Model-assisted formate dehydrogenase-O (fdoH) gene knockout for enhanced succinate production in Escherichia coli from glucose and glycerol carbon sources.
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.
a Bioinformatics Research Group (BIRG), Faculty of Biosciences and Medical Engineering, Department of Biosciences and Health Sciences , Universiti Teknologi Malaysia , Skudai Johor Bahru 81310 , Malaysia.
Bashir Sajo
BS
Mienda
a Bioinformatics Research Group (BIRG), Faculty of Biosciences and Medical Engineering, Department of Biosciences and Health Sciences , Universiti Teknologi Malaysia , Skudai Johor Bahru 81310 , Malaysia.
Mohd Shahir
MS
Shamsir
b Faculty of Chemical Engineering, Department of Bioprocess Engineering , Universiti Teknologi Malaysia , Skudai, Johor Bahru 81310 , Malaysia.
Rosli
R
Md Illias
D019295:Computational Biology; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D005560:Formate Dehydrogenases / Q000235:genetics*; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D017384:Sequence Deletion; D019802:Succinic Acid / Q000378:metabolism*
D019802:Succinic Acid; D005560:Formate Dehydrogenases; C082517:formate dehydrogenase-O; D005947:Glucose; D005990:Glycerol
E. coli genome scale model; formate dehydrogenase-O (fdoH); gene deletion; glucose; glycerol; in silico predictions; succinate