文献类型：期刊文献

英文题名：Engineering Yarrowia lipolytica for high-level β-elemene production via combinatorial metabolic strategies

作者：Dai, Mingyu[1];Cao, Qingyi[1];Jia, Shuanglong[1];Chen, Jiang[1];Xu, Hui-Ying[1];Ye, Bang-Ce[1];Liu, Wei-Bing[1];Zhou, Ying[1]

机构：[1]East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2025

卷号：10

期号：4

起止页码：1172

外文期刊名：SYNTHETIC AND SYSTEMS BIOTECHNOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001533893300001)】；

基金：This work was supported by Shanghai Municipal Science and Tech-nology Major Project.

语种：英文

外文关键词：beta-elemene; Germacrene A; Sesquiterpene; Metabolic engineering; Yarrowia lipolytica

摘要：beta-Elemene, a pharmacologically active sesquiterpene derived from the traditional Chinese medicinal herb Curcuma wenyujin, exhibits broad-spectrum anti-tumor and anti-inflammatory activities. Currently, its commercial production relies heavily on plant extraction, a process associated with high costs and environmental burdens, limiting industrial scalability. To address these challenges, we developed a metabolically engineered Yarrowia lipolytica strain as an efficient microbial cell factory for de novo Germacrene A biosynthesis, the direct precursor of beta-elemene. Through combinatorial optimization strategies-including (1) mevalonate (MVA) pathway enhancement, (2) copy number amplification of germacrene A synthase (GAS), (3) beta-oxidation pathway reinforcement, and (4) introduction of the isopentenyl utilization pathway (IUP)-we significantly improved beta-elemene production. The engineered strain achieved a titer of 3.08 +/- 0.05 g/L in shake-flask cultures, with a yield of 51.27 +/- 0.75 mg/g glucose, representing a 3.5-fold increase over the parental strain. Our work highlights the potential of Y. lipolytica as a sustainable and scalable platform for high-value sesquiterpene production, offering a viable alternative to plant-derived extraction.