[en] The dipeptide γ-glutamylcysteine (γ-GC), the first intermediate of glutathione (GSH) synthesis, is considered as a promising drug to reduce or prevent plethora of age-related disorders such as Alzheimer and Parkinson diseases. The unusual γ-linkage between the two constitutive amino acids, namely cysteine and glutamate, renders its chemical synthesis particularly challenging. Herein, we report on the metabolic engineering of the non-conventional yeast Yarrowia lipolytica for efficient γ-GC synthesis. The yeast was first converted into a γ-GC producer by disruption of gene GSH2 encoding GSH synthase and by constitutive expression of GSH1 encoding glutamylcysteine ligase. Subsequently genes involved in cysteine and glutamate anabolism, namely MET4, CYSE, CYSF, and GDH1 were overexpressed with the aim to increase their intracellular availability. With such a strategy, a γ-GC titer of 464 nmol mg-1 protein (93 mg gDCW-1 ) was obtained within 24 h of cell growth.
Disciplines :
Biotechnology
Author, co-author :
Do, Diem; Microbial Processes and Interactions, TERRA Teaching and Research Centre, Gembloux Agro-Bio Tech, University of Liege, Gembloux, Belgium ; Dong Thap Medical College, Cao Lanh City, Dong Thap Province, Vietnam
Guruk, Mümine ; Université de Liège - ULiège > TERRA Research Centre ; Department of Food Engineering, Faculty of Engineering, Cukurova University, Adana, Turkey
Kus-Liśkiewicz, Małgorzata; Institute of Biotechnology, College of Natural Sciences, University of Rzeszow, Rzeszow, Poland
Damblon, Christian ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique structurale
Arguelles-Arias, Anthony; Microbial Processes and Interactions, TERRA Teaching and Research Centre, Gembloux Agro-Bio Tech, University of Liege, Gembloux, Belgium
Erten, Huseyin; Department of Food Engineering, Faculty of Engineering, Cukurova University, Adana, Turkey
Fickers, Patrick ; Université de Liège - ULiège > TERRA Research Centre > Microbial technologies
Language :
English
Title :
Biosynthesis of the antioxidant γ-glutamyl-cysteine with engineered Yarrowia lipolytica.
Publication date :
February 2024
Journal title :
Biotechnology Journal
ISSN :
1860-6768
eISSN :
1860-7314
Publisher :
John Wiley and Sons Inc, Germany
Volume :
19
Issue :
2
Pages :
e2300564
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
This research was supported by the TERRA Teaching and Research Centre, University of Liège. The authors acknowledge O. Denies, S. Steels, and G. Balleux for technical assistance.
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