What is missing to create new herbicides and solving the problem of resistance?

In conclusion, based on the analysis of data on the mechanism of herbicide-induced pathogenesis and information on the peculiarities of the sites of action of the most effective classes of herbicides, it is possible to identify research directions that should develop criteria for selecting new sites of herbicides action and roughly outline these criteria as follows.

Firstly, the study of herbicide-induced pathogenesis mechanisms, including the participation of PCD in this process, will allow the development of methods to assess how important a particular metabolic pathway or physiological system is for the plant's vital activity. Accordingly, it will be possible to determine the extent to which disturbances in their functioning can ensure high efficiency of herbicidal action.

Secondly, the study of mechanisms supporting plant organism homeostasis will allow the development of clear criteria for selecting potential herbicide action sites. At present, when choosing a specific enzyme as herbicide action site, it can be used the following characteristics of this enzyme. It is logical to assume that for high herbicidal activity, the content of the enzyme, chosen as the action site, should be low [75]. In addition, the rate of enzyme turnover should not be high.

Despite the insufficiently studied mechanisms of maintaining homeostasis, information about the presence of feedback loops that regulate the expression of the selected enzyme can be taken into account when choosing this enzyme as a site of herbicide action. If it is expected that herbicidal action will be caused by a deficiency of products of the metabolic pathway to which this enzyme belongs, the negative feedback that could lead to increased expression of this enzyme should be absent. This requirement can be implemented if the enzyme catalytic activity requires the presence of cofactors, and the herbicide action leads to their deficiency. A more complex way to implement this requirement lies in the fact that the consequences of herbicide action hinder the expression of the gene encoding its site of action. In this case, a positive feedback loop arises, which strengthens the inhibitory effect of the herbicide. In the case when the herbicidal action is caused by the accumulation of a phytotoxic metabolite that is a substrate of the herbicide-inhibited enzyme, the negative feedback loop will favor the action of the herbicide, but it should be directed not at expression of the enzyme which is the site of action, but at the enzymes preceding it.

It should be recognized, that the mentioned research areas are not in the center of attention of the experts in the field of herbology and weed control. The terms «induced pathogenesis», «programmed cell death», «feedback» are not often found in the titles of articles in weed science related journals [132]. However, in our opinion, studying the mechanisms of herbicide-induced pathogenesis, in particular the PCD participation in this process, as well as the study of feedback loops, that support plant cell homeostasis, will allow to obtain the magic key that will open the way to creating herbicides with new mode of action and solving the problem of weed resistance to herbicides.

herbicide resistance weed cell death

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