Details

Autor(en) / Beteiligte

• Thornburg, Zane R.
• Bianchi, David M.
• Brier, Troy A.
• Gilbert, Benjamin R.
• Earnest, Tyler M.
• Melo, Marcelo C.R.
• Safronova, Nataliya
• Sáenz, James P.
• Cook, András T.
• Wise, Kim S.
• Hutchison, Clyde A.
• Smith, Hamilton O.
• Glass, John I.
• Luthey-Schulten, Zaida

Titel

Fundamental behaviors emerge from simulations of a living minimal cell

Ist Teil von

• Cell, 2022-01, Vol.185 (2), p.345-360.e28

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •3D spatial resolution of a fully dynamical whole-cell kinetic model•Detailed single-reaction, single-cell accounting of time-dependent ATP costs•Genome-wide mRNA half-lives emerge from length-dependent kinetics and diffusion•Connections among metabolism, genetic information, and cell growth are revealed A kinetic model for a minimal bacterial cell offers quantitative insight into how the cell balances processes from metabolism to gene expression to growth.