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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:p>\n                    Across all domains of life, cobalamin-dependent methyltransferases have diversified to perform a range of crucial functions, such as methionine synthesis and the demethylation of various reduced nitrogen and sulfur compounds. These large modular enzymes typically possess three substrate-binding domains, two binding either the methyl donor or methyl acceptor, as well as a cobalamin-binding domain. Here, by challenging the current paradigm of glycine betaine (GBT) catabolism, we have identified a unique methyltransferase in aerobic environmental bacteria that has a dual function both as a methionine synthase and a GBT methyltransferase. Using the marine bacterium\n                    <jats:italic toggle=\"yes\">Ruegeria pomeroyi<\/jats:italic>\n                    DSS-3 as a model, we demonstrate that a core cobalamin-binding domain (MtgC) and a bidirectional methyltransferase (MtgD) are essential for both methionine synthesis and GBT demethylation. MtgC is phylogenetically distinct from the cobalamin-binding domains of either the classical methionine synthase (MetH) or the GBT methyltransferases found in anaerobic bacteria and archaea. Across the global ocean,\n                    <jats:italic toggle=\"yes\">mtgC<\/jats:italic>\n                    expression is frequently greater than previously known GBT catabolic pathways due to its occurrence in abundant cosmopolitan marine bacteria. Thus, we uncover a unique relationship between GBT catabolism and methionine synthesis in nature and identify a major route for N-osmolyte demethylation in the global ocean.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2426167122","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T17:55:08Z","timestamp":1758045308000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["Methionine synthesis and glycine betaine demethylation are intricately intertwined in cosmopolitan marine bacteria"],"prefix":"10.1073","volume":"122","author":[{"given":"Michaela A.","family":"Mausz","sequence":"first","affiliation":[{"name":"School of Life Sciences, University of Warwick","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6586-2363","authenticated-orcid":false,"given":"Andrew R. 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