Liu, HuanWang, FangDeng, LiXu, Peng2020-08-172020-08-172020-08-10Huan Liu, Fang Wang, Li Deng and Peng Xu, Genetic and bioprocess engineering to improve squalene production in Yarrowia lipolytica, Bioresource Technology Volume 317, 123991 (2020), https://doi.org/10.1016/j.biortech.2020.123991https://doi.org/10.1016/j.biortech.2020.123991http://hdl.handle.net/11603/19438Squalene is the precursor for triterpene-based natural products and steroids-based drugs. It has been widely used as pharmaceutical intermediates and personal care products. The aim of this work is to test the feasibility of engineering Yarrowia lipolytica as a potential host for squalene production. The bottleneck of the pathway was removed by overexpressing native HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase. With the recycling of NADPH from the mannitol cycle, the engineered strain produced about 180.3 mg/L and 188.2 mg/L squalene from glucose or acetate minimal media. By optimizing the C/N ratio, controlling the media pH and mitigating acetyl-CoA flux competition from lipogenesis, the engineered strain produced 502.7 mg/L squalene, a 28-fold increase over the parental strain (17.2 mg/L). This work may serve as a baseline to harness Y. lipolytica as an oleaginous cell factory for sustainable production of squalene or terpenoids-based chemicals and natural products.8 pagesen-USThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.Attribution 4.0 InternationalText