Genetic and bioprocess engineering to improve squalene production in Yarrowia lipolytica

Huan Liu, Fang Wang, Li Deng, Peng Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


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.

Original languageEnglish
Article number123991
JournalBioresource Technology
StatePublished - Dec 2020
Externally publishedYes


  • Mannitol cycle
  • Metabolic engineering
  • Mevalonate pathway
  • Oleaginous yeast
  • Squalene


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