ArcA overexpression induces fermentation and results in enhanced growth rates of E. coli.

Overflow metabolism in the presence of oxygen occurs at fast growth rates in a wide range of organisms including bacteria, yeast and cancer cells and plays an important role in biotechnology during production of proteins or metabolic compounds. As recently suggested, overflow metabolism can be understood in terms of proteome allocation, since fermentation has lower proteome cost for energy production than respiration. Here, we demonstrate that ArcA overexpression in aerobic conditions, results in downregulation of respiratory pathways and enhanced growth rates on glycolytic substrates of E. coli, coinciding with acetate excretion and increased carbon uptake rates. These results suggest that fermentation enables faster growth and demonstrate that fermentation on many glycolytic carbon sources is not limited by carbon uptake. Hence, these findings are difficult to reconcile with many alternative hypotheses that have been proposed for the origin of overflow metabolism and the growth rate dependence of fermentation and respiration, which are based on limited capacity of respiration or limitations in uptake rates and catabolic pathways. Instead, as suggested by increased lag phases of ArcA overexpression strains, respiratory energy metabolism may be related to a general preparatory response, observed for decreasing growth rates, but with limited advantages for maximizing steady-state growth rate.