Effects of arcA and arcB genes knockout on the metabolism in Escherichia coli under aerobic condition

The effects of arcA and arcB genes knockout on the metabolism in Escherichia coli were investigated for the aerobic batch and continuous cultivations based on gene expressions, enzyme activities, and the metabolic flux distributions obtained by 13C-labeling experiment. The integration of the different levels of information indicates that arcB gene knockout activated TCA cycle by gene and enzyme levels regulation as compared with the wild type BW25113 under aerobic condition. The TCA cycle was further activated for arcA gene knockout mutant as compared with arcB mutant. Since the TCA cycle is the source of energy for the cell, its activation together with up-regulation of cyoA gene expression is attractive for the improvement of the cell growth and useful metabolite production, etc. The present research shows the reduction of acetate production in arcA/B mutants, which is the common obstacle for useful metabolite production using E. coli. The activation of TCA cycle together with limited respiratory capacity caused NADH accumulation, which in turn repress the TCA cycle activity by enzyme level regulation. This could be released by adding nicotinic acid.