The synthesis of cellular isoprenoids is an essential process, utilizing two alternative pathways (that have distinct evolutionary origins and are separated phylogenetically) to form the common intermediate metabolites isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Most eukaryotes utilize the mevalonate (MVA) pathway (see our Lanosterol biosynthesis pathway page for more details), but phyla such as Plasmodium, that have acquired a plastid organelle, generate isoprenoids using the non-mevalonate or methylerythritol phosphate (MEP) pathway [2]. The complete pathway for P. falciparum is available at www.wikipathways.org and is shown below. Enzymes of the MEP pathway represent promising therapeutic targets for antimalarial drug development because the pathway is present in the Plasmodium parasite but not in the human host [1].

In the malaria parasite, the products of the MEP pathway are metabolized further by the bifunctional farnesyl/geranylgeranyl diphosphate synthase (PfFPPS/GGPPS) enzyme. Farnesyl diphosphate synthase (FPPS) catalyzes the coupling of IPP and DMAPP and is a key metabolic branch point in isoprenoid synthesis [3].

1. Imlay LS, Armstrong CM, Masters MC, Li T, Price KE, Edwards RL, Mann KM, Li LX, Stallings CL, Berry NG et al.. (2015) Plasmodium IspD (2-C-Methyl-D-erythritol 4-Phosphate Cytidyltransferase), an Essential and Druggable Antimalarial Target. ACS Infect Dis, 1 (4): 157-167. [PMID:26783558]

2. Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Türbachova I, Eberl M, Zeidler J, Lichtenthaler HK et al.. (1999) Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science, 285 (5433): 1573-6. [PMID:10477522]

3. Jordão FM, Gabriel HB, Alves JM, Angeli CB, Bifano TD, Breda A, de Azevedo MF, Basso LA, Wunderlich G, Kimura EA et al.. (2013) Cloning and characterization of bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase from Plasmodium falciparum. Malar J, 12: 184. [PMID:23734739]