Enhancing Precursor Supply and Engineering Efflux Systems to Improve Abscisic Acid Production and Secretion in Yarrowia lipolytica

作者：Mei-Li Sun, Yun Xu, Lu Lin, Jian Gao, Rodrigo Ledesma‐Amaro, Kaifeng Wang, Xiao‐Jun Ji · 发表于：Journal of Agricultural and Food Chemistry · 年份：2025 · DOI：10.1021/acs.jafc.4c10772 · 被引用次数：10 · 研究领域：Microbial Metabolic Engineering and Bioproduction、Enzyme Catalysis and Immobilization、Chemical and Physical Properties in Aqueous Solutions

Abscisic acid is a sesquiterpene phytohormone with extensive applications in agriculture and human health. Currently, it is produced through fermentation of Botrytis cinerea, a plant pathogenic filamentous fungus. The process requires morphology controls, which complicates production and strain optimization. In this study, the abscisic acid production strain Yarrowia lipolytica SM309 was optimized by enhancing the precursor supply using a “push–pull–restrain” strategy focusing on acetyl-CoA, which increased abscisic acid production from 266.34 to 328.51 mg/L. Subsequently, in silico prediction and analysis were used to obtain the docking conformations and binding affinity of ABC transporters for abscisic acid. Overexpression of ABC transporter Yl Gcn20 further enhanced abscisic acid production by 10.88%, reaching 354.21 mg/L. Additionally, low temperature and dodecane addition were employed as auxiliary strategies to promote abscisic acid synthesis, resulting in a titer of 605.92 mg/L. Finally, the engineered strain achieved an abscisic acid titer of 2056.64 mg/L in a 5 L bioreactor, representing the highest titer reported for a yeast de novo synthesis system to date.