ArticleMicrobial cell factories2015
Three-pathway combination for glutathione biosynthesis in Saccharomyces cerevisiae.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 41 citations in OpenAlex.
- Systems metabolic engineering of glutathione biosynthesis inEngineering microbiology · 2025Article
- Enzymes Drive Glutathione Shunt to Explain Oxidative State Using an In-Parallel Multi-Omic Method.International journal of molecular sciences · 2025Article
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- Characterization of MAP c21873-1 as a new counter-selectable marker for unmarked genetic modification of Pichia pastoris.Microbial cell factories · 2024Article
- The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre-insertion and post-insertion methods for brain delivery in normal mice.IET nanobiotechnology · 2023Article
- Metabolic engineering of the L-serine biosynthetic pathway improves glutathione production in Saccharomyces cerevisiae.Microbial cell factories · 2022Article
- Efficient production of glutathione with multi-pathway engineering in Corynebacterium glutamicum.Journal of industrial microbiology & biotechnology · 2019Article
- Article
- Role of bitter leaf (International journal of veterinary science and medicine · 2018Article
- Acrolein-stressed threshold adaptation alters the molecular and metabolic bases of an engineered Saccharomyces cerevisiae to improve glutathione production.Scientific reports · 2018Article
- Our microbes not only produce antibiotics, they also overproduce amino acids.The Journal of antibiotics · 2017Review
- Optimization of Baker's Yeast Production on Date Extract Using Response Surface Methodology (RSM).Foods (Basel, Switzerland) · 2017Article
- Production of valuable compounds by molds and yeasts.The Journal of antibiotics · 2017Review
- Enzymatic improvement of mitochondrial thiol oxidase Erv1 for oxidized glutathione fermentation by Saccharomyces cerevisiae.Microbial cell factories · 2017Article
- Engineering Saccharomyces cerevisiae with the deletion of endogenous glucosidases for the production of flavonoid glucosides.Microbial cell factories · 2016Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlutathione (GSH), a pivotal non-protein thiol, can be biosynthesized through three pathways in different organisms: (1) two consecutive enzymatic reactions catalyzed by γ-glutamylcysteine synthetase (Gsh1 or GshA) and glutathione synthetase (Gsh2 or GshB); (2) a bifunctional γ-glutamylcysteine synthetase/glutathione synthetase (GshF); (3) an alternative condensation of γ-glutamyl phosphate synthesized by γ-glutamyl kinase (Pro1 or ProB) with cysteine to form γ-glutamylcysteine which was further conjugated to glycine by glutathione synthetase. The Gsh1 and Gsh2 of conventional GSH biosynthetic pathway or the bifunctional GshF reported previously have been independently modulated for GSH production. This study developed a novel three-pathway combination method to improve GSH production in Saccharomyces cerevisiae.
resultsA bifunctional enzyme GshF of Actinobacillus pleuropneumoniae was functionally expressed in S. cerevisiae and Pro1 in proline biosynthetic pathway was exploited for improving GSH yield. Moreover, two fusion proteins Gsh2-Gsh1 and Pro1-GshB were constructed to increase the two-step coupling efficiency of GSH synthesis by mimicking the native domain fusion of GshF. The engineered strain W303-1b/FGP with three biosynthetic pathways presented the highest GSH concentration (216.50 mg/L) and GSH production of W303-1b/FGP was further improved by 61.37 % when amino acid precursors (5 mM glutamic acid, 5 mM cysteine and 5 mM glycine) were fed in shake flask cultures. In batch culture process, the recombinant strain W303-1b/FGP also kept high efficiency in GSH production and reached an intracellular GSH content of 2.27 % after 24-h fermentation.
conclusionsThe engineered strains harbouring three GSH pathways displayed higher GSH producing capacity than those with individually modulated pathways. Three-pathway combinatorial biosynthesis of GSH promises more effective industrial production of GSH using S. cerevisiae.
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