Mathematical modeling of proteome constraints within metabolism

Genome-scale metabolic models (GEMs) are widely used to predict phenotypes with the aid of constraint-based modeling. In order to improve the predictive power of these models, there have been many efforts on imposing biological constraints, among which proteome constraints are of particular interest. Here we describe the concept of proteome constraints and review proteome-constrained GEMs, as well as their advantages and applications. In addition, we discuss a key issue in the field, i.e., low coverage of enzyme-specific turnover rates, and subsequently provide a few solutions to solve it. We end with a discussion on the trade-off between model complexity and capability.