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This study seeks to enhance microbial production of gastrodin through high\u2010throughput screening (HTS) and transcriptomics\u2010guided optimization. Initially, atmospheric pressure and room temperature plasma (ARTP)\u2010mediated mutagenesis were employed to develop a library of mutant strains. Furthermore, a transcription factor\u2010based biosensor and a high\u2010throughput solid\u2010phase extraction mass spectrometry (HP\u2010SPE\u2010MS) were evaluated to establish an HTS method for gastrodin. Consequently, mutant strain MT8 was isolated, producing 9.8\u2009g\/L of gastrodin in YPD medium, which represents a 55.6% increase compared to the control strain. Next, key genes identified via transcriptomics were overexpressed in strain MT8, with the overexpression of gene <jats:italic>YALI2E01737g<\/jats:italic>, a gene involved in the synthesis of aromatic amino acids, significantly enhancing gastrodin production to reach 10.1\u2009g\/L. In addition, fermentation process optimization further improved gastrodin titer up to 13.1\u2009g\/L in shaking flasks. This study demonstrated the utility of HTS techniques to enhance gastrodin production and paved the way for its future industrial application.<\/jats:p>","DOI":"10.1002\/bit.28977","type":"journal-article","created":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T10:54:52Z","timestamp":1742640892000},"page":"1484-1495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Engineering <i>Yarrowia lipolytica<\/i> for Enhanced Gastrodin Production via High\u2010Throughput Screening and Transcriptomics\u2010Guided Optimization"],"prefix":"10.1002","volume":"122","author":[{"given":"Mengchen","family":"Hu","sequence":"first","affiliation":[{"name":"School of Food Science and Pharmaceutical Engineering Nanjing Normal University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"He","sequence":"additional","affiliation":[{"name":"School of Food Science and Pharmaceutical 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