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Inhibitors of imidazoleglycerolphosphate dehydratase as herbicides

Published online by Cambridge University Press:  12 June 2017

Daisaku Ohta ,
Ichiro Mori  and
Eric Ward
Daisaku Ohta*
Affiliation:
International Research Laboratories, Ciba-Geigy Japan Ltd., 10-66 Miyukicho Takarazuka 665, Japan
Ichiro Mori
Affiliation:
International Research Laboratories, Ciba-Geigy Japan Ltd., Japan
Eric Ward
Affiliation:
Agricultural Biotechnology, Ciba-Geigy Corp., Reserach Triangle Park, NC 27709
*
daisaku.ohta@jpta.MHS.CIBA.COM.
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Abstract

An enzyme-directed approach has led to finding specific inhibitors of imidazoleglycerolphosphate dehydratase (IGPD), which catalyzes a dehydration reaction of imidazoleglycerol phosphate (IGP) to form imidazoleacetol phosphate in the biosynthesis of histidine. These newly synthesized IGPD inhibitors showed wide-spectrum, postemergence herbicidal activity at application rates ranging from 0.05 to 2 kg ai ha−1. IGPD from wheat germ was purified to apparent homogeneity and characterized, and IGPD cDNAs were isolated from Arabidopsis and wheat cDNA libraries. Both the purified plant enzyme and the recombinant enzymes, which have been prepared by expressing the isolated IGPD cDNAs in the baculovirus/insect cell system, were used for establishment of an in vitro enzyme assay for inhibitor evaluation. Enzyme inhibitors were designed and synthesized by considering the structure of the substrate, IGP, and the inhibition activities were enhanced by a systematic structure—activity relationship study in vitro. Three triazole phosphonates, IRL 1695, IRL 1803, and IRL 1856, inhibited the reaction of the enzyme with Ki values of 40 ± 6.5 nM, 10 ± 1.6 nM, and 8.5 ± 1.4 nM, respectively, and were highly cytotoxic to cultured plant cells. Plant cell growth inhibition was completely reversed only by l-histidine, proving that the cytotoxicity was primarily caused by the inhibition of histidine biosynthesis. These new IGPD inhibitors have demonstrated that the specific inhibition of plant IGPD is lethal to plants. Further, treatment of Arabidopsis with IRL 1803 affected gene expression of eight enzymes involved in the biosynthesis of aromatic amino acids, histidine, lysine, and purines. These effects were reversed by the addition of l-histidine, indicating that the changes in gene expression were caused by the inhibition of l-histidine biosynthesis. These results indicate that higher plants, like microorganisms, are capable of cross-pathway metabolic regulation.

Keywords

IRL 1695, [3-Hydroxy-3-(4.H.-[1,2,4]triazole-3-yl)-propyl]-phosphonic acidIRL 1803, [3-Hydroxy-3-(4.H.-[1,2,4]triazole-3-yl)-cyclohexyl]-phosphonic acidIRL 1856, [3-Hydroxy-3-(4.H.-[1,2,4]triazole-3-yl)-butyl]-phosphonic acidArabidopsis, Arabidopsis thalianawheat, Triticum aestivum L.ARBTHenzyme inhibitorhistidine biosynthesis
Type
Symposium
Information
Weed Science , Volume 45 , Issue 5 , October 1997 , pp. 610 - 620
Copyright
Copyright © 1997 by the Weed Science Society of America 

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References

Literature Cited

Alifano, P., Fani, R., Lio, P., Lazcano, A., Bazzicalupo, M., Carlomagno, M. S., Bruni, C. B. 1996. Histidine biosynthetic pathway and genes: structure, regulation and evolution. Microbiol. Rev. 60: 44–69.CrossRefGoogle ScholarPubMed
Ames, B. N. 1957. The biosynthesis of histidine: d-erythro-imidazoleglycerol phosphate dehydratase. J. Biol Chem. 228: 131–143.Google Scholar
Ames, B. N. and Mitchell, H. K. 1955. The biosynthesis of histidine: imidazoleglycerol phosphate, imidazoleacetol phosphate and histidinol phosphate. J. Biol. Chem. 212: 687–697.Google Scholar
Berlyn, M. B. 1967. Gene-enzyme relationships in histidine biosynthesis in Aspergillus nidulans . Genetics 57: 561–570.CrossRefGoogle ScholarPubMed
Bond, T. J. and Akers, J. 1961. Mechanism of growth inhibition of Escherichia coli by 3-amino 1,2,4-triazole. J. Bacteriol. 81: 327–328.Google Scholar
Brady, D. R. and Houston, L. L. 1973. Some properties of the catalytic sites of imidazoleglycerol phosphate dehydratase–histidinol phosphate phosphatase, a bifunctional enzyme from Salmonella typhimurium . J. Biol. Chem. 248: 2588–2592.Google Scholar
Burns, E. R., Buchanan, G. A., and Carter, M. C. 1971. Inhibition of carotenoid synthesis as a mechanism of action of amitrole, dichlormate and pyriclor. Plant Physiol. 47: 144–148.Google Scholar
Carlomagno, M. S., Chiariotti, L., Alifano, P., Nappo, A. G., and Bruni, C. B. 1988. Structure and function of the Salmonella typhimurium and Escherichia coli K-12 histidine operons. J. Mol. Biol. 203: 585–606.Google Scholar
Carsiotis, M. and Jones, R. F. 1974. Cross pathway regulation: tryptophanemediated control of histidine and arginine biosynthetic enzymes in Neurospora crassa . J. Bacteriol. 119: 889–892.Google Scholar
Chiariotti, L., Nappo, A. G., Carlomagno, M. S., and Bruni, C. B. 1986. Gene structure in the histidine operon of Escherichia coli: identification and nucleotide sequence of the hisB gene. Mol. Gen. Genet. 202: 42–47.Google Scholar
Duggleby, R. G. 1988. Determination of inhibition constants, I 50 values and the type of inhibition for enzyme-catalyzed reactions. Biochem. Med. Metab. Biol. 40: 204–212.Google Scholar
Duke, S. O. 1990. Overview of herbicide mechanisms of action. Environ. Health Perspect. 87: 263–271.Google Scholar
Ebbole, D. J., Paluh, J. L., Plamann, M., Sachs, M. S., and Yanofsky, C. 1991. cpc-1, the general regulatory gene for genes of amino acid biosynthesis in Neurospora crassa, is differentially expressed during the asexual life cycle. Mol. Cell Biol. 11: 928–934.Google Scholar
Fink, G. R. 1964. Gene-enzyme relations in histidine biosynthesis in yeast. Science 146: 525–527.Google Scholar
Flint, D., Emptage, M. H., Finnegan, M. G., Fu, W., and Johnson, M. K. 1993. The role and properties of the iron-sulfur cluster in Escherichia coli dihydroxy-acid dehydratase. J. Biol. Chem. 268: 14732–14742.CrossRefGoogle ScholarPubMed
Glaser, R. D. and Houston, L. L. 1974. Subunit structure and photooxidation of yeast imidazoleglycerolphosphate dehydratase. Biochemistry 13: 5145–5152.Google Scholar
Gottesman, S. 1984. Bacterial regulation: global regulatory networks. Annu. Rev. Genet. 18: 415–441.Google Scholar
Guyer, D., Patton, D., and Ward, E. 1995. Evidence for cross-pathway regulation of metabolic gene expression in plants. Proc. Natl. Acad. Sci. USA 92: 4997–5000.Google Scholar
Hawkes, T. R., Cox, J. M., Barnes, N. J., et al. 1993. Imidazole glycerol phosphate dehydratase: a herbicidal target. in Proceedings of the Brighton Crop Protection Conference—Weeds. Farnham, Great Britain: British Crop Protection Council, pp. 739–744.Google Scholar
Haworth, P. and Siehl, D. L. 1990. Design of enzyme-targeted agrochemicals. J. Agric. Food Chem. 38: 1271–1273.Google Scholar
Heim, D. R. and Larrinua, I. M. 1989. Primary site of action of amitrole in Arabidopsis thaliana involves inhibition of root elongation but not of histidine or pigment biosynthesis. Plant Physiol. 91: 1226–1231.Google Scholar
Hilton, J. L. 1969. Inhibitions of growth and metabolism by 3-amino-1,2,4-triazole (amitrole). J. Agric. Food. Chem. 17: 182–198.Google Scholar
Hilton, J. L., Kearney, P. C., and Ames, B. N. 1965. Mode of action of the herbicide, 3-amino-1,2,4-triazole (amitrole): inhibition of an enzyme of histidine biosynthesis. Arch. Biochem. Biophys. 112: 544–547.CrossRefGoogle ScholarPubMed
Hinnebusch, A. G. 1992. The molecular and cellular biology of the yeast Saccharomyces . In Jones, E. W., Pringle, J. R., and Broach, J. R., eds. Gene Expression. Volume II. Plainview, NY: Cold Spring Harbor Laboratory Press, pp. 319–411.Google Scholar
Johnston, H. M. and Roth, J. R. 1979. Histidine mutants requiring adenine: selection of mutations with reduced hisG expression in Salmonella typhimurium . Genetics. 92: 1–15.CrossRefGoogle ScholarPubMed
Kishore, G. M. and Shah, D. M. 1988. Amino acid biosynthesis inhibitors as herbicides. Annu. Rev. Biochem. 57: 627–663.Google Scholar
Lam, P.Y.S., Jadhav, P. K., Eyermann, C. J., et al. 1994. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science 263: 380–384.Google Scholar
Lauble, H., Kennedy, M. C., Beinert, H., and Stout, C. D. 1992. Crystal structures of aconitase with isocitrate and nitroisocitrate bound. Biochemistry 31: 2735–2748.Google Scholar
Legerton, T. L. and Yanofsky, C. 1985. Cloning and characterization of the multifunctional his3 gene of Neurospora crassa . Gene 39: 129–140.Google Scholar
Loper, J. C. 1961. Enzyme complementation in mixed extracts of mutants from Salmonella histidine B locus. Proc. Natl. Acad. Sci. USA 46: 1440–1450.Google Scholar
Mano, J., Hatano, M., Koizumi, S., Tada, S., Hashimoto, M., and Scheidegger, A. 1993. Purification and properties of a monofunctional imidazoleglycerol–phosphate dehydratase from wheat. Plant Physiol. 103: 733–739.Google Scholar
Matringe, M., Camadro, J.-M., Labbe, P., and Scalla, R. 1989. Protoporphyrinogen oxidase as molecular site for diphenyl ether herbicides. Biochem. J. 260: 232–235.Google Scholar
Mauer, W., Gerber, H. R., and Rufener, J. 1987. CGA 136&872: a new post-emergence herbicide for the selective control of Sorghum spp. and Ecymus repens in Maize. in Proceedings of Brighton Crop Protection Conference—Weeds. Volume 1. Farnham, Great Britain: British Crop Protection Council, pp. 41–48.Google Scholar
Miflin, B. J. 1980. Histidine biosynthesis. in Miflin, B. J., ed. The Biochemistry of Plants. Volume 5. Amino Acids and Derivatives. New York: Academic Press, pp. 533–539.Google Scholar
Moore, J. F., Parker, A. R., Davisson, V. J., and Schwab, J. M. 1993. Stereochemical course of the Escherichia coli imidazoleglycerol phosphate dehydrogenase reaction. J. Am. Chem. Soc. 115: 3338–3339.Google Scholar
Morgaliash, E., Novogrodsky, A., and Schefter, A. 1960. Irreversible reaction of 3-amino-1,2,4-triazole and related inhibitors with the protein catalase. Biochem. J. 74: 339–350.Google Scholar
Mori, I., Fonné-Pfister, R., Matsunaga, S., et al. 1995a. A novel class of herbicide: specific inhibitors of imidazoleglycerol phosphate dehydratase. Plant Physiol. 107: 719–723.Google Scholar
Mori, I., Iwasaki, G., Kimura, Y., et al. 1995b. Synthesis of inhibitors of imidazoleglycerol phosphate dehydratase. J. Am. Chem. Soc. 117: 4411–4412.Google Scholar
Nagai, A., Suzuki, K., Ward, E., Moyer, M., Hashimoto, M., Mano, J., Ohta, D., and Scheidegger, A. 1992a. Overexpression of plant histidinol dehydrogenase using a baculovirus vector system. Arch. Biochem. Biophys. 295: 235–239.Google Scholar
Nagai, A., Suzuki, K., Ward, E., et al. 1992b. Histidinol dehydrogenase in higher plants. Purification, cloning and expression. in Research in Photosynthesis. Volume IV. Dordrecht, The Netherlands: Kluwer Academic Publishers, pp. 95–98.Google Scholar
Niederberger, P., Miozzari, G., and Huetter, R. 1981. Biological role of the general control of amino acid biosynthesis in Saccharomyces cerevisiae . Mol. Cell. Biol. 1: 584–593.Google Scholar
Parker, A. R., Moore, T., Edman, J., Schwab, J. M., and Davisson, V. J. 1994. Cloning, sequence analysis and expression of the gene encoding imidazoleglycerol phosphate dehydratase in Cryptococcus neoformans . Gene 145: 135–138.Google Scholar
Patil, S. S., Kolattukudy, P. E., and Dimond, A. E. 1970. Inhibition of ornitine carbamyl transferase from bean plants by the toxin of Pseudomonas phaseolicola . Plant Physiol. 46: 752–753.Google Scholar
Pillmoor, J. B., Wright, K., and Lindell, S. D. 1991. Herbicide discovery through rational design: some experiences. in Proceedings of the Brighton Crop Protection Conference—Weeds. Farnham, Great Britain: British Crop Protection Council, pp. 857–866.Google Scholar
Pinto, J.E.B.P., Dyer, W. E., Weller, S. C., and Herrmann, K. M. 1988. Glyphosate induces 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase in potato (Solanum tuberosum L.) cells grown in suspension culture. Plant Physiol. 87: 891–893.Google Scholar
Rudiger, W. and Benz, J. 1979. Influence of aminotriazole on the biosynthesis of chlorophyll and phytol. Z. Naturforsch. 34C: 1055–1057.Google Scholar
Saika, H., Früh, T., Iwasaki, G., Koizumi, S., Mori, I., and Hayakawa, K. 1993. Synthesis of (2R, 3R)-, (2S, 3S) (2R, 3S)-, and (2S, 3R)-imidazole glycerol phosphates (IGP): substrates for IGP-dehydratase (IGPD). Bioorg. Med. Chem. Lett. 3: 2129–2134.CrossRefGoogle Scholar
Shaner, D. L. and Singh, B. K. 1992. How does inhibition of amino acid biosynthesis kill plants? in Singh, B. K., Flores, H. E., and Shannon, J. C., eds. Biosynthesis and Molecular Regulation of Amino Acids in Plants. Rockville, MD: American Society of Plant Physiologists, pp. 174–183.Google Scholar
Siehl, D. L. 1992. Considerations in selecting a target site for herbicide design. in Singh, B. K., Flores, H. E., and Shannon, J. C., eds. Biosynthesis and Molecular Regulation of Amino Acids in Plants. Rockville, MD: American Society of Plant Physiologists, pp. 146–162.Google Scholar
Sinden, S. L. and Durbon, R. D. 1968. Glutamate synthetase inhibition: possible mode of action of wildfire toxin from Pseudomonas tabaci . Nature (London) 219: 379–380.Google Scholar
Smith, I. K. 1985. Stimulation of glutathione synthesis in photorespirating plants by catalase inhibitors. Plant Physiol. 79: 1044–1047.Google Scholar
Staples, M. A. and Houston, L. L. 1979. Proteolytic degradation of imidazoleglycerol phosphate dehydratase–histidinol phosphatase from Salmonella typhymurium and the isolation of a resistant bifunctional core enzyme. J. Biol. Chem. 254: 1395–1401.Google Scholar
Steinruecken, H. and Amrhein, N. 1980. The herbicide glyphosate is a potent inhibitor of 5-enolpyruvyl-shikimic acid 3-phosphate synthase. Biochem. Biophys. Res. Commun. 94: 1207–1212.Google Scholar
Struhl, K. 1985. Nucleotide sequence and transcriptional mapping of the yeast pet56-his3-ded1 gene region. Nucleic Acids Res. 13: 8587–8601.Google Scholar
Struhl, K., Cameron, J. R., and Davis, R. W. 1976. Functional genetic expression of eukaryotic DNA in Escherichia coli . Proc. Natl. Acad. Sci. USA 73: 1471–1475.Google Scholar
Struhl, K. and Davis, R. W. 1977. Production of a functional eukaryotic enzyme in Escherichia coli: cloning and expression of the yeast structural gene for imidazoleglycerol phosphate dehydratase (his3). Proc. Natl. Acad. Sci. USA 74: 5255–5259.Google Scholar
Struhl, K. and Davis, R. W. 1981. Transcription of the his3 gene region in Saccharomyces cerevisiae . J. Mol. Biol. 152: 535–552.Google Scholar
Tada, S., Hatano, M., Nakayama, Y., Volrath, S., Guyer, D., Ward, E., and Ohta, D. 1995. Insect cell expression of recombinant imidazoleglycerol phosphate dehydratase of Arabidopsis and wheat and inhibition by triazole herbicides. Plant Physiol. 109: 153–159.Google Scholar
Tada, S., Volrath, S., Guyer, D., Scheidegger, A., Ryals, J., Ohta, D., and Ward, E. 1994. Isolation and characterization of cDNAs encoding imidazoleglycerolphosphate dehydratase from Arabidopsis thaliana . Plant Physiol. 105: 579–583.Google Scholar
von Heijne, G. and Nishikawa, K. 1991. Chloroplast transit peptides: the perfect random coil? FEBS Lett. 278: 1–3.Google Scholar
von Itzstein, M., Wu, W. Y., Kok, G. B., et al. 1993. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature (London) 363: 418–423.Google Scholar
Walsh, C. 1979. Enzymatic reaction mechanisms. New York: W. H. Freeman, p. 542.Google Scholar
Ward, E., Volrath, S., Koizumi, S., Tada, S., Mori, I., and Iwasaki, G., inventors; Ciba-Geigy Corp., assignee. 1994 Apr 29. Herbicide resistant transgenic plants and their preparation. WO 9426909.Google Scholar
Wei, T. P., Ramasubramanian, T. S., Pu, F., and Golden, J. W. 1993. Anabaena sp. strain PCC 7120 bifA gene encoding a sequence specific DNA binding protein cloned by in vivo transcriptional interference selection. J. Bacteriol. 175: 4025–4035.Google Scholar
Wiater, A., Hulanicka, D., and Klopotowski, T. 1971a. Structural requirements for inhibition of yeast imidazoleglycerol phosphate dehydratase by triazole and anion inhibitors. Acta. Biochim. Pol. 18: 289–297.Google Scholar
Wiater, A., Klopotowski, T., and Bagdasarian, G. 1971b. Synergistic inhibition of plant imidazoleglycerol phosphate dehydratase by aminotriazole and phosphate. Acta. Biochim. Pol. 18: 309–314.Google Scholar
Wiater, A., Krajewska-Grynkiewicz, K., and Klopotowski, T. 1971c. Histidine biosynthesis and its regulation in plants. Acta. Biochim. Pol. 18: 299–307.Google Scholar
Winkler, M. E. 1987. Biosynthesis of histidine. In Escherichia coli and Salmonella typhimurium . In Neidhardt, F. C., Ingraham, J. L., Low, K. B., Magasanik, B., Schaechter, M., and Umbarger, H. E., eds. Cellular and Molecular Biology. Volume I. Washington, DC: American Society of Microbiology, pp. 395–411.Google Scholar
Wolfner, M., Yep, D., Messenguy, F., and Fink, G. R. 1975. Integration of amino acid biosynthesis into the cell cycle of Saccharomyces cerevisiae . J. Mol. Biol. 96: 273–290.Google Scholar