Targeting DXP synthase in human pathogens: Enzyme inhibition and antimicrobial activity of butylacetylphosphonate

Journal of Antibiotics

Volumn 67, Issue 1, 2014, Pages 77-83

  Smith, Jessica M ^a   Warrington, Nicole V ^b   Vierling, Ryan J ^a   Kuhn, Misty L ^c   Anderson, Wayne F ^c   Koppisch, Andrew T ^b   Freel Meyers, Caren L ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NORTHERN ARIZONA UNIVERSITY   (United States)

^c NORTHWESTERN UNIVERSITY   (United States)

Author keywords

DXP synthase; Isoprenoid biosynthesis; Selective inhibitor; Thiamin diphosphate

Indexed keywords

1 DEOXY D XYLULOSE 5 PHOSPHATE SYNTHASE; ANTIINFECTIVE AGENT; BACTERIAL ENZYME; BUTYLACETYLPHOSPHONATE; PHOSPHONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; ARTICLE; BACILLUS ANTHRACIS; BACTERIAL STRAIN; BACTERIUM ISOLATION; CONTROLLED STUDY; DRUG INHIBITION; DRUG SELECTIVITY; ENZYME INHIBITION; ESCHERICHIA COLI; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN TARGETING; SALMONELLA ENTERICA; YERSINIA PESTIS;

ANTI-BACTERIAL AGENTS; DRUG RESISTANCE, BACTERIAL; DRUG SYNERGISM; ENZYME INHIBITORS; GRAM-NEGATIVE BACTERIA; GRAM-POSITIVE BACTERIA; HUMANS; MOLECULAR TARGETED THERAPY; ORGANOPHOSPHONATES; TRANSFERASES;

EID: 84893044653     PISSN: 00218820     EISSN: 18811469     Source Type: Journal    
DOI: 10.1038/ja.2013.105     Document Type: Article

References (54)

1. Arigoni, D. et al. Terpenoid biosynthesis from 1-deoxy-D-xylulose in higher plants by intramolecular skeletal rearrangement. Proc. Natl Acad. Sci. USA 94, 10600-10605 (1997
2. Rohmer, M., Knani, M., Simonin, P., Sutter, B. & Sahm, H. Isoprenoid biosynthesis in bacteria: A novel pathway for the early steps leading to isopentenyl diphosphate. Biochem. J. 15, 517-524 (1993
3. Walsh, C. T. Antibiotics: Actions, Origins, Resistance (ASM Press, Washington, DC, USA, 2003
4. Sprenger, G. A. et al. Identification of a thiamin-dependent synthase in Escherichia coli required for the formation of the 1-deoxy-D-xylulose 5-phosphate precursor to isoprenoids, thiamin, and pyridoxol. Proc. Natl Acad. Sci. USA 94, 12857-12862 (1997
5. Lois, L. M. et al. Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1-deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis. Proc. Natl Acad. Sci. USA 95, 2105-2110 (1998
6. Kuzuyama, T., Takagi, M., Takahashi, S. & Seto, H. Cloning and characterization of 1-deoxy-D-xylulose 5-phosphate synthase from Streptomyces sp. strain CL190, which uses both the mevalonate and nonmevalonate pathways for isopentenyl diphosphate biosynthesis. J. Bacteriol. 15, 891-897 (2000
7. Hahn, F. M. et al. 1-Deoxy-D-xylulose 5-phosphate synthase, the gene product of open reading frame (ORF) 2816 and ORF 2895 in Rhodobacter capsulatus. J. Bacteriol. 183, 1-11 (2001
8. Bailey, A. M., Mahapatra, S., Brennan, P. J. & Crick, D. C. Identification, cloning, purification, and enzymatic characterization of Mycobacterium tuberculosis 1-deoxy-Dxylulose 5-phosphate synthase. Glycobiology 12, 813-820 (2002
9. Lee, J., Oh, D. & Kim, S. Cloning and characterization of the dxs gene, encoding 1-deoxy-D-xylulose 5-phosphate synthase from Agrobacterium tumefaciens, and its overexpression in Agrobacterium tumefaciens. J. Biotechnol. 128, 555-566 (2007
10. O'Brien, T. A., Kluger, R., Pike, D. C. & Gennis, R. B. Phosphonate analogues of pyruvate. Probes of substrate binding to pyruvate oxidase and other thiamin pyrophosphate-dependent decarboxylases. Biochim. Biophys. Acta 613, 10-17 (1980
11. Brammer, L. A., Smith, J. M. & Meyers, C. F. 1-Deoxy-D-xylulose 5-phosphate synthase catalyzes a novel random sequential mechanism. J. Biol. Chem. 42, 36522-36531 (2011
12. Altincicek, B. et al. Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase: An approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa. FEMS Microbiol. Lett. 190, 329-333 (2000
13. Mao, J. et al. Structure-Activity relationships of compounds targeting Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate synthase. Bioorg. Med. Chem. Lett. 18, 5320-5323 (2008
14. Matsue, Y. et al. The herbicide ketoclomazone inhibits 1-deoxy-D-xylulose 5-phosphate synthase in the 2-C-methyl-D-erythritol 4-phosphate pathway and shows antibacterial activity against Haemophilus influenzae. J. Antibiot. 63, 583-588 (2010
15. Xiang, S., Usunow, G., Lange, G., Busch, M. & Tong, L. Crystal structure of 1-deoxy-Dxylulose 5-phosphate synthase, a crucial enzyme for isoprenoids biosynthesis. J. Biol. Chem. 282, 2676-2682 (2007
16. Morris, F., Vierling, R., Boucher, L., Bosch, J. & Freel Meyers, C. L. DXP synthasecatalyzed C-N bond formation: Nitroso substrate specificity studies guide selective inhibitor design. ChemBioChem 14, 1309-1315 (2013
17. Eubanks, L. M. & Poulter, C. D. Rhodobacter capsulatus 1-deoxy-D-xylulose 5-phosphate synthase: Steady-state kinetics and substrate binding. Biochemistry 42, 1140-1149 (2003
18. Patel, H., Nemeria, N. S., Brammer, L. A., Meyers, C. F. & Jordan, F. Observation of thiamin-bound intermediates and microscopic rate constants for their interconversion on 1-deoxy-D-xylulose 5-phosphate synthase: 600-fold rate acceleration of pyruvate decarboxylation by D-glyceraldehyde-3-phosphate. J. Am. Chem. Soc. 44, 18374-18379 (2013
19. Smith, J. M., Vierling, R. J. & Meyers, C. F. Selective inhibition of E. coli 1-deoxy-Dxylulose-5-phosphate synthase by acetylphosphonates. Med. Chem. Commun. 3, 65-67 (2012
20. Kluger, R. & Pike, D. C. Active site generated analogs of reactive intermediates in enzymic reactions. Potent inhibition of pyruvate dehydrogenase by a phosphonate analog of pyruvate. J. Am. Chem. Soc. 13, 4504-4506 (1977
21. Gish, G., Smyth, T. & Kluger, R. Thiamin diphosphate catalysis. Mechanistic divergence as a probe of substrate activation of pyruvate decarboxylase. J. Am. Chem. Soc. 18, 6230-6234 (1988
22. Bearne, S. L. & Kluger, R. Phosphoenol acetylphosphonates: Substrate analogues as inhibitors of phosphoenolpyruvate enzymes. Bioorg. Chem. 20, 135-147 (1992
23. Arjunan, P. et al. A thiamin-bound, pre-decarboxylation reaction intermediate analogue in the pyruvate dehydrogenase E1 subunit induces large scale disorder-to-order transformations in the enzyme and reveals novel structural features in the covalently bound adduct. J. Biol. Chem. 281, 15296-15303 (2006
24. Nemeria, N. S., Korotchkina, L. G., Chakraborty, S., Patel, M. S. & Jordan, F. Acetylphosphinate is the most potent mechanism-based substrate-like inhibitor of both the human and Escherichia coli pyruvate dehydrogenase components of the pyruvate dehydrogenase complex. Bioorg. Chem. 34, 362-379 (2006
25. Kale, S., Arjunan, P., Furey, W. & Jordan, F. A dynamic loop at the active center of the Escherichia coli pyruvate dehydrogenase complex E1 component modulates substrate utilization and chemical communication with the E2 component. J. Biol. Chem. 282, 28106-28116 (2007
26. Flournoy, D. S. & Frey, P. A. Inactivation of the pyruvate dehydrogenase complex of Escherichia coli by fluoropyruvate. Biochemistry 25, 9594-9602 (1989
27. Nemeria, N. et al. The 10,40-iminopyrimidine tautomer of thiamin diphosphate is poised for catalysis in asymmetric active centers on enzymes. Proc. Natl Acad. Sci. USA 104, 78-82 (2007
28. Brammer, L. A. & Meyers, C. F. Revealing substrate promiscuity of 1-deoxy-D-xylulose 5-phosphate synthase. Org. Lett. 20, 4748-4751 (2009
29. Dieckman, L., Gu, M., Stols, L., Donnelly, M. I. & Collart, F. R. High throughput methods for gene cloning and expression. Protein Expr. Purif. 25, 1-7 (2002
30. Stols, L. et al. A new vector for high-throughput, ligation-independent cloning encoding a tobacco etch virus protease cleavage site. Protein Expr. Purif. 25, 8-15 (2002
31. Moody, J. in Clinical Microbiology Procedures Handbook Vol. 2 (ed. Isenberg, H. D.) 5.12.1-5.12.23 (American Society for Microbiology, Washington, DC, USA, 2004
32. Pillai, S. K., Moellering, R. C. & Eliopoulos, G.M. Antimicrobial Combinations. Antibiotics in Laboratory Medicine (ed Lorian, V.) (Lippincott Williams & Wilkins, 2005
33. Kuzuyama, T., Takagi, M., Takahashi, S. & Seto, H. Cloning and characterization of 1-deoxy-D-xylulose 5-phosphate synthase from Streptomyces sp. Strain CL190, which uses both the mevalonate and nonmevalonate pathways for isopentenyl diphosphate biosynthesis. J. Bacteriol. 182, 891-897 (2000
34. Venkateswaran, P. S. & Wu, H. C. Isolation and characterization of a phosphonomycinresistant mutant of Escherichia coli K-12. J. Bacteriol. 110, 935-944 (1972
35. McKenney, E. S. et al. Lipophilic prodrugs of FR900098 are antimicrobial against Francisella novicida in vivo and in vitro and show GlpT independent efficacy. PLoS One 10, 38167 (2012
36. Brown, A. C., Eberl, M., Crick, D. C., Jomaa, H. & Parish, T. The nonmevalonate pathway of isoprenoid biosynthesis in Mycobacterium tuberculosis is essential and transcriptionally regulated by Dxs. J. Bacteriol. 192, 2424-2433 (2010
37. Sakamoto, Y., Furukawa, S., Ogihara, H. & Yamasaki, M. Fosmidomycin resistance in adenylate cyclase deficient (cya) mutants of Escherichia coli. Biosci. Biotechnol. Biochem. 67, 2030-2033 (2003
38. Giner, J., Giner, J., Jaun, B. & Arigoni, D. Biosynthesis of isoprenoids in Escherichia coli: The fate of the 3-H and 4-H atoms of 1-deoxy-D-xylulose. Chem. Commun. 1857-1858 (1998
39. Wungsintaweekul, J. et al. Phosphorylation of 1-deoxy-D-xylulose by D-xylulokinase of Escherichia coli. Eur. J. Biochem. 268, 310-316 (2001
40. Hill, R. E. et al. The biogenetic anatomy of vitamin B6. A 13C NMR investigation of the biosynthesis of pyridoxolin in E. coli. J. Biol. Chem. 271, 30426-30435 (1996
41. Campbell, T. L. & Brown, E. D. Characterization of the depletion of 2-C-methyl-Derythritol-2,4-cyclodiphosphate synthase in Escherichia coli and Bacillus subtilis. J. Bacteriol. 184, 5609-5618 (2002
42. Okuhara, M. et al. Studies on new phosphonic acid antibiotics. J. Antibiot. 33, 13-17 (1980
43. Kuroda, Y. et al. Studies on new phosphonic acid antibiotics: 4. Structure determination of FR-33289, FR-31564 and FR-32863. J. Antibiot. 33, 29-35 (1980
44. Kuzuyama, T., Shimizu, T., Takahashi, S. & Seto, H. Fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in the nonmevalonate pathway for terpenoid biosynthesis. Tetrahedron Lett. 39, 7913-7916 (1998
45. Leon, A. et al. Isoprenoid biosynthesis as a drug target: Bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin. J. Med. Chem. 25, 7331-7341 (2006
46. Neu, H. & Kamimura, T. Synergy of fosmidomycin (FR-31564) and otherantimicrobial agents. Antimicrob. Agents Chemother. 22, 560-563 (1982
47. Dumelin, C., Chen, Y., Leconte, A., Chen, Y. & Liu, D. Discovery and biological characterization of geranylated RNA in bacteria. Nat. Chem. Biol. 11, 913-919 (2012
48. Kalan, L. & Wright, G. D. Antibiotic adjuvants: Multicomponent anti-infective strategies. Expert Rev. Mol. Med. 13, e5 (2011
49. Circello, B., Miller, C., Lee, J., van der Donk, W. & Metcalf, W. The antibioticdehydrophos is converted to a toxic pyruvate analog by peptide bond cleavage in Salmonella enterica. Antimicrob. Agents Chemother. 55, 3357-3362 (2011
50. Bitok, J. & Meyers, C. F. 2C-methyl-D-erythritol 4-phosphate enhances and sustains cyclodiphosphate synthase IspF activity. ACS Chem. Biol. 7, 1702-1710 (2012
51. Zhu, W. et al. Antibacterial drug leads targeting isoprenoid biosynthesis. Proc. Natl Acad. Sci. USA 110, 123-128 (2013
52. Walsh, C. T. & Wencewicz, T. A. Prospects for new antibiotics: A molecule-centered perspective. J. Antibiot. doi:10.1038/ja.2013.49 (in press
53. Erb, T. et al. A RubisCO-like protein links SAM metabolism with isoprenoid biosynthesis. Nat. Chem. Biol. 8, 926-932 (2012
54. Perez-Gil, J. et al. Mutations in Escherichia coli aceE and ribB genes allow survival of strains defective in the first step of the isoprenoid biosynthesis pathway. PLoS One 8, e43775 (2012 Diseases Diseases