{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:46:38Z","timestamp":1787622398420,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2105900"],"award-info":[{"award-number":["2022YFC2105900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Natural sesquiterpene are valuable compounds with diverse applications in industries, such as cosmetics and energy. Microbial synthesis offers a promising way for sesquiterpene production. Methanol, can be synthesized from CO<jats:sub>2<\/jats:sub> and solar energy, serves as a sustainable carbon source. However, it is still a challenge to utilize methanol for the synthesis of value\u2010added compounds. <jats:italic>Pichia pastoris<\/jats:italic> (syn. <jats:italic>Komagataella phaffii<\/jats:italic>), known for its efficient utilization of glucose and methanol, has been widely used in protein synthesis. With advancements in technology, <jats:italic>P. pastoris<\/jats:italic> is gradually engineered for chemicals production. Here, we successfully achieved the synthesis of \u03b1\u2010bisabolene in <jats:italic>P. pastoris<\/jats:italic> with dual carbon sources by expressing the \u03b1\u2010bisabolene synthase gene under constitutive promoters. We systematically analyzed the effects of different steps in the mevalonate (MVA) pathway when methanol or glucose was used as the carbon source. Our finding revealed that the sesquiterpene synthase module significantly increased the production when methanol was used. While the metabolic modules <jats:italic>MK<\/jats:italic> and <jats:italic>PMK<\/jats:italic> greatly improved carbon source utilization, cell growth, and titer when glucose was used. Additionally, we demonstrated the synthesis of \u03b2\u2010farnesene from dual carbon source by replacing the \u03b1\u2010bisabolene synthase with a \u03b2\u2010farnesene synthase. This study establishes a platform strain that is capable to synthesize sesquiterpene from different carbon sources in <jats:italic>P. pastoris<\/jats:italic>. Moreover, it paves the way for the development of <jats:italic>P. pastoris<\/jats:italic> as a high\u2010efficiency microbial cell factory for producing various chemicals, and lays foundation for large\u2010scale synthesis of high value\u2010added chemicals efficiently from methanol in <jats:italic>P. pastoris<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/biot.202400261","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T09:48:39Z","timestamp":1723110519000},"source":"Crossref","is-referenced-by-count":32,"title":["Engineering a versatile yeast platform for sesquiterpene production from glucose or methanol"],"prefix":"10.1002","volume":"19","author":[{"given":"Linhui","family":"Gao","sequence":"first","affiliation":[{"name":"Division of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian China"},{"name":"Dalian Key Laboratory of Energy Biotechnology, Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian China"},{"name":"Henan Engineering Laboratory for Bioconversion Technology of Functional Microbes, College of Life Sciences Henan Normal University  Xinxiang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian China"},{"name":"Dalian Key Laboratory of Energy Biotechnology, Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian China"},{"name":"University of Chinese Academy of Sciences  Beijing 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