A Novel Class of Herbicides (Specific Inhibitors of Imidazoleglycerol Phosphate Dehydratase)

Abstract

A new mode of herbicidal action was established by finding specific inhibitors of imidazoleglycerol phosphate dehydratase, an enzyme of histidine (His) biosynthesis. Three triazole phosphonates inhibited the reaction of the enzyme with Ki values of 40 f 6.5, 10 f 1.6, and 8.5 2 1.4 nM, respectively, and were highly cytotoxic to cultured plant cells. This effect was completely reversed by the addition of His, proving that the cytotoxicity was primarily caused by the inhibition of His biosynthesis. These inhibitors showed widespectrum, postemergent herbicidal activity at application rates ranging from 0.05 to 2 kg/ha.

Insect Cell Expression of Recombinant Imidazoleglycerolphosphate Dehydratase of Arabidopsis and Wheat and Inhibition by Triazole Herbicides

“…Initial rates were measured in triplicate, and kinetics parameters were obtained by calculating the experimental data using a GraFit program (Erithacus Software, Middlesex, UK). Inhibition by IRL 1803 and 3-amino-1,2,4-triazole was studied as described previously (Mori et al, 1995). One unit of enzyme activity was defined as the amount of enzyme catalyzing the formation of 1 pmol of IAP/min.…”

“…It is also known that 3-amino-l,2,4-triazole inhibits catalase (Smith, 1985). On the other hand, we have recently synthesized a triazole derivative as a new IGPD inhibitor, IRL 1803, and reported that it exhibits remarkable phytotoxic effects in basil cell culture (Mori et al, 1995). The phyotoxicity was completely reversed by the addition of His (Mori et al, 1995).…”

“…Because IRL 1803 was designed on the basis of the substrate structure (Mori et al, 1995), its inhibition should be competitive with respect to the substrate, IGP. Thus, it is difficult to assume the presence of a binding site for IRL 1803 other than the substrate-binding site in the IGPD protein.…”

“…On the other hand, we have recently synthesized a triazole derivative as a new IGPD inhibitor, IRL 1803, and reported that it exhibits remarkable phytotoxic effects in basil cell culture (Mori et al, 1995). The phyotoxicity was completely reversed by the addition of His (Mori et al, 1995). We purified IGPD from wheat germ to apparent homogeneity (Mano et al, 1993) and showed that the plant IGPD is a monofunctional enzyme, lacking the activity of histidino1 phosphatase, which is associated with IGPD as the product of the hisB gene in bacterial cells (Chariotti et al, 1986).…”

“…To achieve maximal activity, all of these IGPDs required 0.4 mM MnCl 2 and 100 ITIM 2-mercaptoethanol. IRL 1803, a newly synthesized IGPD inhibitor (Mori et al, 1995), inhibited both wheat germ IGPD and wheat rIGPD (Wm-IGPD) competitively. On the other hand, the inhibitor displayed a mixed-type inhibition with Arabidopsis rIGPD (A-IGPD).…”