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Biochemical Approaches to Herbicide Discovery: Advances in Enzyme Target Identification and Inhibitor Design

Published online by Cambridge University Press:  12 June 2017

Lynn M. Abell
Lynn M. Abell*
Affiliation:
E. I. du Pont de Nemours, Agricultural Products, Stine-Haskell Research Center, Newark, DE 19714
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Abstract

This paper focuses primarily on the means by which biochemical information can be used to identify enzymes which, upon inhibition, produce lethal phenotypes and the enzyme inhibitor design strategies that have the highest probability of not only inhibiting the enzyme but also translating that inhibition into herbicidal efficacy. The identification of an exquisitely lethal target site is the key initial component to this approach and has often been one of the most difficult steps because the attributes of a lethal site have, at best, been ill-defined. An examination of the characteristics of known targets provides some insight as to the definition of a lethal target. Recently, antisense RNA suppression of enzyme translation has been used to determine the extent of inhibition required for toxicity and offers potential as a strategy for identifying lethal target sites. After identification of a lethal target, detailed knowledge of the enzyme's chemical and kinetic mechanism as well as the protein's structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. The advantages and disadvantages of a given type with respect to in vivo efficacy as well as the probability of herbicide resistance development will be discussed.

Keywords

ALS, acetolactate synthase or acetohydroxy acid synthase, E.C. 4.1.3.18GS, glutamine synthetase, E.C. 6.3.1.2EPSPS, 5-enolpyruvylshikimate-3-phosphate synthase, E.C.2.5.1.19KARI, ketol-acid reductoisomerase, E.C. 1.1.1.86IMI, α isopropyl malate isomerase, E.C. 4.2.1.33IPMDH, β isopropyl malate dehydrogenase, E.C. 1.1.1.85GSA-AT, glutamate-1-semialdehyde, E.C. 5.4.3.8TD, threonine deaminase, E.C.4.2.1.16ACCase, acetylCoA carboxylase, E.C.6.4.1.2IGPD, imidazole glycerol phosphate dehydratase, E.C.4.2.1.19PEP, phosphoenolpyruvateIpOHA, [N-isopropyl oxalyl hydroxamate]Hoe 704 [2-dimethyl-phosphinoyl-2-hydroxyacetic acid]PQ, plastoquinonephosphinothricin, (glufosinate) [2-amino-4-(hydroxymethylphosphinyl)butanoic acid]glyphosate, [N-(phosphonomethyl)glycine]gabaculine, [5-amino-l,3-cyclohexadienyl carboxylate]Antisensereaction intermediate analoguesextraneous site inhibitors
Type
Symposium
Information
Weed Science , Volume 44 , Issue 3 , September 1996 , pp. 734 - 742
Copyright
Copyright © 1996 by the Weed Science Society of America 

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References

Literature Cited

1. Abell, L. M., Schloss, J. V., and Rendina, A. R. 1993. Target-site directed herbicide design. Pages 16–37 in Duke, S. O., Menn, J. J., and Plimmer, J. R., eds. Pest Control with Enhanced Environmental Safety. Amer. Chem. Soc. Symp. Ser. 524, Washington, D.C.Google Scholar
2. Aulabaugh, A. and Schloss, J. V. 1990. Oxalyl hydroxamates as reaction-intermediate analogs for ketol-acid reductoisomerase. Biochemistry 29: 2824–2830.Google Scholar
3. Anton, D., Hedstrom, L., Fish, S., and Abeles, R. 1983. Mechanism of enolpyruvyl shikimate-3-phosphate synthase exchange of phosphoenolpyruvate with solvent protons. Biochemistry 22: 5903–5908.CrossRefGoogle Scholar
4. Blackwell, R. D., Murray, A.J.S., and Lea, P. J. 1987. Inhibition of photosynthesis in barley with decreased levels of glutamine synthetase activity. J. Exp. Bot. 38: 1799–1809.Google Scholar
5. Dumas, R., Cornillon-Bertrand, C., Guigue-Talet, P., Genix, P., Douce, R., and Job, D. 1994. Interactions of plant acetohydroxy acid isomerase with reaction intermediate analogues: correlation of the slow, competitive, inhibition kinetics of enzyme activity and herbicidal effects. Biochem. J. 301: 813–820.CrossRefGoogle Scholar
6. Emptage, M. H. 1990. Yeast isopropylmalate isomerase as an ironsulfur protein. Pages 315–328 in Barak, Z., Chipman, D. M., Schloss, J. V., eds. Biosynthesis of Branched Chain Amino Acids. VCH, Weinheim.Google Scholar
7. Gough, S. P., Kannangara, C. G., and von Wettstein, D. 1993. Glutamate 1-semialdehyde aminotransferase as a target for herbicides. Pages 21–27 in Boger, P. and Sandman, G., eds. Target Assays for Modern Herbicides and Related Phytotoxic Compounds. Lewis, Boca Raton, FL.Google Scholar
8. Hausler, R. E., Lea, P. J., and Leegood, R. C. 1994. Control of photosynthesis in barley leaves with reduced activities of glutamine synthetase or glutamate synthase. Planta 194: 418–435.Google Scholar
9. Hawkes, T. R., Cox, J. M., Barnes, N. J., Beautement, K., Edwards, L. S., Kipps, M. R., Langford, M. P., Lewis, T., Ridley, S. M., and Thomas, P. G. 1993. Imidazole glycerol phosphate dehydratase: a herbicide target. Brighton Crop Protection Conference—Weeds. 739–744.Google Scholar
10. Hawkes, T. R., Cox, J. M., Fraser, T.E.M., and Lewis, T. 1993. A herbicidal inhibitor of isopropylmalate isomerase. Z. Naturforsch. 48c: 364–368.Google Scholar
11. Hennig, M., Grimm, B., Jenny, M., Muller, R., and Jansonius, J. N. 1994. Crystallization and preliminary x-ray analysis of wild-type and K272A mutant glutamate-1-semialdehyde aminotransferase from Synechococcus . J. Mol. Biol. 242: 591–594.Google Scholar
12. Hofgen, R., Axelsen, K.B., Kannangara, C. G., Schuttke, I., Pohlenz, H.-D., Willmitzer, L., Grimm, B., and von Wettstein, D. 1994. A visible marker for antisense mRNA expression in plants: inhibition of chlorophyll synthesis with a glutamate-1-semialdehyde aminotransferase antisense gene. Proc. Natl. Acad. Sci. USA 91: 1726–1730.Google Scholar
13. Hofgen, R., Laber, B., Schuttke, I., Klonus, A.-K., Streber, W., and Pohlenz, H.–D. 1995. Repression of acetolactate synthase activity through antisense inhibition and biochemical analysis of transgeneic potato (Solanum tuberosum L. cv. Desiree) plants. Plant Physiol. 107: 469–477.Google ScholarPubMed
14. Hurley, J. H. and Dean, A. M. 1994. Structure of 3-isopropylmalate dehydrogenase in complex with NAD+: ligand-induced loop closing and mechanism for cofactor specificity. Structure 2: 1007–1016.Google Scholar
15. Kaplan, A.P. and Bartlett, P. A. 1991. Synthesis and evaluation of an inhibitor of carboxypeptidase A with a Ki value in the femtomolar range. Biochemistry 30: 8165–8170.Google Scholar
16. Leach, G. E., Devine, M. D., Kirkwood, R. C., and Marshall, G. 1995. Target enzyme-based resistance to acetyl-coenzyme A carboxylase inhibitors in Eleusine indica . Pestic. Biochem. Physiol. 51: 129–136.Google Scholar
17. Lundqvist, T., Rice, J., Hodge, C. N., Basarab, G. S., Pierce, J., and Lindqvist, Y. 1994. Crystal structure of scytalone dehydratase-A disease determinant of the rice pathogen, Magnaporthe grisea . Structure 2: 937–944.Google Scholar
18. Padgette, S. R., Kolacz, K. H., Delannay, X., Re, D. B., LaVallee, B. J., Tinius, C. N., Rhodes, W. K., Otero, Y. I., Barry, G. F., Eichholtz, D. A., Peschke, V. M., Nida, D. L., Taylor, N. B., and Kishore, G. M. 1995. Development, identification and characterization of a glyphosate-tolerant soybean line. Crop Sci. 35: 1451–1461.Google Scholar
19. Pillmoor, J. B., Lindell, S. D., Briggs, G. G., and Wright, K. 1995. The influences of molecular mechanisms of action on herbicide design. Pages 292–303 in Ragsdale, N. N., Kearney, P. C. and Plimmer, J. R., eds. Proceedings Eighth IUPAC International Congress of Pesticide Chemistry. ACS, Washington, D.C. Google Scholar
20. Pohlenz, H-D. and Hofgen, R. 1994. Antisense gene expression as tool for evaluating potential molecular herbicide targets. Eighth IUPAC International Congress of Pesticide Chemistry, July 4–9, Washington, D.C.Google Scholar
21. Ream, J. E., Yuen, H. K., Frazier, R. B., and Sikorski, J. A. 1992. EPSP synthase: binding studies using isothermal titration microcalorimetry and equilibrium dialysis and their implications for ligand recognition and kinetic mechanism. Biochemistry 31: 5528–5534.Google Scholar
22. Rendina, A. R. and Abell, L. M. 1994. Biochemical approaches to herbicide discovery: enzyme target selection and inhibitor design. Pages 407–124 in Hedin, P. A., Menn, J. J., Hollingworth, R. M., eds. Natural and Engineered Pest Management Agents. Amer. Chem. Soc. Symp. Ser. 551., Washington, D.C.Google Scholar
23. Saari, L. L., Cotterman, J. C., and Thill, D. C. 1994. Resistance to acetolactate synthase inhibiting herbicides. Pages 83–139 in Powles, S., Holtum, J. eds. Herbicide Resist. Plants. Lewis, Boca Raton, FL.Google Scholar
24. Sammons, R. D., Gruys, K. J., Anderson, K. S., Johnson, K. A., and Sikorski, J. A. 1995. Re-evaluating glyphosate as a transitionstate inhibitor of EPSPsynthase: identification of an EPSP synthase EPSP glyphosate ternary complex. Biochemistry 34: 6433–6440.Google Scholar
25. Schloss, J. V. 1989. Modern aspects of enzyme inhibition with particular emphasis on reaction intermediate analogs and other potent, reversible inhibitors. Pages 247–282 in Boger, P., Sandmann, G., eds, Target Sites of Herbicide Action. CRC Press, Boca Raton, FL.Google Scholar
26. Schloss, J. V., Ciskanik, L. M., and Van Dyk, D. E. 1988. Origin of the herbicide-binding site of acetolactate synthase. Nature 331: 360–362.Google Scholar
27. Stallings, W. C., Abdel-Meguid, S. S., Lim, S. S., Shieh, H. S., Dayringer, H. E., Leimgruber, N. K., Stegeman, R. S., Anderson, K. S., and Sikorski, J. A. et al. 1991. Structure and topological symmetry of the glyphosate target 5-enolpyruvylshikimate-3-phosphate synthase: A distinctive protein fold. Proc. Natl. Acad. Sci. U.S.A. 88: 5046–5050.Google Scholar
28. Wittenbach, V. A., Aulabaugh, A., and Schloss, J. V. 1991. Examples of extraneous site inhibitors and reaction intermediate analogs: acetolactate synthase and ketol acid reductoisomerase. Pages 151–160 in Frehse, H., ed. Pesticide Chemistry. VCH, Weinheim.Google Scholar
29. Wittenbach, V. A., Rayner, D. R., and Schloss, J. V. 1991. Pressure points in the biosynthetic pathway for branched chain amino acids. Curr. Top. Plant Physiol. 7: 69–88.Google Scholar
30. Wittenbach, V. A., Teaney, P. W., Hanna, W. S., Rayner, D. R., and Schloss, J. V. 1994. Herbicidal activity of an isopropylmalate dehydrogenase inhibitor. Plant Physiol. 106: 321–328.CrossRefGoogle ScholarPubMed
31. Yamashita, M. M., Almassy, R. J., Janson, C. A., Cascio, D., and Eisenberg, D. 1989. Refinded atomic model of glutamine synthetase at 3.5 A resolution. J. Biol. Chem. 264: 17861–17690.Google Scholar