Figure 4.

Prediction of switching or shifting of optimal metabolic strategies. (A) The two alternative metabolically efficient (MetEf) and catalytically efficient (CatEf) pathways that replace the ‘Metabolic pathway' in Figure 3A. The CatEf pathway is metabolically inefficient because it not only generates less Precursor per Substrate molecule, but also requires less protein (or equivalently, has higher k_cat) than the MetEf pathway to generate a similar flux of Precursor. The graph on the right shows the optimal relative flux through each of these pathways as a function of the extracellular substrate concentration. (B) A different configuration of metabolism, namely one in which an energy intermediate (ATP) is produced with different efficiencies in the alternative pathways. The ATP is used to activate an intermediate to a precursor. Also here the CatEf pathway has a higher k_cat than the MetEf pathway. In contrast to the configuration in panel A, a mixed strategy is optimal at a range of substrate concentrations in this configuration (see the text for an explanation). (C, D) Experimental data of shifts in metabolism of L. lactis (Thomas et al, 1979) (C) and S. cerevisiae (van Hoek et al, 1998) (D). L. lactis shifts from the metabolically efficient mixed-acid fermentation at low growth rates to lactic acid fermentation at high growth rates, whereas S. cerevisiae shifts from respiratory metabolism to partial ethanol fermentation.