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Two-stage oxygen supply strategy for enhanced lipase production by Bacillus subtilis based on metabolic flux analysis
Institution:1. College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 210009, People’s Republic of China;2. College of Food Science and Light Industry, Nanjing Tech University, Nanjing 210009, People’s Republic of China;3. College of Chemical and Molecular Engineering, Nanjing Tech University, Nanjing 210009, People’s Republic of China;4. College of Pharmaceutical Science, Nanjing Tech University, Nanjing 210009, People’s Republic of China;1. Department of Environmental Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China;2. Department of Water Supply and Environmental Engineering, Arba Minch University, P.O. Box 21, Arba Minch, Ethiopia;1. State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, PR China;2. Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, 211816, PR China;3. Key Laboratory of Development and Application of Rural Renewable Energy, Biogas Institute of Ministry of Agriculture, 610041, PR China
Abstract:Lipase production by Bacillus subtilis CICC20034 was assessed by metabolic flux distribution analysis. Lipase production was tested under various oxygen supply conditions in a synthetic medium to obtain the optimal oxygen supply profile. Based on the metabolic flux analysis, a two-stage oxygen supply strategy (TOS) that maintained high oxygen supply conditions during early fermentation phase, and then step-wisely reduced aeration to keep a stable, smooth, and adequate changing dissolved oxygen (DO) level profile throughout the production phases was carried out. With the proposed control strategy, the final lipase activity in batch fermentation significantly increased and reached a high level at 0.56 U/ml, corresponding to a 51% increase. The relevant metabolic flux analysis verified the effectiveness of the proposed control strategy. By applying TOS in composite medium, the final lipase activity reached 5.0 U/ml.
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