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.
Fundamental behaviors emerge from simulations of a living minimal cell.
通过对最小活细胞的模拟,可以发现基本行为
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作者: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 3rd, Smith Hamilton O, Glass John I, Luthey-Schulten Zaida
| 期刊: | Cell | 影响因子: | 42.500 |
| 时间: | 2022 | 起止号: | 2022 Jan 20; 185(2):345-360 |
| doi: | 10.1016/j.cell.2021.12.025 | 研究方向: | 细胞生物学 |
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