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KMID : 1094720150200050887
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Biotechnology and Bioprocess Engineering
2015 Volume.20 No. 5 p.887 ~ p.893
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On-line specific growth rate control for improving reduced glutathione production in Saccharomyces cerevisiae
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Xiong Zhi-Qiang
Guo Mei-Jin
Chu Ju
Zhuang Ying-Ping
Zhang Si-Liang
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Abstract
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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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KEYWORD
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feedback control, fed-batch phase, reduced glutathione, Saccharomyces cerevisiae, specific growth rate
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