Rationale for a natural products approach to herbicide discovery

Abstract

Weeds continue to evolve resistance to all the known modes of herbicidal action, but no herbicide with a new target site has been commercialized in nearly 20 years. The so-called 'new chemistries' are simply molecules belonging to new chemical classes that have the same mechanisms of action as older herbicides (e.g. the protoporphyrinogen-oxidase-inhibiting pyrimidinedione saflufenacil or the very-long-chain fatty acid elongase targeting sulfonylisoxazoline herbicide pyroxasulfone). Therefore, the number of tools to manage weeds, and in particular those that can control herbicide-resistant weeds, is diminishing rapidly. There is an imminent need for truly innovative classes of herbicides that explore chemical spaces and interact with target sites not previously exploited by older active ingredients. This review proposes a rationale for a natural-products-centered approach to herbicide discovery that capitalizes on the structural diversity and ingenuity afforded by these biologically active compounds. The natural process of extended-throughput screening (high number of compounds tested on many potential target sites over long periods of times) that has shaped the evolution of natural products tends to generate molecules tailored to interact with specific target sites. As this review shows, there is generally little overlap between the mode of action of natural and synthetic phytotoxins, and more emphasis should be placed on applying methods that have proved beneficial to the pharmaceutical industry to solve problems in the agrochemical industry.

Allelopathy: driving mechanisms governing its activity in agriculture

“…To date, some commercial herbicides derived from plants or microorganisms that have already been introduced onto the market belong to different chemical groups, with entirely novel MeA (Duke et al 2002;Dayan et al 2012). The need for new herbicide MeA should be emphasized for at least three important reasons: (a) no new herbicide MeA were released onto the market within the past two decades; (b) the number of herbicides launched onto the market is decreasing steadily, especially due to registration issues; and (c) limitations of current herbicides due to herbicide-resistant weeds are increasing (Duke 2012).…”

“…Allelochemicals can improve the potential to discover innovative MeA and can enable the discovery of different chemical moieties. Compared to chemical-based herbicide discovery, further benefits of allelochemical-based herbicide discovery include: reduced environmental impact, higher consumer acceptance and easier registration (Dayan et al 2012).…”

“…In a review that highlighted 30 phytotoxins produced by microorganisms and plants, 23 different MeA were identified (Duke et al 2002). Additionally, twelve new MeA were documented within 14 compounds isolated from microorganisms and four new mechanisms were discovered in compounds from four different plants species (Dayan et al 2012). The main MeA of herbicides include: (a) inhibition of photosystem II electron transport; (b) interruption of respiration and adenosine triphosphate synthesis; (c) mediation by reactive oxygen species (ROS); (d) alternative mechanisms, mainly the action on amino acid synthesis and plant growth regulators (auxins and gibberellins); (e) indirect allelopathic effects ); (f) inhibition of photosystem I; (g) inhibition of tubulin polymerization; and (g) action on RNA polymerase (Duke et al 2002), among others.…”

Biopesticides: State of the Art and Future Opportunities

“…10 Many natural phytotoxins that might be considered biochemical bioherbicides have novel modes of action that might fill this need. 11,12 Weed management is the most costly pest management problem in organic agriculture. 13 In comparison to crop disease and insect management tools, organic farmers have relatively ineffective weed control products.…”

Evaluation of herbicidal potential of depsides from Cladosporium uredinicola, an endophytic fungus found in Guava fruit

“…2,4,5 Recently, herbicidal activity of many natural products isolated from fungi, like stagonalide, 6 stagonolide H, 2 alternethanoxin A and B, 7 lasiodiplodin, 8 ascochlorin, 9 ophiobolin A, 10 deoxaphomin, 11 and ascaulitoxin 12 have been reported.…”