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To meet this demand in a competitive and diverse cobamide environment of the gut,\n                    <jats:italic>B<\/jats:italic>\n                    <jats:italic>.<\/jats:italic>\n                    <jats:italic>thetaiotaomicron<\/jats:italic>\n                    employs a B\n                    <jats:sub>12<\/jats:sub>\n                    \u2010uptake (Btu) system that extends far beyond the well\u2010studied\n                    <jats:italic>Escherichia<\/jats:italic>\n                    <jats:italic>coli<\/jats:italic>\n                    Btu system. Rather than relying on a single outer membrane (OM) transporter,\n                    <jats:italic>B<\/jats:italic>\n                    <jats:italic>.<\/jats:italic>\n                    <jats:italic>thetaiotaomicron<\/jats:italic>\n                    deploys a multiprotein extracellular relay in which surface\u2010exposed BtuJ lipoproteins capture cobamides extracellularly and transfer them to BtuH and BtuG lipoproteins at the OM. BtuG forms a stable complex with the TonB\u2010dependent transporter BtuB, coupling cobamide capture to periplasmic translocation, and the inner membrane BtuFCD complex completes cytoplasmic delivery. BtuJ\u2010enriched OM vesicles further extend cobamide capture into the extracellular environment, and cobamide\u2010dependent riboswitches couple Btu protein expression to the availability and chemical identity of intracellular cobamides. We review the structural and mechanistic evidence for each stage of this relay, propose a model for cobamide import, and identify outstanding questions that will illuminate cobamide scavenging across gut bacteria.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70539","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:36:52Z","timestamp":1790537812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cobamide Scavenging and Import via a Multiprotein Extracellular Relay in\n                    <i>Bacteroides thetaiotaomicron<\/i>"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4585-4370","authenticated-orcid":false,"given":"Alexander","family":"Drake","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry Institute of Molecular Biology University of Oregon  Eugene Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5099-3528","authenticated-orcid":false,"given":"Romila","family":"Mascarenhas","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Institute of Molecular Biology University of Oregon  Eugene Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba0165"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010micro\u2010051024\u2010044734"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.10.002"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2016.06.011"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2259"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00275\u201016"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.1c00083"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr900104z"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.12.007"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41396\u2010018\u20100304\u20109"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2019.08.005"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00148"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102958.1990.tb00562.x"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.106.3.751\u2010757.1971"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.262659699"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080029"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.08.003"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.37138"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201040427\u20102"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20253340"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161828"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.01407\u201024"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969\u20102126(96)00037\u20108"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7992050"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01303\u201019"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2020.06.014"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/195340a0"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u2010291X(60)90252\u20107"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u2010291X(64)90363\u20108"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)97442\u20109"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2010.05.025"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01121\u201022"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/87.5.1324"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.2c00367"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071142"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010micro\u2010032421\u2010111116"},{"key":"e_1_2_16_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127694"},{"key":"e_1_2_16_39_1","doi-asserted-by":"crossref","unstructured":"J.Whittaker J. 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