Definition
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...
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
References
Begley TP, Ealick SE, McLafferty FW. Thiamin biosynthesis: still yielding fascinating biological chemistry. Biochem Soc Trans. 2012;40:555–60.
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.
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.
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.
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.
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.
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 1980
Kronenberger T, Schettert I, Wrenger C. Targeting the vitamin biosynthesis pathways for the treatment of malaria. Future Med Chem. 2013;5:769–79.
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.
Müller S, Kappes B. Vitamin and cofactor biosynthesis pathways in Plasmodium and other apicomplexan parasites. Trends Parasitol. 2007;23:112–21.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this entry
Cite this entry
Wiesner, J., Jomaa, H. (2013). 1-Deoxy-d-Xylulose 5-Phosphate Pathway. In: Hommel, M., Kremsner, P. (eds) Encyclopedia of Malaria. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8757-9_10-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-8757-9_10-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Online ISBN: 978-1-4614-8757-9
eBook Packages: Springer Reference MedicineReference Module Medicine