Isoprenoid precursor biosynthesis in Pf apicoplasts (WP2918)

Plasmodium falciparum

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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.

Authors

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

Activity

last edited

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Cited In

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Organisms

Plasmodium falciparum

Communities

Annotations

Disease Ontology

Plasmodium falciparum malaria

Pathway Ontology

malaria pathway

Participants

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
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

References

  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