Encyclopedia of Malaria

Living Edition
| Editors: Peter G. Kremsner, Sanjeev Krishna

1-Deoxy-d-Xylulose 5-Phosphate Pathway

  • Jochen Wiesner
  • Hassan Jomaa
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-8757-9_10-1



The 1-deoxy- d-xylulose 5-phosphate (DXP) pathway is a metabolic pathway for the conversion of pyruvate and d-glyceraldehyde 3-phosphate (G3P) into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) by seven enzymatic reaction steps (all intermediates and enzymes together with their common abbreviations are listed in Tables 1 and 2, respectively). In all organisms studied so far, IPP and DMAPP are the precursor molecules for the synthesis of a class of biomolecules known as isoprenoids (or terpenoids). In P. falciparum, the DXP pathway is the only metabolic route leading to IPP and DMAPP. The enzymes of the DXP pathway of P. falciparum are localized inside the apicoplast. The DXP pathway is absent in humans who use the well-known mevalonate pathway instead (Fig. 1). Through the mevalonate pathway, three molecules of acetyl CoA...


Antimalarial Activity Mevalonate Pathway Parasite Growth Dimethylallyl Diphosphate Isoprenoid Precursor 
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  1. Begley TP, Ealick SE, McLafferty FW. Thiamin biosynthesis: still yielding fascinating biological chemistry. Biochem Soc Trans. 2012;40:555–60.PubMedCentralPubMedCrossRefGoogle Scholar
  2. Clastre M, Goubard A, Prel A, Mincheva Z, Viaud-Massuart MC, Bout D, Rideau M, Velge-Roussel F, Laurent F. The methylerythritol phosphate pathway for isoprenoid biosynthesis in coccidia: presence and sensitivity to fosmidomycin. Exp Parasitol. 2007;116:375–84.PubMedCrossRefGoogle Scholar
  3. Eberl M, Hintz M, Reichenberg A, Kollas AK, Wiesner J, Jomaa H. Microbial isoprenoid biosynthesis and human gammadelta T cell activation. FEBS Lett. 2003;544:4–10.PubMedCrossRefGoogle Scholar
  4. Fitzpatrick TB, Amrhein N, Kappes B, Macheroux P, Tews I, Raschle T. Two independent routes of de novo vitamin B6 biosynthesis: not that different after all. Biochem J. 2007;407:1–13.PubMedCrossRefGoogle Scholar
  5. Goble JL, Johnson H, de Ridder J, Stephens LL, Louw A, Blatch GL, Boshoff A. The druggable antimalarial target PfDXR: overproduction strategies and kinetic characterization. Protein Pept Lett. 2013;20:115–24.PubMedCrossRefGoogle Scholar
  6. Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Türbachova I, Eberl M, Zeidler J, Lichtenthaler HK, Soldati D, Beck E. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science. 1999;285:1573–6.PubMedCrossRefGoogle Scholar
  7. Kamiya T, Hashimoto M, Hemmi K, Takeno H (1980) Hydroxyaminohydrocarbon-phosphonic acids. Fujisawa Pharmaceutical Co. Ltd. U.S. Patent Application No. 4,206,156, 3 June 1980Google Scholar
  8. Kronenberger T, Schettert I, Wrenger C. Targeting the vitamin biosynthesis pathways for the treatment of malaria. Future Med Chem. 2013;5:769–79.PubMedCrossRefGoogle Scholar
  9. Lanaspa M, Moraleda C, Machevo S, González R, Serrano B, Macete E, Cisteró P, Mayor A, Hutchinson D, Kremsner PG, Alonso P, Menéndez C, Bassat Q. Inadequate efficacy of a new formulation of fosmidomycin-clindamycin combination in Mozambican children less than three years old with uncomplicated Plasmodium falciparum malaria. Antimicrob Agents Chemother. 2012;56:2923–8.PubMedCentralPubMedCrossRefGoogle Scholar
  10. Müller S, Kappes B. Vitamin and cofactor biosynthesis pathways in Plasmodium and other apicomplexan parasites. Trends Parasitol. 2007;23:112–21.PubMedCentralPubMedCrossRefGoogle Scholar
  11. Riganti C, Massaia M, Davey MS, Eberl M. Human γδ T-cell responses in infection and immunotherapy: common mechanisms, common mediators? Eur J Immunol. 2012;42:1668–76.PubMedCrossRefGoogle Scholar
  12. Rodríguez-Concepción M, Boronat A. Isoprenoid biosynthesis in prokaryotic organisms. In: Bach TJ, Gershenzon J, Rohmer M, editors. New concepts in plant and microbial isoprenoid research. New York: Springer; 2013. p. 1–16.Google Scholar
  13. Rodríguez-Concepción M, Campos N, Ferrer A, Boronat A. Biosynthesis of isoprenoid precursors in Arabidopsis. In: Bach TJ, Gershenzon J, Rohmer M, editors. New concepts in plant and microbial isoprenoid research. New York: Springer; 2013. p. 439–56.Google Scholar
  14. Rohdich F, Eisenreich W, Wungsintaweekul J, Hecht S, Schuhr CA, Bacher A. Biosynthesis of terpenoids. 2C-Methyl-d-erythritol 2,4-cyclodiphosphate synthase (IspF) from Plasmodium falciparum. Eur J Biochem. 2001;268:3190–7.PubMedCrossRefGoogle Scholar
  15. Rohmer M. From molecular fossils of bacterial hopanoids to the formation of isoprene units: discovery and elucidation of the methylerythritol phosphate pathway. Lipids. 2008;43:1095–107.PubMedCrossRefGoogle Scholar
  16. Röhrich RC, Englert N, Troschke K, Reichenberg A, Hintz M, Seeber F, Balconi E, Aliverti A, Zanetti G, Köhler U, Pfeiffer M, Beck E, Jomaa H, Wiesner J. Reconstitution of an apicoplast-localized electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum. FEBS Lett. 2005;579:6433–8.PubMedCrossRefGoogle Scholar
  17. Singh N, Chevé G, Avery MA, McCurdy CR. Targeting the methyl erythritol phosphate (MEP) pathway for novel antimalarial, antibacterial and herbicidal drug discovery: inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) enzyme. Curr Pharm Des. 2007;13:1161–77.PubMedCrossRefGoogle Scholar
  18. Umeda T, Tanaka N, Kusakabe Y, Nakanishi M, Kitade Y, Nakamura KT. Molecular basis of fosmidomycin’s action on the human malaria parasite Plasmodium falciparum. Sci Rep. 2011;1:9.PubMedCentralPubMedCrossRefGoogle Scholar
  19. Wiesner J, Reichenberg A, Heinrich S, Schlitzer M, Jomaa H. The plastid-like organelle of apicomplexan parasites as drug target. Curr Pharm Des. 2008;14:855–71.PubMedCrossRefGoogle Scholar
  20. Wiesner J, Reichenberg A, Hintz M, Ortmann R, Schlitzer M, Van Calenbergh S, Borrmann S, Lell B, Kremsner PG, Hutchinson D, Jomaa H. Fosmidomycin as an antimalarial agent. In: Bach TJ, Gershenzon J, Rohmer M, editors. New concepts in plant and microbial isoprenoid research. New York: Springer; 2013. p. 119–37.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Bioresources Project GroupFraunhofer Institute for Molecular Biology and Applied Ecology IMEGießenGermany
  2. 2.Institute for Clinical Immunology and Transfusion MedicineJustus-Liebig University GießenGießenGermany