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The methanol utilization pathway (MUT) during methanol-based growth plays a crucial role in providing precursors and energy for cell growth and development. This study investigated the impact of boosting the methanol dissimilation pathway, a branch of MUT that plays a vital role in detoxifying formaldehyde and providing energy in the form of NADH, in <jats:italic>K. phaffi<\/jats:italic>. This was achieved by integrating two orthologous genes from <jats:italic>Hansenula polymorpha<\/jats:italic> into the <jats:italic>K. phaffi<\/jats:italic> genome: formaldehyde dehydrogenase (<jats:italic>Hp<\/jats:italic>FLD) and formate dehydrogenase (<jats:italic>Hp<\/jats:italic>FMDH). The <jats:italic>Hp<\/jats:italic>FLD and <jats:italic>Hp<\/jats:italic>FMDH genes were isolated from the <jats:italic>Hansenula polymorpha<\/jats:italic> genome and inserted under the regulation of the pAOX1 promoter in the genome of recombinant <jats:italic>K. phaffi<\/jats:italic> that already contained a single copy of model protein genes (eGFP or EGII). The expression levels of these model proteins were assessed through protein activity assays and gene expression analysis. The findings revealed that while both orthologous genes positively influenced model protein production, <jats:italic>Hp<\/jats:italic>FMDH exhibited a more pronounced upregulation in expression compared to <jats:italic>Hp<\/jats:italic>FLD. Co-expression of both orthologous genes demonstrated synergistic effects, resulting in approximately a twofold increase in the levels of the model proteins detected. This study provides valuable insights into enhancing the production capacity of recombinant proteins in <jats:italic>K. phaffi<\/jats:italic>.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1186\/s13568-024-01743-y","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T18:02:29Z","timestamp":1722621749000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hansenula polymorpha methanol metabolism genes enhance recombinant protein production in Komagataella phaffi"],"prefix":"10.1186","volume":"14","author":[{"given":"Maryam","family":"Khalifeh Soltani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sareh","family":"Arjmand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Omid","family":"Ranaei Siadat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdolreza","family":"Bagheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Hassan","family":"Marashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"issue":"1","key":"1743_CR1","first-page":"108","volume":"3","author":"A Akbarzadeh","year":"2013","unstructured":"Akbarzadeh A, Ranaei Siadat SO, Zamani MR, Motallebi M, Barshan Tashnizi M (2013) Comparison of biochemical properties of recombinant endoglucanase II of Trichoderma reesei in methylotrophic yeasts, Pichia pastoris and Hansenula polymorpha. 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