Fundamental behaviors emerge from simulations of a living minimal cell

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Pages (from-to)345-360.e28
JournalCell
Volume185
Issue number2
Publication statusPublished - 20 Jan 2022
Peer-reviewedYes

External IDs

Scopus 85123004712
unpaywall 10.1016/j.cell.2021.12.025
WOS 000746168800002
ORCID /0000-0001-8901-4377/work/142232419

Keywords

Research priority areas of TU Dresden

Keywords

  • JCVI-syn3A, genetic information processing, hybrid stochastic-deterministic simulations, mRNA half-lives, metabolism, minimal cell, qPCR, time-dependent ATP costs, whole-cell kinetic model, Electrochemical proton gradient, High-throughput, Ribosome biogenesis, Stochastic simulation, Escherichia-coli, 2nd-order rate constants, Glycose phosphotransferase system, Phosphoenolpyruvate, Transient state kinetics, Rate-limiting step