Assembly of Macromolecular Complexes in the Whole-Cell Model of a Minimal Cell

Macromolecular complexes
in the genetically minimized bacterium,
JCVI-syn3A, support gene expression (RNA polymerase, ribosome, degradosome),
metabolism (ABC transporters, ATP synthase), and chromosome dynamics.
In this work, we further incorporate the assembly of 21 unique macromolecular
complexes into the existing whole-cell kinetic model of Syn3A. The
synthesis and translocation of protein subunits in membrane complexes
occur through distinct pathways. A range of 2D association rates for
membrane complexes were considered to guarantee a high yield of assembly,
given the existing time scales of gene expression. By alleviation
of the undesired kinetically trapped intermediates in ATP synthase
assembly, the efficiency was improved. The assembly of RNA polymerase,
ribosome, and degradosome influences the speed and efficiency of protein
synthesis. Collectively, this model predicted time-dependent cellular
behaviors consistent with experiments. A machine learning analysis
of the time-dependent metabolomics and metabolic fluxes highlighted
the effect of introducing a complex assembly into our whole-cell model.