{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:19:58Z","timestamp":1783088398905,"version":"3.54.6"},"reference-count":43,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":123,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Industrial production of malic acid remains dependent on fossil resources or, when performed microbiologically, on sugar-based feedstocks. Both routes come with caveats, generating emissions and competing with food supply. The use of CO\u2082-derived one-carbon substrates offers a promising alternative to circumvent these constraints. In this study, the malic acid production process from methanol in metabolically engineered Ogataea polymorpha NYCY495 LEU-\u0394STE12 Pyc Mdh MAE1 strain was optimized and scaled up. A two-phase cultivation strategy, using glycerol for biomass formation and methanol for product synthesis, was established in shake flasks and subsequently transferred to a 1\u00a0L bioreactor. Process optimization through automated feeding strategies was evaluated. DO-based feeding was the most effective approach, using a combination of methanol and glycerol, achieving a final molar yield of 0.1 molMA molMeOH \u207b\u00b9 and a maximum productivity of 0.5\u00a0g l\u207b\u00b9 h\u207b\u00b9. This successful fermentation strategy was validated using green methanol, showcasing the feasibility of \u201cclosing the loop\u201d as envisioned in the bioeconomy. Finally, a comparative study of the effect of glycerol, methanol, and their mixture on O. polymorpha NYCY495 LEU-\u0394STE12 Pyc Mdh MAE1 methanol metabolism, peroxisome biogenesis, and cellular redox balance is presented, supporting the positive cumulative effect of both on gene transcription.<\/jats:p>","DOI":"10.1093\/femsyr\/foag017","type":"journal-article","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T21:08:45Z","timestamp":1777842525000},"source":"Crossref","is-referenced-by-count":0,"title":["Optimization and scale up of L-malic acid production from methanol by the methylotrophic yeast\n                    <i>Ogataea polymorpha<\/i>"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8669-0127","authenticated-orcid":false,"given":"Alessandra","family":"Mauri","sequence":"first","affiliation":[{"name":"Institute of Applied Microbiology, RWTH Aachen University , Aachen 52074 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