Modeling the cell cycle of the minimal bacterial cell JCVI-syn3A

The minimal bacterium JCVI-syn3A, with only 492 genes, provides a unique opportunity for whole-cell computational modeling. We have a whole-cell model of metabolism and genetic information processing based on gene essentiality and proteomics studies (Breuer et al., eLife 2019). This is a kinetic model, as opposed to flux balance analysis of the essential metabolism which only predicts steady state behavior, and our simulations are hybrid stochastic-deterministic. To achieve a complete cell cycle in the whole-cell computational model of JCVI-syn3A it is necessary to model its growth and subsequent division mediated by Z-ring assembly. Our whole-cell kinetic model predicts a membrane growth rate based on the synthesis and incorporation of lipids and membrane proteins. The well-stirred kinetic model recapitulates the experimentally measured growth rates, with the cell surface area and initial protein counts doubling on average in 97 minutes. Cryo-electron tomograms give the location of the cell's ribosomes for a small (~200 nm radius) and large cell (~250 nm radius). From this experimental data, we simulate growth by updating membrane size and ribosome positions and translocating membrane proteins.