Growth efficiency as a cellular objective in Eschericia coli

TL;DR

This study introduces a new cellular objective function based on growth efficiency for Escherichia coli, which better predicts cellular growth in batch cultivation than traditional methods.

Contribution

The paper proposes and validates growth efficiency as a novel cellular objective function in metabolic network analysis for E. coli.

Findings

Maximal growth efficiency occurs at a finite, substrate-dependent nutrient uptake rate.

Growth efficiency-based predictions align well with experimental data.

Growth efficiency as an objective slightly outperforms maximal growth rate in modeling accuracy.

Abstract

The identification of cellular objectives is one of the central topics in the research of microbial metabolic networks. In particular, the information about a cellular objective is needed in flux balance analysis which is a commonly used constrained-based metabolic network analysis method for the prediction of cellular phenotypes. The cellular objective may vary depending on the organism and its growth conditions. It is probable that nutritionally scarce conditions are very common in the nature and, in order to survive in those conditions, cells exhibit various highly efficient nutrient processing systems like enzymes. In this study, we explore the efficiency of a metabolic network in transformation of substrates to new biomass, and we introduce a new objective function simulating growth efficiency. We examined the properties of growth efficiency using a metabolic model for Eschericia coli. We found that the maximal growth efficiency is obtained at a finite nutrient uptake rate. The rate is substrate-dependent and it typically does not exceed 20 mmol/h/gDW. We further examined whether the maximal growth efficiency could serve as a cellular objective function in metabolic network analysis, and found that cellular growth in batch cultivation can be predicted reasonably well under this assumption. The fit to experimental data was found slightly better than with the commonly used objective function of maximal growth rate. Based on our results, we suggest that the maximal growth efficiency can be considered as a plausible optimization criterion in metabolic modeling for E. coli. In the future, it would be interesting to study growth efficiency as a cellular objective also in other cellular systems and under different cultivation conditions.