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While the biosynthesis of mycofactocin is well established, the gene\n                    <jats:italic>mftG<\/jats:italic>\n                    , which encodes an oxidoreductase of the glucose-methanol-choline superfamily, remained functionally uncharacterized. Here, we show that MftG enzymes are almost exclusively found in genomes containing mycofactocin biosynthetic genes and are present in 75% of organisms harboring these genes. Gene deletion experiments in\n                    <jats:italic>Mycolicibacterium smegmatis<\/jats:italic>\n                    demonstrated a growth defect of the \u2206\n                    <jats:italic>mftG<\/jats:italic>\n                    mutant on ethanol as a carbon source, accompanied by an arrest of cell division reminiscent of mild starvation. Investigation of carbon and cofactor metabolism implied a defect in mycofactocin reoxidation. Cell-free enzyme assays and respirometry using isolated cell membranes indicated that MftG acts as a mycofactocin dehydrogenase shuttling electrons toward the respiratory chain. Transcriptomics studies also indicated remodeling of redox metabolism to compensate for a shortage of redox equivalents. In conclusion, this work closes an important knowledge gap concerning the mycofactocin system and adds a new pathway to the intricate web of redox reactions governing the metabolism of mycobacteria.\n                  <\/jats:p>","DOI":"10.7554\/elife.97559","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T14:25:09Z","timestamp":1718375109000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.97559","source":"Crossref","is-referenced-by-count":1,"title":["MftG is crucial for ethanol metabolism of mycobacteria by linking mycofactocin oxidation to respiration"],"prefix":"10.7554","volume":"13","author":[{"given":"Ana Patr\u00edcia","family":"Grac\u0327a","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055s37c97","id-type":"ROR","asserted-by":"publisher"}],"name":"Leibniz Institute for Natural Product Research and Infection Biology \u2013 Hans Kn\u00f6ll Institute, Junior Research Group Synthetic Microbiology","place":["Jena, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Vadim","family":"Nikitushkin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055s37c97","id-type":"ROR","asserted-by":"publisher"}],"name":"Leibniz Institute for Natural Product Research and Infection Biology \u2013 Hans Kn\u00f6ll Institute, Junior Research Group Synthetic Microbiology","place":["Jena, Germany"]},{"id":[{"id":"https:\/\/ror.org\/0234wmv40","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Bayreuth, Chair of Biochemistry of Microorganisms","place":["Kulmbach, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Mark","family":"Ellerhorst","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055s37c97","id-type":"ROR","asserted-by":"publisher"}],"name":"Leibniz Institute for Natural Product Research and Infection Biology \u2013 Hans Kn\u00f6ll Institute, Junior Research Group Synthetic Microbiology","place":["Jena, Germany"]},{"id":[{"id":"https:\/\/ror.org\/0234wmv40","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Bayreuth, Chair of Biochemistry of Microorganisms","place":["Kulmbach, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Cl\u00e1udia","family":"Vilhena","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055s37c97","id-type":"ROR","asserted-by":"publisher"}],"name":"Leibniz Institute for Natural Product Research and Infection Biology\u2013 Hans Kn\u00f6ll Institute, Department of Infection Biology","place":["Jena, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Tilman E","family":"Klassert","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03d0p2685","id-type":"ROR","asserted-by":"publisher"}],"name":"Respiratory Infection Dynamics, Helmholtz Centre for Infection Research - 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