Engineering ergothioneine production in Yarrowia lipolytica. Issue 10 (5th December 2021)

• Record Type: Journal Article
• Authors: van der Hoek, Steven A.; Rusnák, Matej; Jacobsen, Irene Hjorth; Martínez, José L.; Kell, Douglas B.; Borodina, Irina
• Is Part Of: FEBS letters. Volume 596:Issue 10(2022)
• Page Start: 1356
• Page End: 1364
• Publication Date: 2021-12-05
• Subjects: ergothioneine -- metabolic engineering -- nutraceutical -- phosphate‐limitation -- Yarrowia lipolytica; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14239
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : Here, we report that the oleaginous yeast Yarrowia lipolytica is a viable host to produce the antioxidant ergothioneine. Yarrowia lipolytica could reach ergothioneine production levels comparable to or exceeding those reported in other hosts, such as Escherichia coli and Saccharomyces cerevisiae, by genomic integration of the ergothioneine biosynthetic pathway and fed‐batch fermentation on mineral medium.