Fig. 5
Model-predicted metabolism of untreated Dd2, PA21A092-treated Dd2A211V, and KAE609-treated Dd2A211V. A Hierarchical clustering analysis of non-zero metabolic fluxes in untreated wildtypes (WT) and mutants treated with pyrazoleamide compound PA21A092 (MT + PA21A092) and spiroindolone compound KAE609 (MT + KAE609). The cluster analysis revealed metabolic reactions having substantially different flux in the presence of PA21A092, but not in the absence of drugs or in the presence of KAE609, annotated using 1 (vertical stripes) and 2 (horizontal stripes).\( {\widehat{\text{v}}}^{\text{t}}\) denotes temporal flux of an enzyme after normalization by its median value in the untreated WT parasites. B) Metabolic fluxes in wildtypes (WT; black), PA21A092-treated mutants (MT; blue), and KAE609-treated mutants (MT; green) along two reduced dimensions. The red ellipse contains metabolic reactions, primarily, from PA21A092-treated mutants. C Metabolic pathways associated with the metabolic reactions contained in the red ellipse (B), Cluster 1 (A), and Cluster 2 (A). AA amino acid reactions, Carb carbohydrate reactions, Lip lipid reactions, Nuc nucleotides, Tr transport reactions; Vit cofactors and vitamin reactions