{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:16:07Z","timestamp":1788174967500,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Retinol, a derivative of vitamin A with potent antioxidant and therapeutic properties, is in high market demand. In response to the low productivity of conventional methods, metabolic engineering has been explored for microbial retinol production. However, systematic engineering strategies for high\u2010level retinol synthesis in\n                    <jats:italic>Komagataella phaffii<\/jats:italic>\n                    remain limited. In this study, the methylotrophic yeast\n                    <jats:italic>K. phaffii<\/jats:italic>\n                    was developed as an engineered chassis for efficient de novo retinol biosynthesis. Based on a previously constructed \u03b2\u2010carotene\u2010producing strain, \u03b2\u2010carotene\u201015,15\u2032\u2010dioxygenase (Blh) and retinol dehydrogenase (RDH12) were screened and introduced to establish the synthetic pathway of retinol. To increase precursor supply, key genes in the \u03b2\u2010carotene biosynthetic pathway were overexpressed. The mevalonate (MVA) pathway was further optimized, and central carbon metabolism was reprogrammed to enhance metabolic flux toward retinol. Transport engineering was also performed to improve retinol secretion. Several candidate transporters were overexpressed, and the protein encoded by\n                    <jats:italic>chr1\u20104_0619<\/jats:italic>\n                    in\n                    <jats:italic>K. phaffii<\/jats:italic>\n                    was identified as an endogenous retinol transporter. The final engineered strain produced 3.38\u00a0g\/L retinol with BHT supplementation in fed\u2010batch fermentation using a 1.5 L bioreactor. This work represents de novo microbial synthesis of retinol from a one\u2010carbon feedstock, demonstrating the formidable potential of\n                    <jats:italic>K. phaffii<\/jats:italic>\n                    as a sustainable chassis for retinol production.\n                  <\/jats:p>","DOI":"10.1002\/biot.70288","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:21:39Z","timestamp":1786947699000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Engineering of\n                    <i>Komagataella Phaffii<\/i>\n                    for de Novo Synthesis of Retinol From Methanol"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1788-8012","authenticated-orcid":false,"given":"Yanxuan","family":"Wu","sequence":"first","affiliation":[{"name":"Guangdong Key Laboratory of Fermentation and Enzyme Engineering School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"Guangdong Research Center of Industrial Enzyme and Green Manufacturing Technology School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengan","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Fermentation and Enzyme Engineering School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"Guangdong Research Center of Industrial Enzyme and Green Manufacturing Technology School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuli","family":"Liang","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Fermentation and Enzyme Engineering School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"Guangdong Research Center of Industrial Enzyme and Green Manufacturing Technology School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Fermentation and Enzyme Engineering School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"Guangdong Research Center of Industrial Enzyme and Green Manufacturing Technology School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Fermentation and Enzyme Engineering School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"Guangdong Research Center of Industrial Enzyme and Green Manufacturing Technology School of Biology and Biological Engineering South China University of Technology  Guangzhou China"},{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Fermentation 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