(475b) A Metabolomics-Based Analysis of Central Carbon Metabolism in 14 Yeast Species

Metabolic processes within a cell produce the energy and small molecule building blocks necessary for all cellular functions, and central carbon metabolism - the key metabolic module governing energy sources - is the cornerstone of these processes. Despite this key role, we understand surprisingly little about the function and evolution of central carbon metabolism on a systems scale. In this project we perform a comparative experimental and computational study of the function, regulation, and evolution of central carbon metabolism in fourteen Ascomycota fungi spanning 300 million years of evolution. We systematically measure intracellular metabolite concentrations under glucose depletion and other environmental perturbations. We integrate these metabolite profiles with expression profiles collected in our lab under the same conditions for a multi-scale analysis of how these metabolic responses have evolved across the phylogeny. We identify functional metabolic modules of co-varying metabolites and genes in each species, and we use a novel computational approach to identify orthologous modules across species and reconstruct their evolution. This reconstruction predicts conserved functional entities and major evolutionary changes in metabolic function and regulation. This innovative comparative metabolomic approach provides insights into the function and evolution of distinct metabolic strategies and establishes a new systems-level approach for the study of metabolic systems.