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We recently discovered that an isoform of FMO, <jats:italic>fmo\u20102<\/jats:italic> in <jats:italic>Caenorhabditis elegans<\/jats:italic>, alters endogenous metabolism to impact longevity and stress tolerance. Increased expression of <jats:italic>fmo\u20102<\/jats:italic> in <jats:italic>C. elegans<\/jats:italic> modifies the flux through the key pathway known as One Carbon Metabolism (OCM). This modified flux results in a decrease in the ratio of S\u2010adenosyl\u2010methionine (SAM) to S\u2010adenosyl\u2010homocysteine (SAH), consequently diminishing methylation capacity. Here we discuss how FMO\u20102\u2010mediated formate production during tryptophan metabolism may serve as a trigger for changing the flux in OCM. We suggest formate bridges tryptophan and OCM, altering metabolic flux away from methylation during <jats:italic>fmo\u20102<\/jats:italic> overexpression. Additionally, we highlight how these metabolic results intersect with the mTOR and AMPK pathways, in addition to mitochondrial metabolism. In conclusion, the goal of this essay is to bring attention to the central role of FMO enzymes but lack of understanding of their mechanisms. We justify a call for a deeper understanding of FMO enzyme's role in metabolic rewiring through tryptophan\/formate or other yet unidentified substrates. Additionally, we emphasize the identification of novel drugs and microbes to induce FMO activity and extend lifespan.<\/jats:p>","DOI":"10.1002\/bies.202400029","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T18:39:21Z","timestamp":1715107161000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Flavin\u2010containing monooxygenase (FMO): Beyond xenobiotics"],"prefix":"10.1002","volume":"46","author":[{"given":"Ajay","family":"Bhat","sequence":"first","affiliation":[{"name":"Molecular &amp; Integrative Physiology Department University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith R.","family":"Carranza","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology Program University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela 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