Mitochondrial Engineering of Yarrowia lipolytica for Sustainable Production of α-Bisabolene from Waste Cooking Oil

作者：Kun Yan Zhu, Baixiang Zhao, Yahui Zhang, Jing Kong, Lanxin Rong, Shiqi Liu, Yaping Wang, Cuiying Zhang, Dongguang Xiao, Jee Loon Foo, Aiqun Yu · 发表于：ACS Sustainable Chemistry & Engineering · 年份：2022 · DOI：10.1021/acssuschemeng.2c03063 · 被引用次数：33 · 研究领域：Microbial Metabolic Engineering and Bioproduction、Plant biochemistry and biosynthesis、Enzyme Catalysis and Immobilization

Metabolic engineering of yeasts for terpenoid production has mostly focused on the cytoplasm, whereas harnessing their organelles as subcellular factories has been overlooked. Herein, the farnesyl diphosphate synthetic pathway and α-bisabolene synthase were compartmentalized into the oleaginous yeast Yarrowia lipolytica’s mitochondria to enable high-level α-bisabolene production. Through comprehensive metabolic engineering approaches, we exploited the potential and capability of the mitochondria as a subcellular factory to achieve 257.4 mg/L of α-bisabolene production from glucose. By combining mitochondrial and cytoplasmic engineering, we further boosted the α-bisabolene titer to 765.1 mg/L by utilizing waste cooking oil as the sole carbon source. Finally, the α-bisabolene titer of the resulting strain reached 1058.1 mg/L in a 5 L bioreactor, which is the highest titer in the engineered Y. lipolytica cell factory reported to date. Overall, our study has provided valuable insights into the mitochondrial engineering of Y. lipolytica for sustainable and green production of valuable compounds.