Fucosidases from the human gut symbiont Ruminococcus gnavus

Wu, Haiyang, Rebello, Osmond, Crost, Emmanuelle H, Owen, C David, Walpole, Samuel, Bennati-Granier, Chloe, Ndeh, Didier, Monaco, Serena, Hicks, Thomas, Colvile, Anna, Urbanowicz, Paulina A, Walsh, Martin A, Angulo, Jesus, Spencer, Daniel I R and Juge, Nathalie (2020) Fucosidases from the human gut symbiont Ruminococcus gnavus. Cellular and Molecular Life Sciences. ISSN 1420-682X

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Abstract

The availability and repartition of fucosylated glycans within the gastrointestinal tract contributes to the adaptation of gut bacteria species to ecological niches. To access this source of nutrients, gut bacteria encode α-L-fucosidases (fucosidases) which catalyze the hydrolysis of terminal α-L-fucosidic linkages. We determined the substrate and linkage specificities of fucosidases from the human gut symbiont Ruminococcus gnavus. Sequence similarity network identified strain-specific fucosidases in R. gnavus ATCC 29149 and E1 strains that were further validated enzymatically against a range of defined oligosaccharides and glycoconjugates. Using a combination of glycan microarrays, mass spectrometry, isothermal titration calorimetry, crystallographic and saturation transfer difference NMR approaches, we identified a fucosidase with the capacity to recognize sialic acid-terminated fucosylated glycans (sialyl Lewis X/A epitopes) and hydrolyze α1-3/4 fucosyl linkages in these substrates without the need to remove sialic acid. Molecular dynamics simulation and docking showed that 3'-Sialyl Lewis X (sLeX) could be accommodated within the binding site of the enzyme. This specificity may contribute to the adaptation of R. gnavus strains to the infant and adult gut and has potential applications in diagnostic glycomic assays for diabetes and certain cancers.

Item Type: Article
Uncontrolled Keywords: antennary fucose,glycoside hydrolase,gut microbiota,lewis epitopes,mucin glycosylation,mucus,molecular medicine,molecular biology,pharmacology,cellular and molecular neuroscience,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1313
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Pharmacy
Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 01 May 2020 00:06
Last Modified: 28 Jul 2020 00:13
URI: https://ueaeprints.uea.ac.uk/id/eprint/74923
DOI: 10.1007/s00018-020-03514-x

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