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However, this approach has been hindered by poor cell growth on methanol, largely due to the methanol toxicity and possible competition of the precursor pyruvate between the tricarboxylic acid cycle and lactate synthesis. To address this, we developed an in vivo multi\u2010enzymatic catalysis system in the methylotrophic yeast\n                    <jats:italic>Ogataea polymorpha<\/jats:italic>\n                    for direct L\u2010lactate production from methanol. We determined that the optimal process involves cell culture and enzyme induction in a mixed glucose and methanol, followed by a dedicated cell catalysis phase. Finally, by integrating CO\n                    <jats:sub>2<\/jats:sub>\n                    hydrogenation with this multi\u2010enzymatic pathway, we achieved an L\u2010lactate titer of 19 g\/L from methanol in a 5 L bioreactor within 46 h, with a yield of 0.30 g\/g and a productivity of 407 mg\/L\/h. This established in vivo catalysis platform demonstrates significant potential for expanding methanol biotransformation into a wider array of valuable chemicals.\n                  <\/jats:p>","DOI":"10.1002\/biot.70211","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:29:51Z","timestamp":1774272591000},"source":"Crossref","is-referenced-by-count":1,"title":["In Vivo Multi\u2010Enzymatic Catalysis for Bioproduction of L\u2010Lactic Acid from Sole Methanol"],"prefix":"10.1002","volume":"21","author":[{"given":"Yunxia","family":"Li","sequence":"first","affiliation":[{"name":"School of Biological Engineering Dalian Polytechnic University  Dalian P. R. China"},{"name":"Division of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian P. R. China"},{"name":"Dalian Key Laboratory of Energy Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian P. R. 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