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Updated: Dec 11, 2025
Genetic Engineering of an Unconventional Yeast for Renewable Biofuel and Biochemical Production
Published on: September 20, 2016
Genetic and bioprocess engineering to improve squalene production in Yarrowia lipolytica
Huan Liu1, Fang Wang2, Li Deng2
1Department of Chemical, Biochemical and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD 21250, China; College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Abstract:
Squalene 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.
