Fig. 1

Overview of our systems approach to predict the impact of metabolism on acetylation. Using a genome-scale metabolic model, we first simulate the effect of different nutrient environments and gene deletions on protein acetylation. We then simulate the impact of the cellular metabolic state on vulnerability to compounds that disrupt acetylation (protein deacetylase inhibitors). We subsequently predict variation in susceptibility to these drugs between different cell types depending on their metabolic state. Abbreviations—A, B are metabolites and Enz1, Enz2, and Enz3 are metabolic enzymes