Growth efficiency as a cellular objective in Eschericia coli

13 The identification of cellular objectives is one of the central topics in the research of 14 microbial metabolic networks. In particular, the information about a cellular objective is 15 needed in flux balance analysis which is a commonly used constrained-based metabolic 16 network analysis method for the prediction of cellular phenotypes. The cellular objective 17 may vary depending on the organism and its growth conditions. It is probable that 18 nutritionally scarce conditions are very common in the nature and, in order to survive in 19 those conditions, cells exhibit various highly efficient nutrient processing systems like 20 enzymes. In this study, we explore the efficiency of a metabolic network in 21 transformation of substrates to new biomass, and we introduce a new objective function 22 simulating growth efficiency. 23 24 We examined the properties of growth efficiency using a metabolic model for Eschericia 25 coli. We found that the maximal growth efficiency is obtained at a finite nutrient uptake 26 rate. The rate is substrate-dependent and it typically does not exceed 20 mmol/h/gDW. 27 We further examined whether the maximal growth efficiency could serve as a cellular 28 objective function in metabolic network analysis, and found that cellular growth in batch 29 cultivation can be predicted reasonably well under this assumption. The fit to 30 experimental data was found slightly better than with the commonly used objective 31 function of maximal growth rate. 32 33 Based on our results, we suggest that the maximal growth efficiency can be considered as 34 a plausible optimization criterion in metabolic modeling for E. coli. In the future, it 35 3 would be interesting to study growth efficiency as a cellular objective also in other 36 cellular systems and under different cultivation conditions. 37 38