Affiliation:
1. grid.13402.34 0000 0004 1759 700X Key Laboratory of Biomass Chemical Engineering (Education Ministry), College of Chemical and Biological Engineering Zhejiang University 310027 Hangzhou China
2. grid.13402.34 0000 0004 1759 700X College of Chemical and Biological Engineering, Institute of Biological Engineering Zhejiang University 310027 Hangzhou China
3. grid.216417.7 0000 0001 0379 7164 Xiangya International Academy of Translational Medicine Central South University 410013 Changsha Hunan China
4. grid.13402.34 0000 0004 1759 700X Center for Synthetic Biology, College of Chemical and Biological Engineering Zhejiang University 310027 Hangzhou China
Abstract
Abstract
Glutathione is a bioactive tripeptide composed of glycine, l-cysteine, and l-glutamate, and has been widely used in pharmaceutical, food, and healthy products. The current metabolic studies of glutathione were mainly focused on the native producing strains with precursor amino acid supplementation. In the present work, Corynebacterium glutamicum, a workhorse for industrial production of a series of amino acids, was engineered to produce glutathione. First, the introduction of glutathione synthetase gene gshF from Streptococcus agalactiae fulfilled the ability of glutathione production in C. glutamicum and revealed that l-cysteine was the limiting factor. Then, considering the inherent capability of l-glutamate synthesis and the availability of external addition of low-cost glycine, l-cysteine biosynthesis was enhanced using a varieties of pathway engineering methods, such as disrupting the degradation pathways of l-cysteine and l-serine, and removing the repressor responsible for sulfur metabolism. Finally, the simultaneously introduction of gshF and enhancement of cysteine formation enabled C. glutamicum strain to produce glutathione greatly. Without external addition of l-cysteine and l-glutamate, 756 mg/L glutathione was produced. This is first time to demonstrate the potential of the glutathione non-producing strain C. glutamicum for glutathione production and provide a novel strategy to construct glutathione-producing strains.
Funder
National Natural Science Foundation of China
National Key Technology Research & Development Program of The Ministry of Science & Technology of China
Natural Science Foundation of Zhejiang Province
Fundamental Research Funds for the Central Universities
Publisher
Oxford University Press (OUP)
Subject
Applied Microbiology and Biotechnology,Biotechnology,Bioengineering
Cited by
9 articles.
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