Biosynthesis of the antioxidant γ-glutamyl-cysteine with engineered Yarrowia lipolytica
BIOTECHNOLOGY JOURNAL, cilt.19, sa.2300564, ss.1-9, 2024 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 19 Sayı: 2300564
- Basım Tarihi: 2024
- Doi Numarası: 10.1002/biot.202300564
- Dergi Adı: BIOTECHNOLOGY JOURNAL
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Compendex, EMBASE, MEDLINE, Veterinary Science Database
- Sayfa Sayıları: ss.1-9
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Çukurova Üniversitesi Adresli: Evet
Özet
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 agerelated
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 (93mg gDCW−1) was obtained within 24 h of cell growth.