Model-assisted formate dehydrogenase-O (fdoH) gene knockout for enhanced succinate production in Escherichia coli from glucose and glycerol carbon sources

• Published in: Journal of biomolecular structure & dynamics 2016-11, Vol.34 (11), p.2305-2316
• Main Authors: Mienda, Bashir Sajo, Shamsir, Mohd Shahir, Md. Illias, Rosli
• Format: Article
• Language: English
• Subjects: Computational Biology; E. coli genome scale model; Escherichia coli - genetics; Escherichia coli - metabolism; formate dehydrogenase-O (fdoH); Formate Dehydrogenases - genetics; gene deletion; Gene Knockout Techniques; glucose; Glucose - metabolism; glycerol; Glycerol - metabolism; in silico predictions; Metabolic Networks and Pathways; Sequence Deletion; succinate; Succinic Acid - metabolism
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2015.1113387

Succinic acid is an important platform chemical that has broad applications and is been listed as one of the top twelve bio-based chemicals produced from biomass by the US Department of Energy. The metabolic role of Escherichia coli formate dehydrogenase-O (fdoH) under anaerobic conditions in relation to succinic acid production remained largely unspecified. Herein we report, what are to our knowledge, the first metabolic fdoH gene knockout that have enhanced succinate production using glucose and glycerol substrates in E. coli. Using the most recent E. coli reconstruction iJO1366, we engineered its host metabolism to enhance the anaerobic succinate production by deleting the fdoH gene, which blocked H + conduction across the mutant cell membrane for the enhanced succinate production. The engineered mutant strain BMS4 showed succinate production of 2.05 g l −1 (41.2-fold in 7 days) from glycerol and .39 g l −1 (6.2-fold in 1 day) from glucose. This work revealed that a single deletion of the fdoH gene is sufficient to increase succinate production in E. coli from both glucose and glycerol substrates.