AbstractA substantial fraction of the bacterial cytosol is occupied by catalysts and their substrates. While a higher volume density of catalysts and substrates might boost biochemical fluxes, the resulting molecular crowding can slow down diffusion, perturb the reactions’ Gibbs free energies, and reduce the catalytic efficiency of proteins. Due to these tradeoffs, dry mass density likely possesses an optimum that facilitates maximal cellular growth and that is interdependent on the cytosolic molecule size distribution. Here, we analyse the balanced growth of a model cell with metabolic and ribosomal reactions, accounting systematically for crowding effects on reaction kinetics. We find that changes in cytosolic density affect biochemical efficiency more strongly for ribosomal reactions than for metabolic reactions, which involve much smaller catalysts and reactants. Accordingly, optimal cytosolic density depends on cellular resource allocation into ribosomal vs. metabolic reactions. A shift in the relative contributions of these sectors to the cellular economy explains the 10% difference in the cytosolic density between E. coli bacteria growing in nutrient-rich and -poor environments. We conclude that cytosolic density variation in E. coli is consistent with an optimality principle of cellular efficiency.Significance statementThe cellular cytosol harbours diverse molecules, whose crowding slows down diffusion and perturbs the chemical equilibrium of biochemical reactions. Reaction rates thus depend not only on the reactants themselves, but also on the background density of other molecules; consequently, maximal cell growth requires an optimal density. Here, we simulate a model cell with crowding-adjusted metabolic reaction kinetics. Its cytosol accommodates two types of reactions: metabolic reactions involving small molecules, and protein production reactions involving much larger molecules. These two cellular subsystems have distinct optimal densities, and a shift in their relative contribution to the cellular biomass explains the 10% difference in the cytosolic density between E. coli bacteria growing in nutrient-rich and -poor environments.
Transferability of N-terminal mutations of pyrrolysyl-tRNA synthetase in one species to that in another species on unnatural amino acid incorporation efficiency
