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The model acetogen <jats:italic>Acetobacterium woodii<\/jats:italic> can grow on CO<jats:sub>2<\/jats:sub>, formate or methanol, but not on carbon monoxide, an important industrial waste product. Since hydrogenases are targets of CO inhibition, here, we genetically delete the two [FeFe] hydrogenases HydA2 and HydBA in <jats:italic>A. woodii<\/jats:italic>. We show that the \u2206<jats:italic>hydBA\/hydA2<\/jats:italic> mutant indeed grows on CO and produces acetate, but only after a long adaptation period. SNP analyzes of CO-adapted cells reveal a mutation in the HycB2 subunit of the HydA2\/HydB2\/HydB3\/Fdh-containing hydrogen-dependent CO<jats:sub>2<\/jats:sub> reductase (HDCR). We observe an increase in ferredoxin-dependent CO<jats:sub>2<\/jats:sub> reduction and vice versa by the HDCR in the absence of the HydA2 module and speculate that this is caused by the mutation in HycB2. In addition, the CO-adapted \u2206<jats:italic>hydBA\/hydA2<\/jats:italic> mutant growing on formate has a final biomass twice of that of the wild type.<\/jats:p>","DOI":"10.1038\/s41467-024-49680-5","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T18:08:08Z","timestamp":1719425288000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Redirecting electron flow in Acetobacterium woodii enables growth on CO and improves growth on formate"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3806-3520","authenticated-orcid":false,"given":"Jimyung","family":"Moon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-6202","authenticated-orcid":false,"given":"Anja","family":"Poehlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8646-7925","authenticated-orcid":false,"given":"Rolf","family":"Daniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7955-5508","authenticated-orcid":false,"given":"Volker","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"49680_CR1","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1146\/annurev.mi.37.100183.001425","volume":"37","author":"O Meyer","year":"1983","unstructured":"Meyer, O. & Schlegel, H. 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