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Methionine synthesis and glycine betaine demethylation are intricately intertwined in cosmopolitan marine bacteria

Title: Methionine synthesis and glycine betaine demethylation are intricately intertwined in cosmopolitan marine bacteria
Authors: Mausz, Michaela A.; Murphy, Andrew R. J.; del Mar Aguilo-Ferretjans, Maria; Hitchcock, Andrew; Moran, Mary Ann; Scanlan, David J.; Chen, Yin; Lidbury, Ian D. E. A.
Publisher Information: National Academy of Sciences
Publication Year: 2025
Collection: The University of Warwick: WRAP - Warwick Research Archive Portal
Subject Terms: QD Chemistry; QR Microbiology
Description: 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 Ruegeria pomeroyi 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, mtgC 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 0027-8424
Relation: https://wrap.warwick.ac.uk/id/eprint/193588/1/mausz-et-al-2025-methionine-synthesis-and-glycine-betaine-demethylation-are-intricately-intertwined-in-cosmopolitan.pdf; Mausz, Michaela A., Murphy, Andrew R. J., del Mar Aguilo-Ferretjans, Maria, Hitchcock, Andrew, Moran, Mary Ann, Scanlan, David J., Chen, Yin and Lidbury, Ian D. E. A. (2025) Methionine synthesis and glycine betaine demethylation are intricately intertwined in cosmopolitan marine bacteria. Proceedings of the National Academy of Sciences of the United States of America, 122 (38). e2426167122. doi:10.1073/pnas.2426167122 ISSN 0027-8424.
DOI: 10.1073/pnas.2426167122
Availability: https://wrap.warwick.ac.uk/id/eprint/193588/; https://doi.org/10.1073/pnas.2426167122
Rights: cc_by_4
Accession Number: edsbas.2398446A
Database: BASE