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Although efforts have been made to engineer microbial hosts such as <jats:italic>Corynebacterium glutamicum<\/jats:italic> to produce 1,2-PDO from renewable resources, the performance of such strains is still improvable to be competitive with existing petrochemical production routes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this study, we enabled 1,2-PDO production in the genome-reduced strain <jats:italic>C. glutamicum<\/jats:italic> PC2 by introducing previously described modifications. The resulting strain showed reduced product formation but secreted 50\u2009\u00b1\u20091 mM <jats:sc>d<\/jats:sc>-lactate as byproduct. <jats:italic>C. glutamicum<\/jats:italic> PC2 lacks the <jats:sc>d<\/jats:sc>-lactate dehydrogenase which pointed to a yet unknown pathway relevant for 1,2-PDO production. Further analysis indicated that in <jats:italic>C. glutamicum<\/jats:italic> methylglyoxal, the precursor for 1,2-PDO synthesis, is detoxified with the antioxidant native mycothiol (MSH) by a glyoxalase-like system to lactoylmycothiol and converted to <jats:sc>d<\/jats:sc>-lactate which is rerouted into the central carbon metabolism at the level of pyruvate. Metabolomics of cell extracts of the empty vector-carrying wildtype, a 1,2-PDO producer and its derivative with inactive <jats:sc>d<\/jats:sc>-lactate dehydrogenase identified major mass peaks characteristic for lactoylmycothiol and its precursors MSH and glucosaminyl-myo-inositol, whereas the respective mass peaks were absent in a production strain with inactivated MSH synthesis. Deletion of <jats:italic>mshA<\/jats:italic>, encoding MSH synthase, in the 1,2-PDO producing strain <jats:italic>C. glutamicum<\/jats:italic> \u0394<jats:italic>hdpA<\/jats:italic>\u0394<jats:italic>ldh<\/jats:italic>(pEKEx3-<jats:italic>mgsA<\/jats:italic>-<jats:italic>yqhD<\/jats:italic>-<jats:italic>gldA<\/jats:italic>) improved the product yield by 56% to 0.53\u2009\u00b1\u20090.01 mM<jats:sub>1,2\u2212PDO<\/jats:sub> mM<jats:sub>glucose<\/jats:sub><jats:sup>\u22121<\/jats:sup> which is the highest value for <jats:italic>C. glutamicum<\/jats:italic> reported so far.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Genome reduced-strains are a useful basis to unravel metabolic constraints for strain engineering and disclosed in this study the pathway to detoxify methylglyoxal which represents a precursor for 1,2-PDO production. Subsequent inactivation of the competing pathway significantly improved the 1,2-PDO yield.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12934-024-02337-w","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T05:02:34Z","timestamp":1708750954000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A genome-reduced Corynebacterium glutamicum derivative discloses a hidden pathway relevant for 1,2-propanediol production"],"prefix":"10.1186","volume":"23","author":[{"given":"Daniel","family":"Siebert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Glawischnig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Theres","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke","family":"Vannahme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Salazar-Quir\u00f3s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Weiske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezgi","family":"Saydam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"M\u00f6ggenried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker F.","family":"Wendisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Blombach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,24]]},"reference":[{"key":"2337_CR1","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1002\/biot.201000140","volume":"5","author":"H Liu","year":"2010","unstructured":"Liu H, Xu Y, Zheng Z, Liu D. 1,3-Propanediol and its copolymers: research, development and industrialization. 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