Central Carbon Metabolism as a Minimal Biochemical Walk between Precursors for Biomass and Energy

SummaryCentral carbon metabolism uses a complex series of enzymatic steps to convert sugars into metabolic precursors. These precursors are then used to generate the entire biomass of the cell. Are there simplifying principles that can explain the structure of such metabolic networks? Here we address this question by studying central carbon metabolism in E. coli. We use all known classes of enzymes that work on carbohydrates to generate rules for converting compounds and for generating possible paths between compounds. We find that central carbon metabolism is built as a minimal walk between the 12 precursor metabolites that form the basis for biomass and one precursor essential for the positive net ATP balance in glycolysis: every pair of consecutive precursors in the network is connected by the minimal number of enzymatic steps. Similarly, input sugars are converted into precursors by the shortest possible enzymatic paths. This suggests an optimality principle for the structure of central carbon metabolism. The present approach may be used to study other metabolic networks and to design new minimal pathways. Highlights► We study network design principles for the structure of central carbon metabolism in E. coli ► We develop an approach to find the shortest paths between metabolites using all known enzyme classes ► Consecutive precursors in central carbon metabolism are connected by minimal enzymatic paths ► Input sugars are converted into precursors in central carbon metabolism by minimal biochemical paths