Isoprenoid precursor biosynthesis in Pf apicoplasts (WP2918)

Plasmodium falciparum

This pathway shows a apicoplast of the Plasmodium falciparum that infected a human cell. The human glycolysis provides the apicoplast with nutrients for its isoprenoid precursor biosynthesis. This pathway is being investigated for targets for malaria drug leads and drugs.


Egon Willighagen , Alex Pico , Kristina Hanspers , Denise Slenter , and Eric Weitz


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Plasmodium falciparum



Disease Ontology

Plasmodium falciparum malaria

Pathway Ontology

malaria pathway


Label Type Compact URI Comment
DMAPP Metabolite pubchem.compound:647 Minor product.
DOXP Metabolite chebi:57792 1-deoxy-D-xylulose 5-phosphate
pyruvate Metabolite chebi:15361
Phosphoenolpyruvic acid Metabolite hmdb:HMDB0000263
fosmidomycin Metabolite chemspider:555
MMV008138 Metabolite pubchem.compound:987146
Glycerone-P Metabolite chebi:16108
CDP-MEP Metabolite pubchem.compound:443200 4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate
D-Glyceraldehyde 3-phosphate Metabolite hmdb:HMDB0001112
CDP-ME Metabolite chebi:16578 4-Diphosphocytidyl-2-C-methylerythritol
IPP Metabolite pubchem.compound:1195
MEP Metabolite chebi:58262 2C-methyl-D-erythritol 4-phosphate
Phosphoenolpyruvic acid Metabolite hmdb:HMDB0000263
Glycerone-P Metabolite chebi:16108
MEPC Metabolite pubchem.compound:126747 4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate
IspD GeneProduct ensembl:PFA0340w PF3D7_0106900; PFA0340w; .7.7.60
IspC GeneProduct ncbigene:812223
IspF GeneProduct uniprot:A0A1D3RDA4
IspE GeneProduct uniprot:A0A1D3U940
Triose-P/Pi translocator GeneProduct ncbigene:812861
DXS GeneProduct ncbigene:813741
PEP/Pi translocator GeneProduct ncbigene:813115
IspH GeneProduct interpro:IPR003451
IspG GeneProduct uniprot:Q9BJX5


  1. Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children. Borrmann S, Adegnika AA, Matsiegui PB, Issifou S, Schindler A, Mawili-Mboumba DP, et al. J Infect Dis. 2004 Mar 1;189(5):901–8. PubMed Europe PMC Scholia
  2. Fosmidomycin plus clindamycin for treatment of pediatric patients aged 1 to 14 years with Plasmodium falciparum malaria. Borrmann S, Lundgren I, Oyakhirome S, Impouma B, Matsiegui PB, Adegnika AA, et al. Antimicrob Agents Chemother. 2006 Aug;50(8):2713–8. PubMed Europe PMC Scholia
  3. The non-mevalonate pathway of isoprenoid precursor biosynthesis. Hunter WN. J Biol Chem. 2007 Jul 27;282(30):21573–7. PubMed Europe PMC Scholia
  4. Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria. Ruangweerayut R, Looareesuwan S, Hutchinson D, Chauemung A, Banmairuroi V, Na-Bangchang K. Malar J. 2008 Oct 31;7:225. PubMed Europe PMC Scholia
  5. Isoprenoid metabolism as a therapeutic target in gram-negative pathogens. Wiemer AJ, Hsiao CHC, Wiemer DF. Curr Top Med Chem. 2010;10(18):1858–71. PubMed Europe PMC Scholia
  6. Isoprenoid precursor biosynthesis offers potential targets for drug discovery against diseases caused by apicomplexan parasites. Hunter WN. Curr Top Med Chem. 2011;11(16):2048–59. PubMed Europe PMC Scholia
  7. Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum. Yeh E, DeRisi JL. PLoS Biol. 2011 Aug;9(8):e1001138. PubMed Europe PMC Scholia
  8. A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitor targeting MEP isoprenoid precursor biosynthesis. Wu W, Herrera Z, Ebert D, Baska K, Cho SH, DeRisi JL, et al. Antimicrob Agents Chemother. 2015 Jan;59(1):356–64. PubMed Europe PMC Scholia
  9. Determination of the active stereoisomer of the MEP pathway-targeting antimalarial agent MMV008138, and initial structure-activity studies. Yao ZK, Krai PM, Merino EF, Simpson ME, Slebodnick C, Cassera MB, et al. Bioorg Med Chem Lett. 2015 Apr 1;25(7):1515–9. PubMed Europe PMC Scholia