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The unusual \u03b3\u2010linkage 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\u2010conventional yeast <jats:italic>Yarrowia lipolytica<\/jats:italic> for efficient \u03b3\u2010GC synthesis. The yeast was first converted into a \u03b3\u2010GC producer by disruption of gene <jats:italic>GSH2<\/jats:italic> encoding GSH synthase and by constitutive expression of <jats:italic>GSH1<\/jats:italic> encoding glutamylcysteine ligase. Subsequently genes involved in cysteine and glutamate anabolism, namely <jats:italic>MET4<\/jats:italic>, <jats:italic>CYSE<\/jats:italic>, <jats:italic>CYSF<\/jats:italic>, and <jats:italic>GDH1<\/jats:italic> were overexpressed with the aim to increase their intracellular availability. With such a strategy, a \u03b3\u2010GC titer of 464\u00a0nmol\u00a0mg<jats:sup>\u22121<\/jats:sup> protein (93\u00a0mg\u00a0gDCW<jats:sup>\u22121<\/jats:sup>) was obtained within 24\u00a0h of cell growth.<\/jats:p>","DOI":"10.1002\/biot.202300564","type":"journal-article","created":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T21:10:30Z","timestamp":1708895430000},"source":"Crossref","is-referenced-by-count":3,"title":["Biosynthesis of the antioxidant \u03b3\u2010glutamyl\u2010cysteine with engineered <i>Yarrowia lipolytica<\/i>"],"prefix":"10.1002","volume":"19","author":[{"given":"Diem","family":"Do","sequence":"first","affiliation":[{"name":"Microbial Processes and Interactions TERRA Teaching and Research Centre Gembloux Agro\u2010Bio Tech, University of Liege  Gembloux Belgium"},{"name":"Dong Thap Medical College  Cao Lanh City Dong Thap Province 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