Figure 5

Comparison of strategies by the metabolic model and the integrated metabolic and regulatory model. The OptKnock deletion strategies in Figure 3 were re-analyzed using the integrated metabolic and regulatory model, where their corresponding gene deletions were the same but the maximum growth rate and ethanol production were re-calculated with the integrated model. (A-B) The ethanol yields and growth rates for most of the OptKnock strains (blue triangles) were predicted to be significantly lower by the integrated model than the those predicted by the metabolic model alone (Figure 3B and 3C) due to transcriptional regulatory constraints. Also shown are strain designed using OptORF (green circles) when transcriptional regulation is included (gene overexpression was not allowed such that K₂ = 0). (C) For each OptKnock strategy, we identified the minimal number of genes (whose expression is repressed by the transcriptional regulation) that were needed to be overexpressed to achieve the same ethanol yield as predicted by the unregulated metabolic model (Figure 3B and 3C).