Metabolic engineering of Escherichia coli W3110 for efficient production of homoserine from glucose |
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| Institution: | 1. Department of Chemical and Biomolecular Engineering, The University of Tennessee, Knoxville, TN, USA;2. Center of Bioenergy Innovation, Oak Ridge National Laboratory, Oak Ridge, TN, USA;3. Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, 37830, USA;4. Department of Biological Engineering, Konkuk University, Seoul, South Korea;1. Institute of Synthetic Biology, Biomedical Center, Guangdong Province Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China;2. School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China;1. Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA;2. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St. Louis, Saint Louis, MO, 63110, USA;3. Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, Saint Louis, MO, 63110, USA;4. Mass Spectrometry Resource, Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA;5. Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, Saint Louis, MO, 63110, USA;6. Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA;7. Institute of Materials Science & Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA;1. Junior Research Group Synthetic Microbiology, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Beutenbergstr. 11a, 07745, Jena, Germany;2. Core Facility Flow Cytometry, Leibniz Institute on Aging – Fritz Lipmann Institute, Beutenbergstr. 11, 07745, Jena, Germany |
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| Abstract: | Efficient microbial cell factory for the production of homoserine from glucose has been developed by iterative and rational engineering of Escherichia coli W3110. The whole pathway from glucose to homoserine was divided into three groups, namely, glucose transport and glycolysis (‘up-stream’), TCA and glyoxylate cycles (‘mid-stream’), and homoserine module (conversion of aspartate to homoserine and its secretion; ‘down-stream’), and the carbon flux in each group as well as between the groups were accelerated and balanced. Altogether, ∼18 genes were modified for active and consistent production of homoserine during both the actively-growing and non-growing stages of cultivation. Finally, fed-batch, two-stage bioreactor experiments, separating the growth from the production stage, were conducted for 61 h, which gave the high titer of 110.8 g/L, yield of 0.64 g/g glucose and volumetric productivity of 1.82 g/L/h, with an insignificant amount of acetate (<0.5 g/L) as the only noticeable byproduct. The metabolic engineering strategy employed in this study should be applicable for the biosynthesis of other amino acids or chemicals derived from aspartic acid. |
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| Keywords: | L-homoserine production Pathway engineering Two-stage fermentation |
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