A novel genomic approach to herbicide and herbicide mode of action discovery

A herbicide with a new mode of action has not been commercialized for more than 30 years. A recent paper describes a novel genomic approach to herbicide and herbicide mode of action discovery. Analysis of a microbial gene cluster revealed that it encodes genes for both the biosynthetic pathway for production of the sesquiterpene aspterric acid and an aspterric acid‐resistant form of dihydroxy acid dehydratase (DHAD), its target enzyme. Aspterric acid is weak compared with commercial synthetic herbicides, and whether DHAD is a good herbicide target is unclear from this study. Nevertheless, this genomic approach provides a novel strategy for the discovery of herbicides with new modes action. © 2018 Society of Chemical Industry     

Natural products: a strategic lead generation approach in crop protection discovery

With the anticipated population growth in the coming decades, the changing regulatory environment, and the continued emergence of resistance to commercial pesticides, there is a constant need to discover new lead chemistries with novel modes of action. We have established a portfolio of approaches to accelerate lead generation. One of these approaches capitalizes on the rich bioactivity of natural products (NPs), highlighted by the numerous examples of NP‐based crop protection compounds. Within Corteva Agriscience and the affiliated preceding companies, NPs have been a fruitful approach, for nearly three decades, to identifying and bringing to the market crop protection products inspired by or originating from NPs, . Included in these NP‐based crop protection products are the spinosyns family of insecticides, and those from more recent areas of NP‐based fungicidal chemistry, as highlighted in this perspective. © 2019 Society of Chemical Industry     

Allelopathy--a natural alternative for weed control

Allelopathy studies the interactions among plants, fungi, algae and bacteria with the organisms living in a certain ecosystem, interactions that are mediated by the secondary metabolites produced and exuded into the environment. Consequently, allelopathy is a multidisciplinary science where ecologists, chemists, soil scientists, agronomists, biologists, plant physiologists and molecular biologists offer their skills to give an overall view of the complex interactions occurring in a certain ecosystem. As a result of these studies, applications in weed and pest management are expected in such different fields as development of new agrochemicals, cultural methods, developing of allelopathic crops with increased weed resistance, etc. The present paper will focus on the chemical aspects of allelopathy, pointing out the most recent advances in the chemicals disclosed, their mode of action and their fate in the ecosystem. Also, attention will be paid to achievements in genomics and proteomics, two emerging fields in allelopathy. Rather than being exhaustive, this paper is intended to reflect a critical vision of the current state of allelopathy and to point to future lines of research where in the authors' opinion the main advances and applications could and should be expected.     

Potential roles for microbial endophytes in herbicide tolerance in plants

Herbicide tolerance in crops and weeds is considered to be monotrophic, i.e. determined by the relative susceptibility of the physiological process targeted and the plant's ability to metabolise and detoxify the agrochemical. A growing body of evidence now suggests that endophytes, microbes that inhabit plant tissues and provide a range of growth, health and defence enhancements, can contribute to other types of abiotic and biotic stress tolerance. The current evidence for herbicide tolerance being bitrophic, with both free‐living and plant‐associated endophytes contributing to tolerance in the host plant, has been reviewed. We propose that endophytes can directly contribute to herbicide detoxification through their ability to metabolise xenobiotics. In addition, we explore the paradigm that microbes can ‘prime’ resistance mechanisms in plants such that they enhance herbicide tolerance by inducing the host's stress responses to withstand the downstream toxicity caused by herbicides. This latter mechanism has the potential to contribute to the growth of non‐target‐site‐based herbicide resistance in weeds. Microbial endophytes already contribute to herbicide detoxification in planta, and there is now significant scope to extend these interactions using synthetic biology approaches to engineer new chemical tolerance traits into crops via microbial engineering. © 2015 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

天然除草活性化合物研究进展

综述了近年来国内外从天然产物中开发具有除草活性化合物的研究概况,着重介绍一些可能具有除草剂开发潜力的植物和微生物源化合物,并对生物除草剂的发展前景进行了展望.     

Natural products that have been used commercially as crop protection agents

Many compounds derived from living organisms have found a use in crop protection. These compounds have formed the basis of chemical synthesis programmes to derive new chemical products; they have been used to identify new biochemical modes of action that can be exploited by industry-led discovery programmes; some have been used as starting materials for semi-synthetic derivatives; and many have been used or continue to be used directly as crop protection agents. This review examines only those compounds derived from living organisms that are currently used as pesticides. Plant growth regulators and semiochemicals have been excluded from the review, as have living organisms that exert their effects by the production of biologically active secondary metabolites.     

Mechanism of action and selectivity of a novel herbicide,fenquinotrione

Fenquinotrione is a novel herbicide that can control a wide range of broadleaf and sedge weeds with excellent rice selectivity. We revealed that fenquinotrione potently inhibited the 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity in Arabidopsis thaliana with an IC₅₀ of 44.7 nM. The docking study suggested that the 1,3-diketone moiety of fenquinotrione formed a bidentate interaction with Fe(II) at the active site. Furthermore, π–π stacking interactions occurred between the oxoquinoxaline ring and the conserved Phe409 and Phe452 rings, indicating that fenquinotrione competes with the substrate, similar to existing HPPD inhibitors. A more than 16-fold difference in the herbicidal activity of fenquinotrione in rice and the sedge, Schoenoplectus juncoides, was observed. However, fenquinotrione showed high inhibitory activity against rice HPPD. Comparative metabolism study suggested that the potent demethylating metabolism followed by glucose conjugation in rice was responsible for the selectivity of fenquinotrione.     

Chlorophyll fluorescence as a marker for herbicide mechanisms of action

Photosynthesis is the single most important source of O₂ and organic chemical energy necessary to support all non-autotrophic life forms. Plants compartmentalize this elaborate biochemical process within chloroplasts in order to safely harness the power of solar energy and convert it into usable chemical units. Stresses (biotic or abiotic) that challenge the integrity of the plant cell are likely to affect photosynthesis and alter chlorophyll fluorescence. A simple three-step assay was developed to test selected herbicides representative of the known herbicide mechanisms of action and a number of natural phytotoxins to determine their effect on photosynthesis as measured by chlorophyll fluorescence. The most active compounds were those interacting directly with photosynthesis (inhibitors of photosystem I and II), those inhibiting carotenoid synthesis, and those with mechanisms of action generating reactive oxygen species and lipid peroxidation (uncouplers and inhibitors of protoporphyrinogen oxidase). Other active compounds targeted lipids (very-long-chain fatty acid synthase and removal of cuticular waxes). Therefore, induced chlorophyll fluorescence is a good biomarker to help identify certain herbicide modes of action and their dependence on light for bioactivity.     

Pesticidal natural products – status and future potential

There is a long history of using natural products as the basis for creating new pesticides but there is still a relatively low percentage of naturally derived pesticides relative to the number of pharmaceuticals derived from natural sources. Biopesticides as defined and regulated by the US Environmental Protection Agency (EPA) have been around for 70 years, starting with Bacillus thuringiensis, but they are experiencing rapid growth as the products have got better and more science‐based, and there are more restrictions on synthetic chemical pesticides. As such, biopesticides are still a small percentage (approximately US$3–4 billion) of the US$61.3 billion pesticide market. The growth of biopesticides is projected to outpace that of chemical pesticides, with compounded annual growth rates of between 10% and 20%. When integrated into crop production and pest management programs, biopesticides offer the potential for higher crop yields and quality than chemical‐only programs. Added benefits include reduction or elimination of chemical residues, therefore easing export, enabling delay in the development of resistance by pests and pathogens to chemicals and shorter field re‐entry, biodegradability and production using agricultural raw materials versus fossil fuels, and low risk to non‐target organisms, including pollinators. Challenges to the adoption of biopesticides include lack of awareness and education in how to deploy their unique modes of action in integrated programs, testing products alone versus in integrated programs, and lingering perceptions of cost and efficacy. © 2019 Society of Chemical Industry     

From synthetic control to natural products: a focus on N‐heterocycles

Natural products containing a N‐heterocycle motif are widespread in nature and medicinal plants, in particular, have proved to be a source of almost unlimited N‐derived structures with high molecular diversity. Because of their intrinsic potential for use in both biomedical and agricultural applications, there is a general need for new compounds and for the synthesis of ‘natural‐inspired’ analogues. Importantly, transition of a natural product from discovery to a ‘market lead’ is associated with an increasingly challenging demand for more of the compound, which cannot be met by isolation from natural plant sources, often due to low extraction yields and uneven availability of the plant source itself. Synthesis remains the most reliable approach to provide valuable products for the market. In this review, a comprehensive overview of our contribution to synthetic access to N‐derived natural products is given. Major strengths of the proposed methodologies are discussed critically. © 2019 Society of Chemical Industry     

Natural products in agriculture—a view from the industry

The paper discusses the use of natural products and biological control agents in crop protection from an industrial viewpoint. The criteria which must be satisfied are noted. Examples are given from the genetic engineering of baculoviruses and proteins. The final section considers the utility of natural products as a source of leads for conventional agrochemicals, and the screens needed. © 1998 SCI.     

Plant cell membrane as a marker for light-dependent and light-independent herbicide mechanisms of action

Plant cells possess a number of membrane bound organelles that play important roles in compartmentalizing a large number of biochemical pathways and physiological functions that have potentially harmful intermediates or by-products. The plasma membrane is particularly important as it holds the entire cellular structure whole and is at the interface between the cell and its environment. Consequently, breaches in the integrity of the lipid bilayer, often via reactive oxygen species (ROS)-induced stress membrane peroxidation, result in uncontrolled electrolyte leakage and in cell death. A simple 3-step bioassay was developed to identify compounds that cause electrolyte leakage and to differentiate light-dependent mechanisms of action from those that work in darkness. Herbicides representative of all known modes of action (as well as several natural phytotoxins) were selected to survey their effects on membrane integrity of cucumber cotyledon discs. The most active compounds were those that are known to generate ROS such as the electron diverters and uncouplers (paraquat and dinoterb) and those that either were photodynamic (cercosporin) or caused the accumulation of photodynamic products (acifluorfen-methyl and sulfentrazone). Other active compounds targeted lipids (diclofop-methyl, triclosan and pelargonic acid) or formed pores in the plasma membrane (syringomycin). Herbicides that inhibit amino acid, protein, nucleotide, cell wall or microtubule synthesis did not have any effect. Therefore, it was concluded that the plant plasma membrane is a good biomarker to help identify certain herbicide modes of action and their dependence on light for bioactivity.     

Status and outlook for acaricide and insecticide discovery

To guarantee sustainability and progress, the agrochemical industry is faced with several major challenges. Currently, loss of active ingredients due to consumer perception, changing grower needs and ever‐changing regulatory requirements is far higher than the number being introduced into the market. Therefore, there is a need to develop new products that can provide improved efficacy, selectivity and favorable environmental profiles. Strategies to achieve these goals are the search for acaricides and insecticides with new modes of action, or the discovery of novel molecules with activity on the most attractive target sites having resistance breaking properties against pest species. In this context, the introduction of halogen atoms or asymmetric centers into an active ingredient remains an important tool to modulate their properties, but so too is the pro‐pesticide concept. This review gives an overview of agrochemicals launched over the past 8 years, reflects new insights into known mechanisms of action, and describes the status and outlook for acaricide and insecticide discovery.     

微生物及其天然产物防治杂草的发展及展望

概述了利用微生物及其天然产物防治杂草的潜在优势和研究进展，介绍已商品化和具有开发潜力的微生物除草剂及具有除草活性的微生物天然植物毒素。     

Physionomics and metabolomics-two key approaches in herbicidal mode of action discovery

BACKGROUND: For novel herbicides identified in greenhouse screens, efficient research is important to discover and chemically optimise new leads with new modes of action (MoAs). RESULTS: The metabolic and physiological response pattern to a herbicide can be viewed as the result of changes elicited in the molecular and biochemical process chain. These response patterns are diagnostic of a herbicide's MoA. At the starting point of MoA characterisation, an array of bioassays is used for comprehensive physiological profiling of herbicide effects. This physionomics approach enables discrimination between known, novel or multiple MoAs of a compound and provides a first clue to a new MoA. Metabolic profiling is performed with the use of treated Lemna paucicostata plants. After plant extraction and chromatography and mass spectrometry, changes in levels of approximately 200 identified and 300 unknown analytes are quantified. Check for known MoA assignment is performed by multivariate statistical data analyses. Distinct metabolite changes, which can direct to an affected enzymatic step, are visualised in a biochemical pathway view. Subsequent target identification includes metabolite feeding and molecular, biochemical and microscopic methods. CONCLUSION: The value of this cascade strategy is exemplified by new herbicides with MoAs in plastoquinone, auxin or very‐long‐chain fatty acid synthesis. Copyright © 2011 Society of Chemical Industry     

植物源农药研究进展(综述)

与传统化学杀虫剂相比,植物源天然产物杀虫剂具有靶标特异性强、易降解无残留、对环境无污染等优点,符合绿色农业的发展要求,是杀虫剂研发的重要领域之一。本文围绕不同类型植物源天然产物杀虫剂的结构特征和作用机制,综述了2015年之后以植物源杀虫剂活性成分为先导化合物进行结构改造的研究现状,最后对植物源农药的发展方向、当前面临的挑战以及产品研发策略进行了分析和展望。     

Cold plasma: a potential new method to manage postharvest diseases caused by fungal plant pathogens

Development of alternative, chemical‐free approaches for control of postharvest fungi on a commercial scale has become a challenge for plant pathologists in recent years. Although there are several established techniques such as heat that are used as postharvest treatments, they often have disadvantages, including alteration of food quality due to physiological responses to the treatment, or environmental pollution. A promising new postharvest treatment is cold plasma, which is a gas‐derived mix of atoms, excited molecules and charged particles. Cold plasma has no known adverse effects on fresh produce or the environment. It is an established technology in the medical field and has been demonstrated to successfully control bacterial pathogens that cause food safety issues. This review focuses on the potential of cold plasma technology for postharvest disease control, especially those caused by fungi. An overview of plasma generation systems is provided, and in vivo and in vitro research is reviewed to consider benefits, limitations and research gaps in the context of cold plasma as a potential method for controlling postharvest fungal pathogens. Finally, recommendations are provided for the application of this technology in commercial facilities.