An analysis of the concentration change of intermediate metabolites by gene manipulation in fatty acid biosynthesis

In this report, concentration of malonic acid and acetic acid produced in Escherichia coli were investigated by the expression of acetyl-CoA carboxylase genes (accs) and a malonyl-CoA:ACP transacylase gene (fabD). Both malonyl-CoA and acetyl-CoA are essential intermediate metabolites in the fatty acid biosynthetic pathway, and are reversibly transformed to malonic acid and acetic acid, respectively in the cell. Acetyl-CoA is converted to malonic-CoA by acetyl-CoA carboxylases (Accs), which are composed of 3 different subunits (AccA, AccB, and AccC), and the resulting malonyl-CoA is then converted to malonyl-[acp] by malonyl-CoA:ACP transacylase (FabD). In this study, these genes were separately cloned, and the influences of overexpression of 4 different genes on the concentration of malonic acid and acetic acid were analyzed. Compared with the wild type E. coli, a recombinant strain containing 3 acc genes together showed a 41.03% enhanced malonic acid production, and a 4.29-fold increased ratio of malonic acid to acetic acid.

► Acetyl-CoA carboxylase genes (accs) and a malonyl-CoA:ACP transacylase gene (fabD) were separately cloned.
► The influences of partial overexpression of 4 different genes on the concentrations of malonic acid and acetic acid were analyzed.
► The influence of an expression of acc genes on the production ratio of 2 principal organic acids (e.g., malonic acid and acetic acid) was investigated.