Co‐production of γ ‐glutamylcysteine and glutathione by mutant strain Saccharomyces cerevisiae FC‐3 and its kinetic analysis

Abstract

Co-production of gamma -glutamylcysteine (gamma -GC) and glutathione (GSH) by a novel mutant strain Saccharomyces cerevisiae FC-3 and its kinetic analysis were investigated. The strain could produce gamma -GC and GSH with high yields (4.22 and 14.3 mg/g-DCW, respectively) in batch submerged cultures. Effects of medium components and cultivation conditions on cell growth and the contents of intracellular gamma -GC and GSH were examined. Results show that 2% (w/v) sucrose and 2.5% (w/v) yeast extract are the best carbon and nitrogen sources, respectively, and supplement of three amino acids (glycine, cysteine and glutamate), each at 0.08% (w/v), in the medium could enhance gamma -GC and GSH production. In addition, optimal operating conditions are at the initial pH value of 7.0, 30 degrees C and 200 rev/min. Moreover, results obtained from kinetic analyses reveal that gamma -GC production is mixed-type growth associated, but GSH production is growth-associated.

Biosynthesis of the antioxidant γ‐glutamyl‐cysteine with engineered Yarrowia lipolytica

“…In S. cerevisiae, the best mutants obtained by chemical mutagenesis produce a mixture of γ-GC and GSH, with a γ-GC titer of less than 5 mg gDCW −1 . [42,43] Herein, Y. lipolytica has been engineered to produce γ-GC, not GSH, with a titer of 464 nmol mg −1 protein, which corresponds to 93 mg gDCW −1 within 24 h.…”

Involvement of Sulfur in the Biosynthesis of Essential Metabolites in Pathogenic Fungi of Animals, Particularly Aspergillus spp.: Molecular and Therapeutic Implications

“…Cys is converted to GSH via a two-step pathway in fungi (Schmacht et al, 2017). The first step is likely catalyzed by glutamate-cysteine ligase (Gcs1), which catalyzes the condensation of Cys and glutamate to form γ-glutamylcysteine, which is then converted to GSH by the addition of Gly to the C-terminal of γ-glutamylcysteine by glutathione synthase (Gsh2) (Chen et al, 2009). Moreover, both Cys and pantothenic acid are key precursors of the thiol-containing Coenzyme A in yeast, and in other fungi (Chiu et al, 2019).…”