1887

Abstract

Isoprenoid biosynthesis is essential for cell survival. Over 35 000 isoprenoid molecules have been identified to date in the three domains of life (bacteria, archaea and eukaryotes), and these molecules are involved in a wide variety of vital biological functions. Isoprenoids may be synthesized via one of two independent nonhomologous pathways, the classical mevalonate pathway or the alternative 2-methyl--erythritol 4-phosphate (MEP) pathway. Given that isoprenoids are indispensable, enzymes involved in their production have been investigated as potential drug targets. It has also been observed that the MEP pathway intermediate 1-hydroxy-2-methyl-2-()-butenyl 4-diphosphate (HMB-PP) can activate human Vγ9/Vδ2 T cells. Herein we review isoprenoid biosynthesis in bacterial pathogens. The role of isoprenoid biosynthesis pathways in host–pathogen interactions (virulence potential and immune stimulation) is examined. Finally, the design of antimicrobial drugs that target isoprenoid biosynthesis pathways is discussed.

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2012-06-01
2019-10-20
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References

  1. Altincicek B. , Kollas A. K. , Eberl M. , Wiesner J. , Sanderbrand S. , Hintz M. , Beck E. , Jomaa H. . ( 2001; ). LytB, a novel gene of the 2-C-methyl-d-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli . . FEBS Lett 499:, 37–40. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bailey A. M. , Mahapatra S. , Brennan P. J. , Crick D. C. . ( 2002; ). Identification, cloning, purification, and enzymatic characterization of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase. . Glycobiology 12:, 813–820. [CrossRef] [PubMed]
    [Google Scholar]
  3. Balibar C. J. , Shen X. , Tao J. . ( 2009; ). The mevalonate pathway of Staphylococcus aureus . . J Bacteriol 191:, 851–861. [CrossRef] [PubMed]
    [Google Scholar]
  4. Begley M. , Gahan C. G. , Kollas A. K. , Hintz M. , Hill C. , Jomaa H. , Eberl M. . ( 2004; ). The interplay between classical and alternative isoprenoid biosynthesis controls γδ T cell bioactivity of Listeria monocytogenes . . FEBS Lett 561:, 99–104. [CrossRef] [PubMed]
    [Google Scholar]
  5. Begley M. , Bron P. A. , Heuston S. , Casey P. G. , Englert N. , Wiesner J. , Jomaa H. , Gahan C. G. M. , Hill C. . ( 2008; ). Analysis of the isoprenoid biosynthesis pathways in Listeria monocytogenes reveals a role for the alternative 2-C-methyl-d-erythritol 4-phosphate pathway in murine infection. . Infect Immun 76:, 5392–5401. [CrossRef] [PubMed]
    [Google Scholar]
  6. Behrendt C. T. , Kunfermann A. , Illarionova V. , Matheeussen A. , Pein M. K. , Gräwert T. , Kaiser J. , Bacher A. , Eisenreich W. et al. ( 2011; ). Reverse fosmidomycin derivatives against the antimalarial drug target IspC (Dxr). . J Med Chem 54:, 6796–6802. [CrossRef] [PubMed]
    [Google Scholar]
  7. Bochar D. A. , Stauffacher C. V. , Rodwell V. W. . ( 1999; ). Sequence comparisions reveal two classes of 3-hydroxy-3-methylglutaryl coenzyme A reductase. . Mol Genet Metab 66:, 122–127.[CrossRef]
    [Google Scholar]
  8. Bonneville M. , Scotet E. . ( 2006; ). Human Vγ9Vδ2 T cells: promising new leads for immunotherapy of infections and tumors. . Curr Opin Immunol 18:, 539–546. [CrossRef] [PubMed]
    [Google Scholar]
  9. Bonneville M. , O’Brien R. L. , Born W. K. . ( 2010; ). γδ T cell effector functions: a blend of innate programming and acquired plasticity. . Nat Rev Immunol 10:, 467–478. [CrossRef] [PubMed]
    [Google Scholar]
  10. Boucher Y. , Doolittle W. F. . ( 2000; ). The role of lateral gene transfer in the evolution of isoprenoid biosynthesis pathways. . Mol Microbiol 37:, 703–716. [CrossRef] [PubMed]
    [Google Scholar]
  11. Brown A. C. , Parish T. . ( 2008; ). Dxr is essential in Mycobacterium tuberculosis and fosmidomycin resistance is due to a lack of uptake. . BMC Microbiol 8:, 78. [CrossRef] [PubMed]
    [Google Scholar]
  12. Brown A. C. , Eberl M. , Crick D. C. , Jomaa H. , Parish T. . ( 2010; ). The nonmevalonate pathway of isoprenoid biosynthesis in Mycobacterium tuberculosis is essential and transcriptionally regulated by Dxs. . J Bacteriol 192:, 2424–2433. [CrossRef] [PubMed]
    [Google Scholar]
  13. Buetow L. , Brown A. C. , Parish T. , Hunter W. N. . ( 2007; ). The structure of Mycobacteria 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase, an essential enzyme, provides a platform for drug discovery. . BMC Struct Biol 7:, 68. [CrossRef] [PubMed]
    [Google Scholar]
  14. Buhaescu I. , Izzedine H. . ( 2007; ). Mevalonate pathway: a review of clinical and therapeutical implications. . Clin Biochem 40:, 575–584. [CrossRef] [PubMed]
    [Google Scholar]
  15. Caccamo N. , Dieli F. , Wesch D. , Jomaa H. , Eberl M. . ( 2006; ). Sex-specific phenotypical and functional differences in peripheral human Vγ9/Vδ2 T cells. . J Leukoc Biol 79:, 663–666. [CrossRef] [PubMed]
    [Google Scholar]
  16. Campbell T. L. , Brown E. D. . ( 2002; ). Characterization of the depletion of 2-C-methyl-d-erythritol-2,4-cyclodiphosphate synthase in Escherichia coli and Bacillus subtilis . . J Bacteriol 184:, 5609–5618. [CrossRef] [PubMed]
    [Google Scholar]
  17. Campos N. , Rodríguez-Concepción M. , Sauret-Güeto S. , Gallego F. , Lois L. M. , Boronat A. . ( 2001a; ). Escherichia coli engineered to synthesize isopentenyl diphosphate and dimethylallyl diphosphate from mevalonate: a novel system for the genetic analysis of the 2-C-methyl-d-erythritol 4-phosphate pathway for isoprenoid biosynthesis. . Biochem J 353:, 59–67. [CrossRef] [PubMed]
    [Google Scholar]
  18. Campos N. , Rodríguez-Concepción M. , Seemann M. , Rohmer M. , Boronat A. . ( 2001b; ). Identification of gcpE as a novel gene of the 2-C-methyl-d-erythritol 4-phosphate pathway for isoprenoid biosynthesis in Escherichia coli . . FEBS Lett 488:, 170–173. [CrossRef] [PubMed]
    [Google Scholar]
  19. Catron D. M. , Lange Y. , Borensztajn J. , Sylvester M. D. , Jones B. D. , Haldar K. . ( 2004; ). Salmonella enterica serovar Typhimurium requires nonsterol precursors of the cholesterol biosynthetic pathway for intracellular proliferation. . Infect Immun 72:, 1036–1042. [CrossRef] [PubMed]
    [Google Scholar]
  20. Cornish R. M. , Roth J. R. , Poulter C. D. . ( 2006; ). Lethal mutations in the isoprenoid pathway of Salmonella enterica . . J Bacteriol 188:, 1444–1450. [CrossRef] [PubMed]
    [Google Scholar]
  21. Crane C. M. , Hirsch A. K. , Alphey M. S. , Sgraja T. , Lauw S. , Illarionova V. , Rohdich F. , Eisenreich W. , Hunter W. N. et al. ( 2008; ). Synthesis and characterization of cytidine derivatives that inhibit the kinase IspE of the non-mevalonate pathway for isoprenoid biosynthesis. . ChemMedChem 3:, 91–101. [CrossRef] [PubMed]
    [Google Scholar]
  22. Davey M. S. , Lin C. Y. , Roberts G. W. , Heuston S. , Brown A. C. , Chess J. A. , Toleman M. A. , Gahan C. G. M. , Hill C. et al. ( 2011; ). Human neutrophil clearance of bacterial pathogens triggers anti-microbial γδ T cell responses in early infection. . PLoS Pathog 7:, e1002040. [CrossRef] [PubMed]
    [Google Scholar]
  23. Durrant J. D. , Cao R. , Gorfe A. A. , Zhu W. , Li J. , Sankovsky A. , Oldfield E. , McCammon J. A. . ( 2011; ). Non-bisphosphonate inhibitors of isoprenoid biosynthesis identified via computer-aided drug design. . Chem Biol Drug Des 78:, 323–332. [CrossRef] [PubMed]
    [Google Scholar]
  24. Eberl M. , Altincicek B. , Kollas A. K. , Sanderbrand S. , Bahr U. , Reichenberg A. , Beck E. , Foster D. , Wiesner J. et al. ( 2002; ). Accumulation of a potent γδ T-cell stimulator after deletion of the lytB gene in Escherichia coli . . Immunol 106:, 200–211. [CrossRef]
    [Google Scholar]
  25. Eberl M. , Hintz M. , Reichenberg A. , Kollas A. K. , Wiesner J. , Jomaa H. . ( 2003; ). Microbial isoprenoid biosynthesis and human γδ T cell activation. . FEBS Lett 544:, 4–10. [CrossRef] [PubMed]
    [Google Scholar]
  26. Eberl M. , Roberts G. W. , Meuter S. , Williams J. D. , Topley N. , Moser B. . ( 2009; ). A rapid crosstalk of human γδ T cells and monocytes drives the acute inflammation in bacterial infections. . PLoS Pathog 5:, e1000308. [CrossRef] [PubMed]
    [Google Scholar]
  27. Eoh H. , Brennan P. J. , Crick D. C. . ( 2009; ). The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target. . Tuberculosis (Edinb) 89:, 1–11. [CrossRef] [PubMed]
    [Google Scholar]
  28. Ershov Y. V. . ( 2007; ). 2-C-Methylerythritol phosphate pathway of isoprenoid biosynthesis as a target in identifying new antibiotics, herbicides, and immunomodulators: a review. 2007. . Appl Biochem Microbiol 43:, 115–138. [CrossRef]
    [Google Scholar]
  29. Eskra L. , Canavessi A. , Carey M. , Splitter G. . ( 2001; ). Brucella abortus genes identified following constitutive growth and macrophage infection. . Infect Immun 69:, 7736–7742. [CrossRef] [PubMed]
    [Google Scholar]
  30. Freiberg C. , Wieland B. , Spaltmann F. , Ehlert K. , Brötz H. , Labischinski H. . ( 2001; ). Identification of novel essential Escherichia coli genes conserved among pathogenic bacteria. . J Mol Microbiol Biotechnol 3:, 483–489.[PubMed]
    [Google Scholar]
  31. Gabrielsen M. , Rohdich F. , Eisenreich W. , Gräwert T. , Hecht S. , Bacher A. , Hunter W. N. . ( 2004; ). Biosynthesis of isoprenoids: a bifunctional IspDF enzyme from Campylobacter jejuni . . Eur J Biochem 271:, 3028–3035. [CrossRef] [PubMed]
    [Google Scholar]
  32. Garner M. J. , Hayward R. D. , Koronakis V. . ( 2002; ). The Salmonella pathogenicity island 1 secretion system directs cellular cholesterol redistribution during mammalian cell entry and intracellular trafficking. . Cell Microbiol 4:, 153–165. [CrossRef] [PubMed]
    [Google Scholar]
  33. Gill S. R. , Pop M. , Deboy R. T. , Eckburg P. B. , Turnbaugh P. J. , Samuel B. S. , Gordon J. I. , Relman D. A. , Fraser-Liggett C. M. , Nelson K. E. . ( 2006; ). Metagenomic analysis of the human distal gut microbiome. . Science 312:, 1355–1359. [CrossRef] [PubMed]
    [Google Scholar]
  34. Gophna U. , Thompson J. R. , Boucher Y. , Doolittle W. F. . ( 2006; ). Complex histories of genes encoding 3-hydroxy-3-methylglutaryl-CoenzymeA reductase. . Mol Biol Evol 23:, 168–178. [CrossRef] [PubMed]
    [Google Scholar]
  35. Gräwert T. , Span I. , Eisenreich W. , Rohdich F. , Eppinger J. , Bacher A. , Groll M. . ( 2010; ). Probing the reaction mechanism of IspH protein by x-ray structure analysis. . Proc Natl Acad Sci U S A 107:, 1077–1081. [CrossRef] [PubMed]
    [Google Scholar]
  36. Grieshaber N. A. , Fischer E. R. , Mead D. J. , Dooley C. A. , Hackstadt T. . ( 2004; ). Chlamydial histone-DNA interactions are disrupted by a metabolite in the methylerythritol phosphate pathway of isoprenoid biosynthesis. . Proc Natl Acad Sci U S A 101:, 7451–7456. [CrossRef] [PubMed]
    [Google Scholar]
  37. Hammond R. K. , White D. C. . ( 1970; ). Carotenoid formation by Staphylococcus aureus . . J Bacteriol 103:, 191–198.[PubMed]
    [Google Scholar]
  38. Hasan S. , Daugelat S. , Rao P. S. , Schreiber M. . ( 2006; ). Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis . . PLOS Comput Biol 2:, e61. [CrossRef] [PubMed]
    [Google Scholar]
  39. Hecht S. , Eisenreich W. , Adam P. , Amslinger S. , Kis K. , Bacher A. , Arigoni D. , Rohdich F. . ( 2001; ). Studies on the nonmevalonate pathway to terpenes: the role of the GcpE (IspG) protein. . Proc Natl Acad Sci U S A 98:, 14837–14842. [CrossRef] [PubMed]
    [Google Scholar]
  40. Herz S. , Wungsintaweekul J. , Schuhr C. A. , Hecht S. , Lüttgen H. , Sagner S. , Fellermeier M. , Eisenreich W. , Zenk M. H. et al. ( 2000; ). Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate to 2C-methyl-d-erythritol 2,4-cyclodiphosphate. . Proc Natl Acad Sci U S A 97:, 2486–2490. [CrossRef] [PubMed]
    [Google Scholar]
  41. Hill R. E. , Himmeldirk K. , Kennedy I. A. , Pauloski R. M. , Sayer B. G. , Wolf E. , Spenser I. D. . ( 1996; ). The biogenetic anatomy of vitamin B6. A 13C NMR investigation of the biosynthesis of pyridoxol in Escherichia coli . . J Biol Chem 271:, 30426–30435. [CrossRef] [PubMed]
    [Google Scholar]
  42. Hintz M. , Reichenberg A. , Altincicek B. , Bahr U. , Gschwind R. M. , Kollas A. K. , Beck E. , Wiesner J. , Eberl M. , Jomaa H. . ( 2001; ). Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human γδ T cells in Escherichia coli . . FEBS Lett 509:, 317–322. [CrossRef] [PubMed]
    [Google Scholar]
  43. Hirsch A. K. , Alphey M. S. , Lauw S. , Seet M. , Barandun L. , Eisenreich W. , Rohdich F. , Hunter W. N. , Bacher A. , Diederich F. . ( 2008; ). Inhibitors of the kinase IspE: structure–activity relationships and co-crystal structure analysis. . Org Biomol Chem 6:, 2719–2730. [CrossRef] [PubMed]
    [Google Scholar]
  44. Hunter W. N. . ( 2007; ). The non-mevalonate pathway of isoprenoid precursor biosynthesis. . J Biol Chem 282:, 21573–21577. [CrossRef] [PubMed]
    [Google Scholar]
  45. Illarionova V. , Kaiser J. , Ostrozhenkova E. , Bacher A. , Fischer M. , Eisenreich W. , Rohdich F. . ( 2006; ). Nonmevalonate terpene biosynthesis enzymes as antiinfective drug targets: substrate synthesis and high-throughput screening methods. . J Org Chem 71:, 8824–8834. [CrossRef]
    [Google Scholar]
  46. Jahnke W. , Rondeau J. M. , Cotesta S. , Marzinzik A. , Pellé X. , Geiser M. , Strauss A. , Götte M. , Bitsch F. et al. ( 2010; ). Allosteric non-bisphosphonate FPPS inhibitors identified by fragment-based discovery. . Nat Chem Biol 6:, 660–666. [CrossRef] [PubMed]
    [Google Scholar]
  47. Jawaid S. , Seidle H. , Zhou W. , Abdirahman H. , Abadeer M. , Hix J. H. , van Hoek M. L. , Couch R. D. . ( 2009; ). Kinetic characterization and phosphoregulation of the Francisella tularensis 1-deoxy-d-xylulose 5-phosphate reductoisomerase (MEP synthase). . PLoS ONE 4:, e8288. [CrossRef] [PubMed]
    [Google Scholar]
  48. Jomaa H. , Feurle J. , Lühs K. , Kunzmann V. , Tony H. P. , Herderich M. , Wilhelm M. . ( 1999a; ). Vγ9/Vδ2 T cell activation induced by bacterial low molecular mass compounds depends on the 1-deoxy-d-xylulose 5-phosphate pathway of isoprenoid biosynthesis. . FEMS Immunol Med Microbiol 25:, 371–378. [CrossRef]
    [Google Scholar]
  49. Jomaa H. , Wiesner J. , Sanderbrand S. , Altincicek B. , Weidemeyer C. , Hintz M. , Türbachova I. , Eberl M. , Zeidler J. et al. ( 1999b; ). Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. . Science 285:, 1573–1576. [CrossRef] [PubMed]
    [Google Scholar]
  50. Kuntz L. , Tritsch D. , Grosdemange-Billiard C. , Hemmerlin A. , Willem A. , Bach T. J. , Rohmer M. . ( 2005; ). Isoprenoid biosynthesis as a target for antibacterial and antiparasitic drugs: phosphonohydroxamic acids as inhibitors of deoxyxylulose phosphate reducto-isomerase. . Biochem J 386:, 127–135. [CrossRef] [PubMed]
    [Google Scholar]
  51. Kurz T. , Schlüter K. , Kaula U. , Bergmann B. , Walter R. D. , Geffken D. . ( 2006; ). Synthesis and antimalarial activity of chain substituted pivaloyloxymethyl ester analogues of Fosmidomycin and FR900098. . Bioorg Med Chem 14:, 5121–5135. [CrossRef] [PubMed]
    [Google Scholar]
  52. Kuzuyama T. , Takahashi S. , Takagi M. , Seto H. . ( 2000; ). Characterization of 1-deoxy-d-xylulose 5-phosphate reductoisomerase, an enzyme involved in isopentenyl diphosphate biosynthesis, and identification of its catalytic amino acid residues. . J Biol Chem 275:, 19928–19932. [CrossRef] [PubMed]
    [Google Scholar]
  53. Lai Y. C. , Peng H. L. , Chang H. Y. . ( 2001; ). Identification of genes induced in vivo during Klebsiella pneumoniae CG43 infection. . Infect Immun 69:, 7140–7145. [CrossRef] [PubMed]
    [Google Scholar]
  54. Lange B. M. , Rujan T. , Martin W. , Croteau R. . ( 2000; ). Isoprenoid biosynthesis: the evolution of two ancient and distinct pathways across genomes. . Proc Natl Acad Sci U S A 97:, 13172–13177. [CrossRef] [PubMed]
    [Google Scholar]
  55. Laupitz R. , Hecht S. , Amslinger S. , Zepeck F. , Kaiser J. , Richter G. , Schramek N. , Steinbacher S. , Huber R. et al. ( 2004; ). Biochemical characterization of Bacillus subtilis type II isopentenyl diphosphate isomerase, and phylogenetic distribution of isoprenoid biosynthesis pathways. . Eur J Biochem 271:, 2658–2669. [CrossRef] [PubMed]
    [Google Scholar]
  56. Lell B. , Ruangweerayut R. , Wiesner J. , Missinou M. A. , Schindler A. , Baranek T. , Hintz M. , Hutchinson D. , Jomaa H. , Kremsner P. G. . ( 2003; ). Fosmidomycin, a novel chemotherapeutic agent for malaria. . Antimicrob Agents Chemother 47:, 735–738. [CrossRef] [PubMed]
    [Google Scholar]
  57. Lombard J. , Moreira D. . ( 2011; ). Origins and early evolution of the mevalonate pathway of isoprenoid biosynthesis in the three domains of life. . Mol Biol Evol 28:, 87–99. [CrossRef] [PubMed]
    [Google Scholar]
  58. Matsumi R. , Atomi H. , Driessen A. J. , van der Oost J. . ( 2011; ). Isoprenoid biosynthesis in Archaea – biochemical and evolutionary implications. . Res Microbiol 162:, 39–52. [CrossRef] [PubMed]
    [Google Scholar]
  59. McAteer S. , Coulson A. , McLennan N. , Masters M. . ( 2001; ). The lytB gene of Escherichia coli is essential and specifies a product needed for isoprenoid biosynthesis. . J Bacteriol 183:, 7403–7407. [CrossRef] [PubMed]
    [Google Scholar]
  60. Miallau L. , Alphey M. S. , Kemp L. E. , Leonard G. A. , McSweeney S. M. , Hecht S. , Bacher A. , Eisenreich W. , Rohdich F. , Hunter W. N. . ( 2003; ). Biosynthesis of isoprenoids: crystal structure of 4-diphosphocytidyl-2C-methyl-d-erythritol kinase. . Proc Natl Acad Sci U S A 100:, 9173–9178. [CrossRef] [PubMed]
    [Google Scholar]
  61. Morita C. T. , Jin C. , Sarikonda G. , Wang H. . ( 2007; ). Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vγ2Vδ2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. . Immunol Rev 215:, 59–76. [CrossRef] [PubMed]
    [Google Scholar]
  62. Obiol-Pardo C. , Rubio-Martinez J. , Imperial S. . ( 2011; ). The methylerythritol phosphate (MEP) pathway for isoprenoid biosynthesis as a target for the development of new drugs against tuberculosis. . Curr Med Chem 18:, 1325–1338. [CrossRef] [PubMed]
    [Google Scholar]
  63. Ostrovsky D. , Diomina G. , Lysak E. , Matveeva E. , Ogrel O. , Trutko S. . ( 1998; ). Effect of oxidative stress on the biosynthesis of 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate and isoprenoids by several bacterial strains. . Arch Microbiol 171:, 69–72. [CrossRef] [PubMed]
    [Google Scholar]
  64. Pérez-Gil J. , Bergua M. , Boronat A. , Imperial S. . ( 2010; ). Cloning and functional characterization of an enzyme from Helicobacter pylori that catalyzes two steps of the methylerythritol phosphate pathway for isoprenoid biosynthesis. . Biochim Biophys Acta 1800:, 919–928. [CrossRef] [PubMed]
    [Google Scholar]
  65. Pethe K. , Swenson D. L. , Alonso S. , Anderson J. , Wang C. , Russell D. G. . ( 2004; ). Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation. . Proc Natl Acad Sci U S A 101:, 13642–13647. [CrossRef] [PubMed]
    [Google Scholar]
  66. Puan K. J. , Wang H. , Dairi T. , Kuzuyama T. , Morita C. T. . ( 2005; ). fldA is an essential gene required in the 2-C-methyl-d-erythritol 4-phosphate pathway for isoprenoid biosynthesis. . FEBS Lett 579:, 3802–3806. [CrossRef] [PubMed]
    [Google Scholar]
  67. Putra S. R. , Disch A. , Bravo J.-M. , Rohmer M. . ( 1998; ). Distribution of mevalonate and glyceraldehyde 3-phosphate/pyruvate routes for isoprenoid biosynthesis in some Gram-negative bacteria and mycobacteria. . FEMS Microbiol Lett 164:, 169–175. [CrossRef] [PubMed]
    [Google Scholar]
  68. Ramsden N. L. , Buetow L. , Dawson A. , Kemp L. A. , Ulaganathan V. , Brenk R. , Klebe G. , Hunter W. N. . ( 2009; ). A structure-based approach to ligand discovery for 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy. . J Med Chem 52:, 2531–2542. [CrossRef] [PubMed]
    [Google Scholar]
  69. Reichenberg A. , Hintz M. , Kletschek Y. , Kuhl T. , Haug C. , Engel R. , Moll J. , Ostrovsky D. N. , Jomaa H. , Eberl M. . ( 2003; ). Replacing the pyrophosphate group of HMB-PP by a diphosphonate function abrogates Its potential to activate human γδ T cells but does not lead to competitive antagonism. . Bioorg Med Chem Lett 13:, 1257–1260. [CrossRef] [PubMed]
    [Google Scholar]
  70. Rekittke I. , Wiesner J. , Röhrich R. , Demmer U. , Warkentin E. , Xu W. , Troschke K. , Hintz M. , No J. H. et al. ( 2008; ). Structure of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, the terminal enzyme of the non-mevalonate pathway. . J Am Chem Soc 130:, 17206–17207. [CrossRef] [PubMed]
    [Google Scholar]
  71. Richard S. B. , Bowman M. E. , Kwiatkowski W. , Kang I. , Chow C. , Lillo A. M. , Cane D. E. , Noel J. P. . ( 2001; ). Structure of 4-diphosphate-2-C-methylerythritol synthase involved in mevalonate-independent isoprenoid biosynthesis. . Struct Biol Nature 8:, 641–648. [CrossRef]
    [Google Scholar]
  72. Rodríguez-Concepción M. , Campos N. , María Lois L. , Maldonado C. , Hoeffler J. F. , Grosdemange-Billiard C. , Rohmer M. , Boronat A. . ( 2000; ). Genetic evidence of branching in the isoprenoid pathway for the production of isopentenyl diphosphate and dimethylallyl diphosphate in Escherichia coli . . FEBS Lett 473:, 328–332. [CrossRef] [PubMed]
    [Google Scholar]
  73. Rohdich F. , Wungsintaweekul J. , Fellermeier M. , Sagner S. , Herz S. , Kis K. , Eisenreich W. , Bacher A. , Zenk M. H. . ( 1999; ). Cytidine 5′-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol. . Proc Natl Acad Sci U S A 96:, 11758–11763. [CrossRef] [PubMed]
    [Google Scholar]
  74. Rohdich F. , Kis K. , Bacher A. , Eisenreich W. . ( 2001; ). The non-mevalonate pathway of isoprenoids: genes, enzymes and intermediates. . Curr Opin Chem Biol 5:, 535–540. [CrossRef] [PubMed]
    [Google Scholar]
  75. Rohdich F. , Zepeck F. , Adam P. , Hecht S. , Kaiser J. , Laupitz R. , Gräwert T. , Amslinger S. , Eisenreich W. et al. ( 2003a; ). The deoxyxylulose phosphate pathway of isoprenoid biosynthesis: studies on the mechanisms of the reactions catalyzed by IspG and IspH protein. . Proc Natl Acad Sci U S A 100:, 1586–1591. [CrossRef] [PubMed]
    [Google Scholar]
  76. Rohdich F. , Hecht S. , Bacher A. , Eisenreich W. . ( 2003b; ). Deoxyxylulose phosphate pathway of isoprenoid biosynthesis. Discovery and function of ispDEFGH genes and their cognate enzymes. . Pure Appl Chem 75:, 393–405. [CrossRef]
    [Google Scholar]
  77. Rohdich F. , Bacher A. , Eisenreich W. . ( 2005; ). Isoprenoid biosynthetic pathways as anti-infective drug targets. . Biochem Soc Trans 33:, 785–791. [CrossRef] [PubMed]
    [Google Scholar]
  78. Sangari F. J. , Pérez-Gil J. , Carretero-Paulet L. , García-Lobo J. M. , Rodríguez-Concepción M. . ( 2010; ). A new family of enzymes catalyzing the first committed step of the methylerythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in bacteria. . Proc Natl Acad Sci U S A 107:, 14081–14086. [CrossRef] [PubMed]
    [Google Scholar]
  79. Schauer K. , Geginat G. , Liang C. , Goebel W. , Dandekar T. , Fuchs T. M. . ( 2010; ). Deciphering the intracellular metabolism of Listeria monocytogenes by mutant screening and modelling. . BMC Genomics 11:, 573. [CrossRef] [PubMed]
    [Google Scholar]
  80. Sgraja T. , Alphey M. S. , Ghilagaber S. , Marquez R. , Robertson M. N. , Hemmings J. L. , Lauw S. , Rohdich F. , Bacher A. et al. ( 2008; ). Characterization of Aquifex aeolicus 4-diphosphocytidyl-2C-methyl-d-erythritol kinase – ligand recognition in a template for antimicrobial drug discovery. . FEBS J 275:, 2779–2794. [CrossRef] [PubMed]
    [Google Scholar]
  81. Shi W. , Feng J. , Zhang M. , Lai X. , Xu S. , Zhang X. , Wang H. . ( 2007; ). Biosynthesis of isoprenoids: characterization of a functionally active recombinant 2-C-methyl-d-erythritol 4-phosphate cytidyltransferase (IspD) from Mycobacterium tuberculosis H37Rv. . J Biochem Mol Biol 40:, 911–920. [CrossRef] [PubMed]
    [Google Scholar]
  82. Shigemori H. , Komaki H. , Yazawa K. , Mikami Y. , Nemoto A. , Tanaka Y. , Kobayashi J. . ( 1999; ). Biosynthesis of diterpenoid moiety of brasilicardin A via non-mevalonate pathway in Nocardia brasiliensis. . Tetrahedron Lett 40:, 4353–4354.[CrossRef]
    [Google Scholar]
  83. Shin S. J. , Wu C. W. , Steinberg H. , Talaat A. M. . ( 2006; ). Identification of novel virulence determinants in Mycobacterium paratuberculosis by screening a library of insertional mutants. . Infect Immun 74:, 3825–3833. [CrossRef] [PubMed]
    [Google Scholar]
  84. Singh N. , Chevé G. , Avery M. A. , McCurdy C. R. . ( 2007; ). 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 13:, 1161–1177. [CrossRef] [PubMed]
    [Google Scholar]
  85. Steinbacher S. , Kaiser J. , Eisenreich W. , Huber R. , Bacher A. , Rohdich F. . ( 2003; ). Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-d-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development. . J Biol Chem 278:, 18401–18407. [CrossRef] [PubMed]
    [Google Scholar]
  86. Takagi M. , Kaneda K. , Shimizu T. , Hayakawa Y. , Seto H. , Kuzuyama T. . ( 2004; ). Bacillus subtilis ypgA gene is fni, a nonessential gene encoding type 2 isopentenyl diphosphate isomerase. . Biosci Biotechnol Biochem 68:, 132–137. [CrossRef] [PubMed]
    [Google Scholar]
  87. Testa C. A. , Brown M. J. . ( 2003; ). The methylerythritol phosphate pathway and its significance as a novel drug target. . Curr Pharm Biotechnol 4:, 248–259. [CrossRef] [PubMed]
    [Google Scholar]
  88. Theivagt A. E. , Amanti E. N. , Beresford N. J. , Tabernero L. , Friesen J. A. . ( 2006; ). Characterization of an HMG-CoA reductase from Listeria monocytogenes that exhibts dual coenzyme specificity. . Biochem 45:, 14397–14406. [CrossRef]
    [Google Scholar]
  89. Tsang A. , Seidle H. , Jawaid S. , Zhou W. , Smith C. , Couch R. D. . ( 2011; ). Francisella tularensis 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase: kinetic characterization and phosphoregulation. . PLoS ONE 6:, e20884. [CrossRef] [PubMed]
    [Google Scholar]
  90. Voynova N. E. , Rios S. E. , Miziorko H. M. . ( 2004; ). Staphylococcus aureus mevalonate kinase: isolation and characterization of an enzyme of the isoprenoid biosynthetic pathway. . J Bacteriol 186:, 61–67. [CrossRef] [PubMed]
    [Google Scholar]
  91. Wang K. , Wang W. , No J. H. , Zhang Y. , Zhang Y. , Oldfield E. . ( 2010; ). Inhibition of the Fe4S4-cluster-containing protein IspH (LytB): electron paramagnetic resonance, metallacycles, and mechanisms. . J Am Chem Soc 132:, 6719–6727. [CrossRef] [PubMed]
    [Google Scholar]
  92. Wang H. , Sarikonda G. , Puan K. J. , Tanaka Y. , Feng J. , Giner J. L. , Cao R. , Mönkkönen J. , Oldfield E. , Morita C. T. . ( 2011a; ). Indirect stimulation of human Vγ2Vδ2 T cells through alterations in isoprenoid metabolism. . J Immunol 187:, 5099–5113. [CrossRef]
    [Google Scholar]
  93. Wang W. , Li J. , Wang K. , Smirnova T. I. , Oldfield E. . ( 2011b; ). Pyridine inhibitor binding to the 4Fe-4S protein A. aeolicus IspH (LytB): a HYSCORE investigation. . J Am Chem Soc 133:, 6525–6528. [CrossRef] [PubMed]
    [Google Scholar]
  94. Wilding E. I. , Kim D.-Y. , Bryant A. P. , Gwynn M. N. , Lunsford R. D. , McDevitt D. , Myers J. E. Jr , Rosenberg M. , Sylvester D. et al. ( 2000a; ). Essentiality, expression, and characterization of the class II 3-hydroxy-3-methylglutaryl coenzyme A reductase of Staphylococcus aureus . . J Bacteriol 182:, 5147–5152. [CrossRef] [PubMed]
    [Google Scholar]
  95. Wilding E. I. , Brown J. R. , Bryant A. P. , Chalker A. F. , Holmes D. J. , Ingraham K. A. , Iordanescu S. , So C. Y. , Rosenberg M. , Gwynn M. N. . ( 2000b; ). Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in Gram-positive cocci. . J Bacteriol 182:, 4319–4327. [CrossRef] [PubMed]
    [Google Scholar]
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