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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
*
[email protected].
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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

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