Metabolite profiling coupled with metabolic flux analysis reveals physiological and metabolic impacts on Lactobacillus paracasei oxygen metabolism

Abstract

Abstract In this study, the impacts of oxygen metabolism characterized by oxygen uptake rate (OUR) on lactic acid production in Lactobacillus paracasei were investigated through metabolite profiling and metabolic flux analysis. At growth phase, with the cost of declining lactic acid yield, the cells shifted pyruvate metabolism from lactic acid production to ATP high-yielding acetate synthesis to guarantee sufficient energy supply for cell growth under high OUR condition. When the cells reached to stationary phase, significant glucose metabolism inhibition happened with high OUR level due to much more reactive oxygen species (ROS) accumulation in the cells, which subsequently would attack glycolytic key enzyme, glycerate-3-phosphate dehydrogenase (GAPDH), leading to the substantial limitation of glucose consumption. Moreover, other than glucose metabolism restriction, the decline on metabolic level regulation of lactic acid yield further decreased lactic acid productivity. On the other hand, it was interestingly found that intracellular redox balance was greatly dependent on acetyl-CoA node (acetate/ethanol) in growth phase, and acetoin node (acetoin/2,3-butanediol) in stationary phase respectively. The application of integrated metabolite profiling and metabolic flux analysis highlighted the regulation of energy and redox metabolism in lactic acid production by L. paracasei.