@article{84ddb148c9774d86982c872487a5f338,
title = "Fucosidases from the human gut symbiont Ruminococcus gnavus",
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.",
keywords = "Antennary fucose, Glycoside hydrolase, Gut microbiota, Lewis epitopes, Mucin glycosylation, Mucus",
author = "Haiyang Wu and Osmond Rebello and Crost, {Emmanuelle H.} and Owen, {C. David} and Samuel Walpole and Chloe Bennati-Granier and Didier Ndeh and Serena Monaco and Thomas Hicks and Anna Colvile and Urbanowicz, {Paulina A.} and Walsh, {Martin A.} and Jesus Angulo and Spencer, {Daniel I. R.} and Nathalie Juge",
note = "Funding Information: The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); this research was mostly funded by the Innovate UK Biocatalyst grant Glycoenzymes for Bioindustries (BB/M029042/) with contribution from the Royal Society and the BBSRC Institute Strategic Programmes BB/J004529/1 {\textquoteleft}The Gut Health and Food Safety{\textquoteright} and BB/R012490/1 {\textquoteleft}Gut Microbes and Health{\textquoteright} and its consituent project BBS/E/F/000PR10353 (Theme 1, Determinants of microbe-host responses in the gut across life). We would like to thank Diamond Light Source beamlines VMXi, I03 and I04 for beamtime and assistance, as well as the crystallization facility at Harwell for access and support. We wish to acknowledge the Consortium for Functional Glycomics grant number GM62116 and GM098791 for glycan screening. Osmond Rebello received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie grant agreement GlySign No 722095. Serena Monaco and Jes{\'u}s Angulo acknowledge financial support from BBSRC (BB/P010660/1). Jes{\'u}s Angulo also acknowledges financial support from the Universidad de Sevilla (Acciones Especiales del VI Plan Propio de Investigaci{\'o}n y transferencia). Samuel Walpole and Thomas Hicks acknowledge BBSRC DTP studentships. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = apr,
day = "24",
doi = "10.1007/s00018-020-03514-x",
language = "English",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Springer Verlag",
}
