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A two-stage oxygen supply strategy for enhanced l-arginine production by Corynebacterium crenatum based on metabolic fluxes analysis
Authors:Hong Xu  Wenfang Dou  Hongyu Xu  Xiaomei Zhang  Zhiming Rao  Zhongping Shi  Zhenghong Xu
Institution:1. Lab of Pharmaceutical Engineering, School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, 214122, China;2. The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China;1. The Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA;2. Department of Biology, West Chester University of Pennsylvania, West Chester, PA 19383, USA;3. Department of Physiology, Fudan University School of Medicine, Shanghai, China;1. Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK;2. CNRS and Univ. Paris Sud, Glycochimie Moléculaire et Macromoléculaire, ICMMO, UMR 8182, Orsay F-91405, France;3. Centre de Recherche de Gif, Istitut de Chimie des Substances Naturelles du CNRS, Avenue de la Terrasse, F-91198 Gif-sur-Yvette, France;4. Institut de Chimie des Milieux et Matériaux de Poiteirs, UMR 7285, Equipe , 4 rue Michel Brunet, Poitiers, F-8602, France;5. UPMC Univ Paris 06, Institut Universitaire de France, Institut Parisien de Chimie Moléculaire, UMR-CNRS 7201, C. 181, 4 place Jussieu, 75005 Paris, France;1. Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea;2. Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;3. Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;4. College of Life sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea;5. Department of Bio and Fermentation Convergence, Kookmin University, Seoul 136-702, Republic of Korea;1. State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China;2. The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China;3. Laboratory of Food Microbial-Manufacturing Engineering, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China;4. Biotechnology Institute, Laiwu College for Vocational Technology, Laiwu, Shandong 271100, China;1. School of Lifescience, Taizhou University, 1139 Shifu Road, Taizhou 318000, China;2. Zhejiang Hisun Pharmaceutical Co. Ltd., Taizhou 318000, China
Abstract:In this study, the metabolic flux distribution analysis of a new l-arginine (Arg) overproducing strain, Corynebacterium crenatum, was carried out under various oxygen supply conditions in order to explore the optimized oxygen supply profile. The metabolic flux analysis indicated that a relatively higher l-arginine production could be obtained under high oxygen supply (HOS) condition overall. However, during the late fermentation phases, a much more stable l-arginine production could be rather achieved under medium oxygen supply (MOS) condition. As a result, a two-stage oxygen supply strategy, which maintained HOS condition during early fermentation phase, and then step-wisely reduced agitation to keep a stable, smooth and moderate dissolve oxygen levels (DO) changing profile throughout the production phases, was proposed. With the proposed control strategy, the final l-arginine concentration of the batch fermentation was largely increased and reached to a high level of 36.6 g L?1, which was 16% and 51% higher than those obtained under the HOS and MOS conditions. The two-stage oxygen supply strategy could also accelerate glucose consumption rate and thus shorten fermentation time under the same batch initial fermentation condition. The relevant metabolic flux analysis verified the effectiveness of the proposed control strategy.
Keywords:
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