杰马克林
榄香烯
倍半萜
青蒿
化学
生物技术
生物
生物化学
有机化学
细胞凋亡
青蒿素
疟疾
免疫学
恶性疟原虫
作者
Wenjuan Li,Jie Mai,Lu Lin,Zhigang Zhang,Rodrigo Ledesma‐Amaro,Weiliang Dong,Xiao‐Jun Ji
摘要
Beta-elemene, a class of sesquiterpene derived from the Chinese medicinal herb Curcuma wenyujin, is widely used in clinical medicine due to its broad-spectrum antitumor activity. However, the unsustainable plant extraction prompted the search for environmentally friendly strategies for β-elemene production. In this study, we designed a Yarrowia lipolytica cell factory that can continuously produce germacrene A, which is further converted into β-elemene with 100% yield through a Cope rearrangement reaction by shifting the temperature to 250°C. First, the productivity of four plant-derived germacrene A synthases was evaluated. After that, the metabolic flux of the precursor to germacrene A was maximized by optimizing the endogenous mevalonate pathway, inhibiting the competing squalene pathway, and expressing germacrene A synthase gene in multiple copies. Finally, the most promising strain achieved the highest β-elemene titer reported to date with 5.08 g/L. This sustainable and green method has the potential for industrial β-elemene production.
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