TITLE: “Quantitative flux analysis reveals redistribution of glycolytic pathways in dynamic nutrient environments.”
ABSTRACT: Optimal operation of metabolic fluxes is critical for an organism to be evolutionarily competitive. Textbook glycolysis is a conserved pathway that optimally utilizes carbohydrates for growth. However, it is unclear why some organisms simultaneously possess the parallel Entner-Doudoroff (ED) pathway, which has a lower bioenergetic yield. By integrating stable isotope tracing, mass spectrometry, and mathematical modeling, we measure fluxes of these pathways in near-real time. Here, we identify the benefits of the ED pathway under transitory environments. We utilized these tools for flux analysis to study central carbon metabolism in dynamic nutrient conditions. Specifically, we hypothesized that parallel pathways enable cells to rapidly upshift their overall glycolytic flux to benefit growth in response to sudden nutrient availability. Our studies revealed that parallel yet specialized pathways enable dynamic redistribution of metabolic fluxes that are linked to rapid changes in metabolism and broader biological phenotypes.
