Combining Metabolic Engineering and Lipid Droplet Storage Engineering for Improved α-Bisabolene Production in Yarrowia Lipolytica

• DOI: 10.1021/acs.jafc.3c02472
• Publication Date: 2023-07-18T19:10:41Z
• Authors: Zhihui Lu; Yaping Wang; Zhuo Li; Yahui Zhang; Sicheng He; Ziyuan Zhang; Susanna Leong; Adison Wong; Cui-ying Zhang; Aiqun Yu
• Keywords: Yarrowia; Metabolic Engineering

Bisabolene is a bioactive sesquiterpene with wide range of applications in food, cosmetics, medicine, and aviation fuels. Microbial production offers green, efficient, sustainable alternative. In this study, we focused on improving the titers α-bisabolene Yarrowia lipolytica by applying two strategies, (i) optimizing metabolic flux biosynthetic pathway (ii) sequestering lipid droplet, thus alleviating its inherent toxicity to host cells. We showed that overexpression DGA1 OLE1 increase content unsaturated fatty acid levels was essential for boosting synthesis when supplemented auxiliary carbon sources. The final engineered strain Po1gαB10 produced 1954.3 mg/L from waste cooking oil under shake flask fermentation, which 96-fold higher than control Po1gαB0. At time writing, our study represents highest reported titer Y. cell factory. This work describes novel strategies improve bioproduction potentially may be applicable other high-value terpene products.