@article{a62a8329b5514e43a8d142f98642fdcc,
title = "Complex N-glycan breakdown by gut Bacteroides involves an extensive enzymatic apparatus encoded by multiple co-regulated genetic loci",
abstract = "Glycans are the major carbon sources available to the human colonic microbiota. Numerous N-glycosylated proteins are found in the human gut, from both dietary and host sources, including immunoglobulins such as IgA that are secreted into the intestine at high levels. Here, we show that many mutualistic gut Bacteroides spp. have the capacity to utilize complex N-glycans (CNGs) as nutrients, including those from immunoglobulins. Detailed mechanistic studies using transcriptomic, biochemical, structural and genetic techniques reveal the pathway employed by Bacteroides thetaiotaomicron (Bt) for CNG degradation. The breakdown process involves an extensive enzymatic apparatus encoded by multiple non-adjacent loci and comprises 19 different carbohydrate-active enzymes from different families, including a CNG-specific endo-glycosidase activity. Furthermore, CNG degradation involves the activity of carbohydrate-active enzymes that have previously been implicated in the degradation of other classes of glycan. This complex and diverse apparatus provides Bt with the capacity to access the myriad different structural variants of CNGs likely to be found in the intestinal niche.",
keywords = "Bacterial genetics, Biochemistry, Microbiome, Structural biology",
author = "Justina Briliūtė and Urbanowicz, {Paulina A.} and Luis, {Ana S.} and Arnaud Basl{\'e} and Neil Paterson and Osmond Rebello and Jenifer Hendel and Ndeh, {Didier A.} and Lowe, {Elisabeth C.} and Martens, {Eric C.} and Spencer, {Daniel I. R.} and Bolam, {David N.} and Crouch, {Lucy I.}",
note = "Funding Information: We thank C. Morland (Newcastle University, UK) for his expert technical assistance, and F. Cuskin (Newcastle University, UK) and L. Royle (Ludger, UK) for insightful conversations about the data. We would like to thank Diamond Light Source (Oxfordshire, UK) for beamtime (proposal mx13587 and mx18598) and the staff of beamline I03 and 104-1 for assistance with crystal testing and data collection. We thank J. Casement (Bioinformatics Support Unit, Newcastle University, UK) for analysing the raw RNA-Seq data. We thank J. Sonnenberg (Stanford, USA) for the ΔBT0455 Bt strain, R. Lewis (Newcastle University, UK) for his guidance and advice in looking for structural homologues and R. Hirt (Newcastle University, UK) for his advice on phylogenetics. The work was funded by the BBSRC/Innovate UK IB catalyst award to D.N.B. {\textquoteleft}Glycoenzymes for Bioindustries{\textquoteright} (BB/M029018/1). Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2019",
month = sep,
doi = "10.1038/s41564-019-0466-x",
language = "English",
volume = "4",
pages = "1571--1581",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Publishing Group",
number = "9",
}