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Recently, we demonstrated that formate derived from the tetrahydrofolate\u2010mediated one\u2010carbon (THF\u2010C1) metabolism accumulates in\n K<\/jats:italic>\n .\n phaffii<\/jats:italic>\n cells deficient in formate dehydrogenase (FdhKO) when grown in sorbitol\u2010based methanol\u2010free medium. Using the lipase CalB from\n Candida antarctica<\/jats:italic>\n as a model protein, we observed that recombinant protein (rProt) productivity in an FdhKO strain grown on sorbitol was comparable to that of an Fdh\u2010proficient strain grown on methanol. However, sorbitol is inefficiently metabolised in\n K<\/jats:italic>\n .\n phaffii<\/jats:italic>\n , leading to a low growth rate and potentially limiting rProt productivity due to insufficient energy and carbon supply. Here, we increased the sorbitol uptake rate, and thus improved sorbitol metabolism, by overexpressing the gene encoding sorbitol dehydrogenase (\n SOR1<\/jats:italic>\n ) in an FdhKO strain. Our results demonstrate that while increased sorbitol metabolism promotes biomass formation, it reduces P\n \n AOX1<\/jats:italic>\n <\/jats:sub>\n induction, as evidenced by lower formate accumulation and decreased rProt productivity, both for intracellular eGFP and secreted proteins namely CalB lipase and glucose oxidase (Gox) from\n Aspergillus niger<\/jats:italic>\n in\n SOR1<\/jats:italic>\n \u2010overexpressing strains. Additionally, oxygen availability for cells influences these dynamics, with lower oxygen transfer favouring higher P\n \n AOX1<\/jats:italic>\n <\/jats:sub>\n induction due to increased formate accumulation in an FdhKO strain. Our data also suggest that at low oxygen transfer and low sorbitol uptake rate, the proportion of cells in an induced state increased significantly. This work provides valuable insights into the interplay between sorbitol metabolism and oxygen transfer conditions, contributing to the development of improved recombinant protein production strategies in\n K<\/jats:italic>\n .\n phaffii<\/jats:italic>\n .\n <\/jats:p>","DOI":"10.1111\/1751-7915.70263","type":"journal-article","created":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T14:01:05Z","timestamp":1762610465000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sorbitol Uptake and Oxygen Transfer Shape\n \n AOX1<\/i>\n <\/scp>\n Promoter Induction in Formate Dehydrogenase\u2010Deficient\n \n Komagataella phaffii<\/i>\n <\/scp>"],"prefix":"10.1111","volume":"18","author":[{"given":"Cristina","family":"Bustos","sequence":"first","affiliation":[{"name":"Microbial Processes and Interactions, TERRA Teaching and Research Centre, Gembloux Agro\u2010Bio Tech University of Liege Gembloux Belgium"},{"name":"School of Biochemical Engineering Pontificia Universidad Cat\u00f3lica de Valpara\u00edso Valparaiso Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5862-595X","authenticated-orcid":false,"given":"Rocio","family":"Cozmar","sequence":"additional","affiliation":[{"name":"Microbial Processes and Interactions, TERRA Teaching and Research Centre, Gembloux Agro\u2010Bio Tech University of Liege Gembloux Belgium"},{"name":"School of Biochemical Engineering Pontificia Universidad Cat\u00f3lica de Valpara\u00edso Valparaiso Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-0023","authenticated-orcid":false,"given":"Julio","family":"Berrios","sequence":"additional","affiliation":[{"name":"School of Biochemical Engineering Pontificia Universidad Cat\u00f3lica de Valpara\u00edso Valparaiso 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