Constrain and conquer

Abstract

Optimal allocation of available cellular resources is central for microorganisms to strive and outcompete individuals of the same and other microbial species. Allocation of resources mainly manifests as production of proteins required to sustain growth, and thus shapes the metabolic strategies microbes undertake. In different conditions, different metabolic strategies are superior to others (sustain fastest growth per unit protein), and will be adopted as a result of optimal resource allocation. We have been using computational large-scale, fine-grained resource allocation models to characterize resource allocation strategies in three model microorganisms: Escherichia coli, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. We find that different metabolic strategies are selected in a condition-dependent manner based on both their efficacy per protein and allocation of respective proteins in different cellular compartments. Moreover, we observe that perturbations of these optimal strategies (e.g. forced expression of unneeded protein) come at the cost of decreased growth rate, consistent with existing body of experimental data. Finally, we use these models to test biological hypotheses and thus argue that resource allocation models can be successfully used to identify the metabolic strategies which govern microbial growth.