Natural compounds as next-generation herbicides

Abstract

Herbicides with new modes of action (MOAs) are badly needed due to the rapidly evolving resistance to commercial herbicides, but a new MOA has not been introduced in over 20 years. The greatest pest management challenge for organic agriculture is the lack of effective natural product herbicides. The structural diversity and evolved biological activity of natural phytotoxins offer opportunities for the development of both directly used natural compounds and synthetic herbicides with new target sites based on the structures of natural phytotoxins. Natural phytotoxins are also a source for the discovery of new herbicide target sites that can serve as the focus of traditional herbicide discovery efforts. There are many examples of strong natural phytotoxins with MOAs other than those used by commercial herbicides, which indicates that there are molecular targets of herbicides that can be added to the current repertoire of commercial herbicide MOAs.

Figure 1.

Amino acid biosynthesis pathways showing the enzymatic target sites of natural compound phytotoxins. 1, GS, the target site of phosphinothricin; 2, Orn carbamoyl transferase, the target site of phaseolotoxin; 3, Trp synthase, the target site of 5-methyl-Trp; 4, Asp transaminase, the target site of gostatin; 5, β-cystathionase, the target site of rhizobitoxine. PEP, Phosphoenolpyruvate.

Figure 2.

Various target sites of natural products that interfere with various aspects of the light reaction of photosynthesis within the thylakoid membrane. 1, The Q_B binding site of plastoquinone, the target site of sorgoleone; 2, electron flow between PSII and the cytochrome b₆/f complex, the target site of aurachins; 3, pyridazocidin diverts electrons from PSI; 4, the target site of nigericin, which uncouples photophosphorylation; 5, chloroplast CF1 ATPase, the target site of tentoxin. The dotted black line illustrates the flow of electrons from the oxygen-evolving complex to ferredoxin-NADP⁺ reductase. Solid black lines illustrate the accumulation of the proton gradient inside the lumen and its use by CF1 ATPase to synthesize ATP. FD, Ferredoxin; FNR, ferredoxin-NADP⁺ reductase; OEC, oxygen-evolving complex; PC, plastocyanin; Pi, inorganic phosphate; PQ, plastoquinone; PQH₂, reduced PQ.

Figure 3.

Simplified pathways of chlorophyll (green) and carotenoid (orange) biosynthesis. These two pathways are connected via the phytyl tail, originating from the chloroplastic isoprenoid geranylgeranyl pyrophosphate (PP). The pathway of prenylquinones, shown in purple, is also important for carotenoid biosynthesis because plastoquinone is an essential cofactor for PDS activity. Solid lines represent single reactions, and the dotted line represents many steps. 1, Glu-1-semialdehyde aminotransferase, the target site of gabaculine; 2, protoporphyrinogen oxidase, one of the target sites of cyperin; 3, deoxyxylulose-5-phosphate reductase, the target site of fosmidomycin; 4, p-hydroxyphenylpyruvate dioxygenase, the target site of natural β-triketones such as leptospermone; 5, tyrosine aminotransferase, the target site of the 1,4-cineole-derived herbicide cinmethylin.

Figure 4.

Simplified pathways of lipid biosynthesis, showing target sites of natural phytotoxins. Fatty acid synthesis initiates in the mitochondria. The biosynthesis of ceramide, which leads to the production of cerebrosides, is localized in the endoplasmic reticulum (ER). 1, β-Ketoacyl-ACP synthase, the target site of thiolactomycin; 2, ENR, one of the target sites of cyperin; 3, ceramide synthase, the target site of AAL-toxins and fumonisins.

Figure 5.

Membrane functions and lipid stability are affected by natural products. 1, Plasma membrane H⁺-ATPase, the target site of sorgoleone and juglone; 2, auxin-induced and constitutive NADH oxidases, the target sites of fusicoccin and simalikalactone D, respectively; 3, loss of membrane integrity by the self-assembly of large amphiphilic molecules (such as syringomycin) to form pores; 4, loss of membrane integrity by natural products such as cercosporin that generate large amounts of reactive oxygen species (ROS). Pi, Inorganic phosphate.

Figure 6.

Cell macrostructures affected by natural products. 1, Microtubule polymerization is affected by citral; 2, cellulose synthase (CESA) is the target site of thaxtomin; 3, Golgi body structural integrity is disrupted by brefeldin A.