Fundamental behaviors emerge from simulations of a living minimal cell

We present a whole-cell fully dynamical kinetic model (WCM) of JCVI-syn3A, a minimal cell with a reduced genome of 493 genes that has retained few regulatory proteins or small RNAs. Cryo-electron tomograms provide the cell geometry and ribosome distributions. Time-dependent behaviors of concentrations and reaction fluxes from stochastic-deterministic simulations over a cell cycle reveal how the cell balances demands of its metabolism, genetic information processes, and growth, and offer insight into the principles of life for this minimal cell. The energy economy of each process including active transport of amino acids, nucleosides, and ions is analyzed. WCM reveals how emergent imbalances lead to slowdowns in the rates of transcription and translation. Integration of experimental data is critical in building a kinetic model from which emerges a genome-wide distribution of mRNA half-lives, multiple DNA replication events that can be compared to qPCR results, and the experimentally observed doubling behavior.

Automated summary

This study presents a whole-cell fully dynamical kinetic model (WCM) of JCVI-syn3A, a minimal cell, to investigate its behavior and provide insights into the principles of life for this microorganism. The model reveals the strategies employed by the cell to balance its metabolism, genetic processes, and growth, and analyzes the energy economy of various processes. Integration of experimental data in building the kinetic model allows for the prediction of mRNA half-lives, comparison with qPCR results, and observation of doubling behavior.