Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis pathway of Naegleria fowleri
Fig 1
Sterol metabolic network in N. fowleri.
The pathway is reconstituted based on the metabolites observed in the untreated N. fowleri (shown in bold) and treated with the CYP51 (shown in green), SMT (in blue) and ERG2 (in dark red) inhibitors. Metabolites not observed in the wild-type N. fowleri are depicted in thin lines. The cholesterol arm of the pathway is highlighted by the yellow-green background, the ergosterol arm is highlighted by the blue background. Enclosed in frame are potential SMT substrates. Enzymes interrogated in these studies are labeled in colors corresponding to the accumulating metabolites. Numbering of atoms in sterol molecule is adapted from Nes and Venkatramesh, 1994.[41] Sterol labelling is as in Table 1. ERG enzyme nomenclature is according to the convention for S. cerevisiae.