Fundamental Escherichia coli biochemical pathways for biomass and energy production: identification of reactions

Cells grow by oxidizing nutrients using a complex network of biochemical reactions. During this process new biological material is produced along with energy used for maintaining cellular organization. Because the metabolic network is highly branched, these tasks can be accomplished using a wide variety of unique reaction sequences. However, evolutionary pressures under carbon-limited growth conditions likely select organisms that utilize highly efficient pathways. Using elementary-mode analysis, we demonstrate that the metabolism of the bacterium Escherichia coli contains four unique pathways that most efficiently convert glucose and oxygen into new cells and maintenance energy under any level of oxygen limitation. Observed regulatory patterns and experimental findings suggest growing cells use these highly efficient pathways. It is predicted that five knockout mutations generate a strain that supports growth using only the most efficient reaction sequence. The analysis approach should be generally useful for predicting metabolic capabilities and efficient network designs based on only genomic information.