{"doi":"10.1038/s41467-024-48802-3","title":"Human gut microbes express functionally distinct endoglycosidases to metabolize the same N-glycan substrate","abstract":"Bacteroidales (syn. Bacteroidetes) are prominent members of the human gastrointestinal ecosystem mainly due to their efficient glycan-degrading machinery, organized into gene clusters known as polysaccharide utilization loci (PULs). A single PUL was reported for catabolism of high-mannose (HM) N-glycan glyco-polypeptides in the gut symbiont Bacteroides thetaiotaomicron, encoding a surface endo-β-N-acetylglucosaminidase (ENGase), BT3987. Here, we discover an ENGase from the GH18 family in B. thetaiotaomicron, BT1285, encoded in a distinct PUL with its own repertoire of proteins for catabolism of the same HM N-glycan substrate as that of BT3987. We employ X-ray crystallography, electron microscopy, mass spectrometry-based activity measurements, alanine scanning mutagenesis and a broad range of biophysical methods to comprehensively define the molecular mechanism by which BT1285 recognizes and hydrolyzes HM N-glycans, revealing that the stabilities and activities of BT1285 and BT3987 were optimal in markedly different conditions. BT1285 exhibits significantly higher affinity and faster hydrolysis of poorly accessible HM N-glycans than does BT3987. We also find that two HM-processing endoglycosidases from the human gut-resident Alistipes finegoldii display condition-specific functional properties. Altogether, our data suggest that human gut microbes employ evolutionary strategies to express distinct ENGases in order to optimally metabolize the same N-glycan substrate in the gastroinstestinal tract.","journal":"Nature Communications","year":2024,"id":424663,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":506068,"name":"Nazneen Sultana","orcid":"0000-0001-9866-4443","position":1,"is_corresponding":false},{"id":1221608,"name":"M.V.A.S. Navarro","orcid":"0000-0002-2461-0431","position":2,"is_corresponding":false},{"id":1167086,"name":"Maroš Huličiak","orcid":"0000-0002-9929-3522","position":3,"is_corresponding":false},{"id":456328,"name":"Jonathan J. Du","orcid":"0000-0002-7750-4413","position":4,"is_corresponding":false},{"id":456329,"name":"Javier O. Cifuente","orcid":"0000-0001-5420-121X","position":5,"is_corresponding":false},{"id":618083,"name":"Maria W. Flowers","orcid":"0000-0002-1814-7049","position":6,"is_corresponding":false},{"id":366621,"name":"Xu Liu","orcid":"0000-0003-2252-7148","position":7,"is_corresponding":false},{"id":409323,"name":"Pete Lollar","orcid":"0000-0002-1206-8104","position":8,"is_corresponding":false},{"id":278987,"name":"Beatriz Trastoy","orcid":"0000-0002-2178-732X","position":9,"is_corresponding":false},{"id":278991,"name":"Marcelo E. Guerin","orcid":"0000-0001-9524-3184","position":10,"is_corresponding":false},{"id":356052,"name":"Eric J. Sundberg","orcid":"0000-0003-0478-3033","position":11,"is_corresponding":false},{"id":995801,"name":"Diego E. Sastre","orcid":"0000-0003-2010-5398","position":0,"is_corresponding":true}],"reference_count":103,"raw_metadata":null,"created_at":"2026-07-19T01:58:21.523756Z","pmid":"38879612","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}