Research Centre, Lethbridge, AB (Canada)
  9. Centre National de la Recherche Scientifique (CNRS), Marseille (France). Architecture et Fonction des Macromolécules Biologiques; Aix-Marseille Univ., Marseille (France); INRA, Marseille (France); King Abdulaziz Univ., Jeddah (Saudi Arabia). Dept. of Biological Sciences
Publication Date:
Research Org.:
Univ. of Georgia, Athens, GA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1473846
Grant/Contract Number:  
FG02-12ER16324; SC0008472
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Volume: 544; Journal Issue: 7648; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Ndeh, Didier, Rogowski, Artur, Cartmell, Alan, Luis, Ana S., Baslé, Arnaud, Gray, Joseph, Venditto, Immacolata, Briggs, Jonathon, Zhang, Xiaoyang, Labourel, Aurore, Terrapon, Nicolas, Buffetto, Fanny, Nepogodiev, Sergey, Xiao, Yao, Field, Robert A., Zhu, Yanping, O’Neill, Malcolm A., Urbanowicz, Breeanna R., York, William S., Davies, Gideon J., Abbott, D. Wade, Ralet, Marie-Christine, Martens, Eric C., Henrissat, Bernard, and Gilbert, Harry J. Complex pectin metabolism by gut bacteria reveals novel catalytic functions. United States: N. p., 2017. Web. doi:10.1038/nature21725.
Ndeh, Didier, Rogowski, Artur, Cartmell, Alan, Luis, Ana S., Baslé, Arnaud, Gray, Joseph, Venditto, Immacolata, Briggs, Jonathon, Zhang, Xiaoyang, Labourel, Aurore, Terrapon, Nicolas, Buffetto, Fanny, Nepogodiev, Sergey, Xiao, Yao, Field, Robert A., Zhu, Yanping, O’Neill, Malcolm A., Urbanowicz, Breeanna R., York, William S., Davies, Gideon J., Abbott, D. Wade, Ralet, Marie-Christine, Martens, Eric C., Henrissat, Bernard, & Gilbert, Harry J. Complex pectin metabolism by gut bacteria reveals novel catalytic functions. United States. doi:10.1038/nature21725.
Ndeh, Didier, Rogowski, Artur, Cartmell, Alan, Luis, Ana S., Baslé, Arnaud, Gray, Joseph, Venditto, Immacolata, Briggs, Jonathon, Zhang, Xiaoyang, Labourel, Aurore, Terrapon, Nicolas, Buffetto, Fanny, Nepogodiev, Sergey, Xiao, Yao, Field, Robert A., Zhu, Yanping, O’Neill, Malcolm A., Urbanowicz, Breeanna R., York, William S., Davies, Gideon J., Abbott, D. Wade, Ralet, Marie-Christine, Martens, Eric C., Henrissat, Bernard, and Gilbert, Harry J. Thu . "Complex pectin metabolism by gut bacteria reveals novel catalytic functions". United States. doi:10.1038/nature21725. https://www.osti.gov/servlets/purl/1473846.
@article{osti_1473846,
title = {Complex pectin metabolism by gut bacteria reveals novel catalytic functions},
author = {Ndeh, Didier and Rogowski, Artur and Cartmell, Alan and Luis, Ana S. and Baslé, Arnaud and Gray, Joseph and Venditto, Immacolata and Briggs, Jonathon and Zhang, Xiaoyang and Labourel, Aurore and Terrapon, Nicolas and Buffetto, Fanny and Nepogodiev, Sergey and Xiao, Yao and Field, Robert A. and Zhu, Yanping and O’Neill, Malcolm A. and Urbanowicz, Breeanna R. and York, William S. and Davies, Gideon J. and Abbott, D. Wade and Ralet, Marie-Christine and Martens, Eric C. and Henrissat, Bernard and Gilbert, Harry J.},
abstractNote = {The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here in this paper we show that the gut bacterium Bacteroides thetaiotaomicron uses the most structurally complex glycan known: the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but 1 of its 21 distinct glycosidic linkages. The deconstruction of rhamnogalacturonan-II side chains and backbone are coordinated to overcome steric constraints, and the degradation involves previously undiscovered enzyme families and catalytic activities. The degradation system informs revision of the current structural model of rhamnogalacturonan-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycan in the human diet.},
doi = {10.1038/nature21725},
journal = {Nature (London)},
issn = {0028-0836},
number = 7648,
volume = 544,
place = {United States},
year = {2017},
month = {4}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 105 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Structural Basis of the Catalytic Reaction Mechanism of Novel 1,2-α-L-Fucosidase from Bifidobacterium bifidum
journal, April 2007

  • Nagae, Masamichi; Tsuchiya, Atsuko; Katayama, Takane
  • Journal of Biological Chemistry, Vol. 282, Issue 25
  • DOI: 10.1074/jbc.M702246200

The Structure and Function of an Arabinan-specific α-1,2-Arabinofuranosidase Identified from Screening the Activities of Bacterial GH43 Glycoside Hydrolases
journal, February 2011

  • Cartmell, Alan; McKee, Lauren S.; Peña, Maria J.
  • Journal of Biological Chemistry, Vol. 286, Issue 17
  • DOI: 10.1074/jbc.M110.215962

Diffraction-geometry refinement in the DIALS framework
journal, March 2016

  • Waterman, David G.; Winter, Graeme; Gildea, Richard J.
  • Acta Crystallographica Section D Structural Biology, Vol. 72, Issue 4
  • DOI: 10.1107/S2059798316002187

HKL2MAP : a graphical user interface for macromolecular phasing with SHELX programs
journal, September 2004


Structural Insights into the Catalytic Mechanism of Trypanosoma cruzi trans-Sialidase
journal, May 2004


Primary structure of the 2-O-methyl-α-l-fucose-containing side chain of the pectic polysaccharide, rhamnogalacturonan II
journal, February 2003


Synthesis of apiose-containing oligosaccharide fragments of the plant cell wall: fragments of rhamnogalacturonan-II side chains A and B, and apiogalacturonan
journal, January 2011

  • Nepogodiev, Sergey A.; Fais, Margherita; Hughes, David L.
  • Organic & Biomolecular Chemistry, Vol. 9, Issue 19
  • DOI: 10.1039/c1ob05587a

Structural characterization of red wine rhamnogalacturonan II
journal, September 1996


Tetrazoles of manno- and rhamno-pyranoses: Contrasting inhibition of mannosidases by [4.3.0] but of rhamnosidase by [3.3.0] bicyclic tetrazoles
journal, April 1999


Advancing glycomics: Implementation strategies at the Consortium for Functional Glycomics
journal, February 2006

  • Raman, Rahul; Venkataraman, Maha; Ramakrishnan, Subu
  • Glycobiology, Vol. 16, Issue 5
  • DOI: 10.1093/glycob/cwj080

Fitting molecular fragments into electron density
journal, December 2007


Synthesis of a 2,3,4-Triglycosylated Rhamnoside Fragment of Rhamnogalacturonan-II Side Chain A Using a Late Stage Oxidation Approach
journal, February 2005

  • Chauvin, Anne-Laure; Nepogodiev, Sergey A.; Field, Robert A.
  • The Journal of Organic Chemistry, Vol. 70, Issue 3
  • DOI: 10.1021/jo0482864

xia2 : an expert system for macromolecular crystallography data reduction
journal, December 2009


Automatic prediction of polysaccharide utilization loci in Bacteroidetes species
journal, October 2014


MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/S0907444909042073

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

The carbohydrate-active enzymes database (CAZy) in 2013
journal, November 2013

  • Lombard, Vincent; Golaconda Ramulu, Hemalatha; Drula, Elodie
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1178

Identification of 3-deoxy- lyxo -2-heptulosaric acid in the core region of lipopolysaccharides from Rhizobiaceae
journal, December 1991


Starch Catabolism by a Prominent Human Gut Symbiont Is Directed by the Recognition of Amylose Helices
journal, July 2008


Molecular Cloning and Characterization of a β-l-Arabinobiosidase in Bifidobacterium longum That Belongs to a Novel Glycoside Hydrolase Family
journal, December 2010

  • Fujita, Kiyotaka; Sakamoto, Shiho; Ono, Yuki
  • Journal of Biological Chemistry, Vol. 286, Issue 7
  • DOI: 10.1074/jbc.M110.190512

REFMAC 5 dictionary: organization of prior chemical knowledge and guidelines for its use
journal, November 2004

  • Vagin, Alexei A.; Steiner, Roberto A.; Lebedev, Andrey A.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12
  • DOI: 10.1107/S0907444904023510

Isotopic evidence for dietary ecology of late Neandertals in North-Western Europe
journal, August 2016


Crystal Structure of Thermotoga maritima α-l-Fucosidase : INSIGHTS INTO THE CATALYTIC MECHANISM AND THE MOLECULAR BASIS FOR FUCOSIDOSIS
journal, January 2004

  • Sulzenbacher, Gerlind; Bignon, Christophe; Nishimura, Takeshi
  • Journal of Biological Chemistry, Vol. 279, Issue 13
  • DOI: 10.1074/jbc.M313783200

Glycan complexity dictates microbial resource allocation in the large intestine
journal, June 2015

  • Rogowski, Artur; Briggs, Jonathon A.; Mortimer, Jennifer C.
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms8481

A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes
journal, January 2014

  • Larsbrink, Johan; Rogers, Theresa E.; Hemsworth, Glyn R.
  • Nature, Vol. 506, Issue 7489
  • DOI: 10.1038/nature12907

Dissecting conformational contributions to glycosidase catalysis and inhibition
journal, October 2014

  • Speciale, Gaetano; Thompson, Andrew J.; Davies, Gideon J.
  • Current Opinion in Structural Biology, Vol. 28
  • DOI: 10.1016/j.sbi.2014.06.003

How good are my data and what is the resolution?
journal, June 2013

  • Evans, Philip R.; Murshudov, Garib N.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
  • DOI: 10.1107/S0907444913000061

Isolation and characterization of 3-C-carboxy-5-deoxy-l-xylose, a naturally occurring, branched-chain, acidic monosaccharide
journal, October 1983


Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts
journal, December 2011


Rapid similarity search of proteins using alignments of domain arrangements
journal, July 2013


Synthesis of an apiose-containing disaccharide fragment of rhamnogalacturonan-II and some analogues
journal, January 2004


Structural basis for nutrient acquisition by dominant members of the human gut microbiota
journal, January 2017

  • Glenwright, Amy J.; Pothula, Karunakar R.; Bhamidimarri, Satya P.
  • Nature, Vol. 541, Issue 7637
  • DOI: 10.1038/nature20828

Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7
journal, June 2008

  • Langer, Gerrit; Cohen, Serge X.; Lamzin, Victor S.
  • Nature Protocols, Vol. 3, Issue 7
  • DOI: 10.1038/nprot.2008.91

Polysaccharide Composition of Monastrell Red Wines from Four Different Spanish Terroirs: Effect of Wine-Making Techniques
journal, February 2013

  • Apolinar-Valiente, Rafael; Williams, Pascale; Romero-Cascales, Inmaculada
  • Journal of Agricultural and Food Chemistry, Vol. 61, Issue 10
  • DOI: 10.1021/jf304987m

Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism
journal, January 2015

  • Cuskin, Fiona; Lowe, Elisabeth C.; Temple, Max J.
  • Nature, Vol. 517, Issue 7533
  • DOI: 10.1038/nature13995

Experimental phasing with SHELXC / D / E : combining chain tracing with density modification
journal, March 2010

  • Sheldrick, George M.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444909038360

MOLREP an Automated Program for Molecular Replacement
journal, December 1997


Subsite Structure of Saccharomycopsis α-Amylase Secreted from Saccharomyces cerevisiae
journal, April 1991


XDS
journal, January 2010

  • Kabsch, Wolfgang
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
  • DOI: 10.1107/S0907444909047337

RHAMNOGALACTURONAN II: Structure and Function of a Borate Cross-Linked Cell Wall Pectic Polysaccharide
journal, June 2004


Recovery and fine structure variability of RGII sub-domains in wine (Vitis vinifera Merlot)
journal, June 2014

  • Buffetto, F.; Ropartz, D.; Zhang, X. J.
  • Annals of Botany, Vol. 114, Issue 6
  • DOI: 10.1093/aob/mcu097

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

How glycan metabolism shapes the human gut microbiota
journal, April 2012

  • Koropatkin, Nicole M.; Cameron, Elizabeth A.; Martens, Eric C.
  • Nature Reviews Microbiology, Vol. 10, Issue 5
  • DOI: 10.1038/nrmicro2746

    Works referencing / citing this record:

    Specificity and mechanism of carbohydrate demethylation by cytochrome P450 monooxygenases
    journal, December 2018

    • Robb, Craig S.; Reisky, Lukas; Bornscheuer, Uwe T.
    • Biochemical Journal, Vol. 475, Issue 23
    • DOI: 10.1042/bcj20180762

    Glycan utilisation system in Bacteroides and Bifidobacteria and their roles in gut stability and health
    journal, July 2019


    Glycan utilisation system in Bacteroides and Bifidobacteria and their roles in gut stability and health
    journal, July 2019


    Identification of endoxylanase XynE from Clostridium thermocellum as the first xylanase of glycoside hydrolase family GH141
    journal, September 2017


    Specificity and mechanism of carbohydrate demethylation by cytochrome P450 monooxygenases
    journal, December 2018

    • Robb, Craig S.; Reisky, Lukas; Bornscheuer, Uwe T.
    • Biochemical Journal, Vol. 475, Issue 23
    • DOI: 10.1042/bcj20180762

    Expanding roles for pectins in plant development
    journal, July 2018

    • Saffer, Adam M.
    • Journal of Integrative Plant Biology, Vol. 60, Issue 10
    • DOI: 10.1111/jipb.12662

    Specificity and mechanism of carbohydrate demethylation by cytochrome P450 monooxygenases
    text, January 2018

    • Robb, Craig S.; Reisky, Lukas; Bornscheuer, Uwe T.
    • Deutsches Elektronen-Synchrotron, DESY, Hamburg
    • DOI: 10.3204/pubdb-2019-00025