The number of active metabolic pathways is bounded by the number of cellular constraints at maximal metabolic rates
Fig 6
Under-utilization of enzymes and co-consumption can be understood with our kinetic, constrained-based approach.
a) Model simulations of the metabolic switch of L. lactis are shown (dashed lines), along with experimental data from [44]. The flux predictions for both pathways are expressed as a fraction of the total flux through both pathways. Enzyme concentrations are normalized to the concentrations at a growth rate of 0.15 and then log-scaled. The model reproduces the switch from mixed-acid to homolactic fermentation at constant enzyme concentrations, because of its consideration of enzyme kinetics. Details of this model are described in S3 Appendix. To obtain a perfect fit with the data, a larger model should be invoked, but this is beyond the scope of this paper. We emphasize that protein concentrations can remain constant while pathway usage changes. b) An example is shown of a metabolic network with EFMs that use either succinate or xylose (orange and blue circles respectively), and an EFM (green circles) that uses two carbon sources. Grey squares denote products that are essential for cell growth. The co-consumption EFM can synthesize one cell component with succinate, and the other with xylose. The reaction that connects the upper and lower parts of the network therefore becomes inessential. This leads to a possible reduction in protein costs and therefore to a growth rate advantage. We indeed measured a growth rate increase by the co-consumption of succinate and xylose, as shown in the inset in which different biological replicates are indicated with different points. Results of the other combinations that were tested can be found in S4 Appendix.