Engineering ergothioneine production in Yarrowia lipolytica

FEBS Lett. 2022 May;596(10):1356-1364. doi: 10.1002/1873-3468.14239. Epub 2021 Dec 5.


Ergothioneine is a naturally occurring antioxidant that has shown potential in ameliorating neurodegenerative and cardiovascular diseases. In this study, we investigated the potential of the Crabtree-negative, oleaginous yeast Yarrowia lipolytica as an alternative host for ergothioneine production. We expressed the biosynthetic enzymes EGT1 from Neurospora crassa and EGT2 from Claviceps purpurea to obtain 158 mg·L-1 of ergothioneine in small-scale cultivation, with an additional copy of each gene improving the titer to 205 mg·L-1 . The effect of phosphate limitation on ergothioneine production was studied, and finally, a phosphate-limited fed-batch fermentation in 1 L bioreactors yielded 1.63 ± 0.04 g·L-1 ergothioneine in 220 h, corresponding to an overall volumetric productivity of 7.41 mg·L-1 ·h-1 , showing that Y. lipolytica is a promising host for ergothioneine production.

Keywords: Yarrowia lipolytica; ergothioneine; metabolic engineering; nutraceutical; phosphate-limitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors
  • Ergothioneine*
  • Fermentation
  • Metabolic Engineering
  • Phosphates
  • Yarrowia* / genetics


  • Phosphates
  • Ergothioneine

Associated data

  • RefSeq/XP_956324.3
  • RefSeq/CCE33140.1