High yield production of four-carbon dicarboxylic acids by metabolically engineered Escherichia coli.
Several metabolic engineered Escherichia coli strains were constructed and evaluated for four-carbon dicarboxylic acid production. Fumarase A, fumarase B and fumarase C single, double and triple mutants were constructed in a ldhA adhE mutant background overexpressing the pyruvate carboxylase from Lactococcus lactis. All the mutants produced succinate as the main four-carbon (C4) dicarboxylic acid product when glucose was used as carbon source with the exception of the fumAC and the triple fumB fumAC deletion strains, where malate was the main C4-product with a yield of 0.61-0.67 mol (mole glucose)-1. Additionally, a mdh mutant strain and a previously engineered high-succinate-producing strain (SBS550MG-Cms pHL413-Km) were investigated for aerobic malate production from succinate. These strains produced 40.38 mM (5.41 g/L) and 50.34 mM (6.75 g/L) malate with a molar yield of 0.53 and 0.55 mol (mole succinate)-1, respectively. Finally, by exploiting the high-succinate production capability, the strain SBS550MG-Cms243 pHL413-Km showed significant malate production in a two-stage process from glucose. This strain produced 133 mM (17.83 g/L) malate in 47 h, with a high yield of 1.3 mol (mole glucose)-1 and productivity of 0.38 g L-1 h-1.
['Martinez|Irene|I|', 'Gao|Haijun|H|', 'Bennett|George N|GN|', 'San|Ka-Yiu|KY|0000-0002-1449-4406']
D000426:Alcohol Dehydrogenase D002244:Carbon D003998:Dicarboxylic Acids D004926:Escherichia coli D005649:Fumarate Hydratase D005947:Glucose D007770:L-Lactate Dehydrogenase D013294:Lactococcus lactis D008293:Malates D060847:Metabolic Engineering D009154:Mutation D019802:Succinic Acid
Dicarboxylic acids Metabolic engineering Escherichia coli Succinate Malate