To get a more potent and safe herbicide two classical methologies had been applied. These can be called $quot;blind screening$quot; method and $quot;me-too$quot; method. In addition to these a new possible approach so called $quot;biorational$quot; method was developed based on the biochemical and physiological knowledge how and where these herbicides show phytotoxicity. The tactics of this methology can be summarized as a trial to get a new novel herbicidally active compound through the biorational design of specific enzyme inhibitors in the metabolic pathway identified as a site of possible induction of proper and selective phytotoxicity. This goa 1 can be achieved by the following steps; 1) choosing the target enzyme for herbicidal action, 2) getting the enzyme, 3) understanding the enzyme and its mechanism, 4) design inhibitors, 5) inhibition test, and 6) field test.
This present action includes an example relating to the enzyme, α,β-dihydroxyacid dehydratase (E.C.4.2.1.9) in the branched-chain amino acid biosynthesis. This enzyme catalyzes the transformation of 2,3-dihydroxyisovaleric acid into 2-oxoisovaleric acid with loss of water. The mechanistic detail of this reaction was studied with deuterium labeling compounds to find out an enol intermediate. Several inhibitors on the basis of this mechanistic knowledge had been designed and screened against this enzyme purified from spinach leaves. The effectiveness and mode of inhibition and field test result will be presented.
Other target sites of herbicide design will be shown with a current research in my laboratory. I also would like to discuss some advantages and disadvantages of this approach, and how successful and how unsuccessful the $quot;biorational design$quot; of herbicide is.
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