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

被引:15
作者
Lu, Zhihui [1 ]
Wang, Yaping [1 ]
Li, Zhuo [1 ]
Zhang, Yahui [1 ]
He, Sicheng [1 ]
Zhang, Ziyuan [1 ]
Leong, Susanna [2 ]
Wong, Adison [2 ]
Zhang, Cui-ying [1 ]
Yu, Aiqun [1 ]
机构
[1] Tianjin Univ Sci & Technol, Coll Biotechnol, State Key Lab Food Nutr & Safety, Key Lab Ind Fermentat Microbiol,Minist Educ,Tianji, Tianjin 300457, Peoples R China
[2] Singapore Inst Technol, Food Chem & Biotechnol Cluster, Singapore 138683, Singapore
关键词
Y; lipolytica; sesquiterpenoid; bisabolene; mevalonate pathway; metabolic engineering; lipid droplet; SACCHAROMYCES-CEREVISIAE; BIOSYNTHESIS; EXPRESSION;
D O I
10.1021/acs.jafc.3c02472
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Bisaboleneis a bioactive sesquiterpene with a wide range of applicationsin food, cosmetics, medicine, and aviation fuels. Microbial productionoffers a green, efficient, and sustainable alternative. In this study,we focused on improving the titers of & alpha;-bisabolene in Yarrowia lipolytica by applying two strategies, (i) optimizingthe metabolic flux of & alpha;-bisabolene biosynthetic pathway and(ii) sequestering & alpha;-bisabolene in lipid droplet, thus alleviatingits inherent toxicity to host cells. We showed that overexpressionof DGA1 and OLE1 to increase lipidcontent and unsaturated fatty acid levels was essential for boostingthe & alpha;-bisabolene synthesis when supplemented with auxiliarycarbon sources. The final engineered strain Po1g & alpha;B10 produced1954.3 mg/L & alpha;-bisabolene from the waste cooking oil under shakeflask fermentation, which was 96-fold higher than the control strainPo1g & alpha;B0. At the time of writing, our study represents the highestreported & alpha;-bisabolene titer in the engineered Y. lipolytica cell factory. This work describes novel strategies to improve thebioproduction of & alpha;-bisabolene that potentially may be applicablefor other high-value terpene products.
引用
收藏
页码:11534 / 11543
页数:10
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