Energy costs of coupled metabolic and genetic information processes in a living minimal bacterial cell: Life at the edge

We recently published a 4D whole cell model (4DWCM) of a minimal bacterial cell (with only 493 genes) growing in a rich medium. Time-dependent behaviors of concentrations and reaction fluxes from hybrid stochastic-deterministic simulations over a cell cycle reveal how the cell balances demands of its metabolism, genetic information processes, and growth. The ATP energy economy of each process including active transport of amino acids, nucleosides, and ions is analyzed. Emergent imbalances in availability of nucleotides and amino acids can lead to slowdowns in the rates of transcription and translation. Integration of experimental data is critical in building a 4DWCM from which emerges a genome-wide distribution of mRNA half-lives, multiple DNA replication events that are compared to qPCR measurements, and the experimentally observed doubling behavior