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The industrial model yeast\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    (\n                    <jats:italic>S. cerevisiae<\/jats:italic>\n                    ) inherently possesses the mevalonate pathway, which supplies precursors for retinol biosynthesis. However, the imbalanced distribution of metabolic flux between the retinol synthesis pathway and other competing pathways limits the retinol titer. To improve the efficiency of the retinol synthesis pathway, we first identified two key bottleneck enzymes, geranylgeranyl diphosphate synthase (CrtE) and \u03b2\u2010carotene 15,15\u2032\u2010dioxygenase (Blh), and optimized their gene copy numbers, resulting in a 72.0% increase in retinol titer. Subsequently, to reduce the diversion of the metabolic flux toward squalene production, we employed a multidimensional manipulation strategy to regulate the expression of squalene synthase (ERG9). By replacing the native\n                    <jats:italic>ERG9<\/jats:italic>\n                    promoter with P\n                    <jats:italic>\n                      <jats:sub>SPI1<\/jats:sub>\n                    <\/jats:italic>\n                    and using a decompartmentalization strategy, the retinol titer was further increased to 1.41\u00a0g\/L. After auxotrophic marker gene complementation, the resulting retinol titer in a 5\u2010L bioreactor was 7.19\u00a0g\/L, which was the highest reported value in\n                    <jats:italic>S. cerevisiae<\/jats:italic>\n                    . This work establishes an effective engineering strategy for high\u2010yield retinol production in\n                    <jats:italic>S. cerevisiae<\/jats:italic>\n                    , which can facilitate subsequent process development and scale\u2010up.\n                  <\/jats:p>","DOI":"10.1002\/biot.70193","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T07:26:57Z","timestamp":1770362817000},"source":"Crossref","is-referenced-by-count":7,"title":["Multidimensional Engineering of\n                    <i>Saccharomyces cerevisiae<\/i>\n                    for Efficient Production of Retinol"],"prefix":"10.1002","volume":"21","author":[{"given":"Minxia","family":"Song","sequence":"first","affiliation":[{"name":"Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education Jiangnan University  Wuxi China"},{"name":"Science Center for Future Foods Jiangnan University  Wuxi 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Carbohydrate Chemistry and Biotechnology Ministry of Education Jiangnan University  Wuxi China"},{"name":"Science Center for Future Foods Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0562-9647","authenticated-orcid":false,"given":"Yanfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education Jiangnan University  Wuxi China"},{"name":"Science Center for Future Foods Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghua","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education Jiangnan University  Wuxi China"},{"name":"Science Center for Future Foods Jiangnan University  Wuxi 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