Model-aided atpE gene knockout strategy in Escherichia coli for enhanced succinic acid production from glycerol |
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Authors: | Bashir Sajo Mienda Mohd Shahir Shamsir Rosli Md Illias |
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Institution: | 1. Bioinformatics Research Group (BIRG), Faculty of Biosciences and Medical Engineering, Department of Biosciences and Health Sciences, Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru, Malaysia;2. Faculty of Chemical Engineering, Department of Bioprocess Engineering, Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru, Malaysia |
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Abstract: | Succinic acid is an important platform chemical with a variety of applications. Model-guided metabolic engineering strategies in Escherichia coli for strain improvement to increase succinic acid production using glucose and glycerol remain largely unexplored. Herein, we report what are, to our knowledge, the first metabolic knockout of the atpE gene to have increased succinic acid production using both glucose and alternative glycerol carbon sources in E. coli. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic production of succinic acid by deleting the atpE gene, thereby generating additional reducing equivalents by blocking H+ conduction across the mutant cell membrane. This strategy produced 1.58 and .49 g l?1 of succinic acid from glycerol and glucose substrate, respectively. This work further elucidates a model-guided and/or system-based metabolic engineering, involving only a single-gene deletion strategy for enhanced succinic acid production in E. coli. |
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Keywords: | model-guided F0 sector of membrane-bound ATP synthase (atpE) gene knockout E coli succinic acid glycerol metabolic engineering OptFlux |
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