Modeling the minimal cell: Integration of experiments, theory, and simulations

JCVI-syn3A, a robust minimal cell with a 543 kbp genome and 493 genes, provides a versatile
platform to study the principles of life (Breuer et al. eLife 2019). Using the vast amount of
experimental information available on its precursor, Mycoplasma mycoides capri, we assembled
a near-complete essential metabolic network with 98% of enzymatic reactions supported by
annotation or experiment. This coherent model of the minimal metabolism along with the maps
of all its protein-coding genes and proteomics data point toward specific open questions
regarding the minimal genome, which still contains many genes of generic or completely unclear
function. The identification of 30 essential genes with unclear function will motivate the search
for new biological mechanisms beyond metabolism. Finally, stochastic dynamics of the
combined genetic information processes of DNA replication, transcription, translation and
ribosome biogenesis clarifies quantitatively demands on the metabolic network over the twohour
cell cycle.