Study summary · research use only
Engineering Escherichia coli for efficient glutathione production
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study engineered Escherichia coli (bacteria) for glutathione production by overexpressing gshA and gshB, encoding cysteine glutamate ligase and glutathione synthetase, producing 4.3 g/L glutathione, mostly excreted into the culture medium. Further modifications, including inhibiting degradation (Δggt and ΔpepT), deleting gor (Δgor), attenuating glutathione uptake (ΔyliABCD), and enhancing cysteine production (PompF-cysE), produced the engineered strain KG06, which yielded 19.6 g/L glutathione after 48 h of fed-batch fermentation with continuous ammonium sulfate addition; continuous glycine feeding was also reported as important. Metabolic flux and metabolomic analyses suggested conversion of O-acetylserine to cysteine was rate-limiting, and adding sodium thiosulfate raised the titer to 22.0 g/L, described as the first report of glutathione fermentation without added cysteine in E. coli.
Abstract
Glutathione is a tripeptide of excellent value in the pharmaceutical, food, and cosmetic industries that is currently produced during yeast fermentation. In this case, glutathione accumulates intracellularly, which hinders high production. Here, we engineered Escherichia coli for the efficient production of glutathione. A total of 4.3 g/L glutathione was produced by overexpressing gshA and gshB, which encode cysteine glutamate ligase and glutathione synthetase, respectively, and most of the glutathione was excreted into the culture medium. Further improvements were achieved by inhibiting degradation (Δggt and ΔpepT); deleting gor (Δgor), which encodes glutathione oxide reductase; attenuating glutathione uptake (ΔyliABCD); and enhancing cysteine production (PompF-cysE). The engineered strain KG06 produced 19.6 g/L glutathione after 48 h of fed-batch fermentation with continuous addition of ammonium sulfate as the sulfur source. We also found that continuous feeding of glycine had a crucial role for effective glutathione production. The results of metabolic flux and metabolomic analyses suggested that the conversion of O-acetylserine to cysteine is the rate-limiting step in glutathione production by KG06. The use of sodium thiosulfate largely overcame this limitation, increasing the glutathione titer to 22.0 g/L, which is, to our knowledge, the highest titer reported to date in the literature. This study is the first report of glutathione fermentation without adding cysteine in E. coli. Our findings provide a great potential of E. coli fermentation process for the industrial production of glutathione.
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