Abstract
Reduced glutathione (GSH), the abundant bioactive tripeptide in most living cells, is widely used in pharmaceutical, food, and cosmetic industries. Specific growth rate (μ) is a key physiological parameter for GSH high-cell-density cultivation using microbial cell factories. Here, based on a biomass probe, an on-line μ feedback control was developed to regulate glucose feeding rate during the fed-batch phase for overproducing GSH in Saccharomyces cerevisiae. Compared with real-time μ controlled at 0.15/h, μ controlled at 0.2/h achieved yeast dry weight (120 g/L), GSH concentration (1.5 g/L), and intracellular GSH content (1.25%), which improved by 9, 150, and 129.1%, respectively. To our knowledge, this is the first report about on-line μ feedback control for GSH production. On-line μ control led to 59.38 mg/L/h of GSH productivity and 3.52 mg/g of GSH yield on glucose, which improved by 107.6 and 7.2%, respectively, in comparison with those of traditional ethanol feedback control (maintaining ethanol concentration at 1%). Taken together, the on-line μ feedback control is a promising method as an efficient alternative to conventional feed control techniques presently practiced in the GSH industry, and has the potential for the production of other valuable chemicals.
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Xiong, ZQ., Guo, MJ., Chu, J. et al. On-line specific growth rate control for improving reduced glutathione production in Saccharomyces cerevisiae . Biotechnol Bioproc E 20, 887–893 (2015). https://doi.org/10.1007/s12257-015-0018-z
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DOI: https://doi.org/10.1007/s12257-015-0018-z