Motivation: Protein allocation determines activity of cellular
pathways and affects growth across all organisms. Therefore, a variety
of experimental and machine learning approaches has been developed to
quantify and predict protein abundances, respectively. Yet, despite
advances in protein quantification, it remains challenging to predict
condition-specific allocation of enzymes in metabolic networks.
Results: Here we propose a family of constrained-based
approaches, termed PARROT, to predict enzyme allocations based on the
principle of minimizing the enzyme allocation adjustment using protein
constrained metabolic models. To this end, PARROT variants model the
minimization of enzyme reallocation using four different (combinations
of) distance functions. We demonstrate that the PARROT variant that
minimizes the Manhattan distance of enzyme allocations outperforms
existing approaches based on the parsimonious distribution of fluxes or
enzymes for both Escherichia coli and Saccharomyces
cerevisiae. Further, we show that the combined minimization of flux and
enzyme allocation adjustment leads to poor and inconsistent predictions.
Together, our findings indicate that minimization of resource rather
than flux redistribution is a governing principle determining
steady-state pathway activity for microorganism grown in suboptimal
conditions.
Availability and implementation: The implementation of PARROT
can be found in the GitHub repository:
https://github.com/mauricioamf/PARROT