Natural products in plant protection

Natural products can be used to control pests and diseases in crops. These products include anorganic compounds, but also a variety of plant extracts. In the beginning of this century active microbial extracts were discovered as well. Synthetic crop protection chemicals were developed from about 1940 onwards and sustained progress in modern agriculture. The first generation chemicals have aspecific modes of toxic action and are in many instances deleterious to the environment. The second generation chemicals have specific modes of action and meet modern environmental requirements. A disadvantage of these chemicals is the potency of target organisms to acquire resistance. This condition urged agrochemical industry to develop chemicals with new modes of action. Such chemicals can be developed by using natural bioactive products as leads in synthesis programmes.This paper decribes the progress that was made in the development of natural bioactive compounds in pest and disease control.     

Role and exploitation of underground chemical signaling in plants

The soil ecosystem is composed of a mixture of living organisms and non‐living matter as well as the complex interactions between them. In the past 100 years or so, agricultural soil ecosystems have been strongly affected by agricultural practices such as tillage and the use of pesticides and fertilizers, which strongly affect soil nutrient composition, pH and biodiversity. In modern pest management, however, the focus is gradually shifting from crop production through agricultural practices to soil ecosystem protection. In this review we discuss how the underground chemical signals secreted by plant roots play a role in keeping the soil ecosystem in balance and how they affect plant fitness by shaping the root biome, increasing nutrient availability, promoting symbiosis, and attracting beneficial organisms and repelling harmful ones, including other plants. We review a number of fascinating cases, such as signaling molecules with dual, positive and negative, functions and bacterial quorum sensing mimicking molecules. Finally, examples of how these compounds can be exploited in modern pest management are reviewed, and the prospects for future developments discussed. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Natural products in plant protection

Natural products can be used to control pests and diseases in crops. These products include anorganic compounds, but also a variety of plant extracts. In the beginning of this century active microbial extracts were discovered as well. Synthetic crop protection chemicals were developed from about 1940 onwards and sustained progress in modern agriculture. The first generation chemicals have aspecific modes of toxic action and are in many instances deleterious to the environment. The second generation chemicals have specific modes of action and meet modern environmental requirements. A disadvantage of these chemicals is the potency of target organisms to acquire resistance. This condition urged agrochemical industry to develop chemicals with new modes of action. Such chemicals can be developed by using natural bioactive products as leads in synthesis programmes. This paper decribes the progress that was made in the development of natural bioactive compounds in pest and disease control.     

The importance of trifluoromethyl pyridines in crop protection

The pyridine ring, substituted by a trifluoromethyl substituent has been successfully incorporated into molecules with useful biological properties. During the period 1990 to September 2017, 14 crop protection products bearing a trifluoromethyl pyridine have been commercialized or proposed for an ISO common name, covering fungicides, herbicides, insecticides and nematicides. Chemical processes have been developed to provide trifluoromethyl pyridine intermediates, from non‐fluorinated pyridine starting materials, at scale and with affordable costs of goods. These attractive starting materials were readily adopted by research chemists, and elaborated through simple chemical modifications into new active ingredients. In a second approach, substituted trifluoromethyl pyridine rings have been constructed from acyclic, trifluoromethyl starting materials, which again has served to identify new active ingredients. Molecular matched pair analysis reveals subtle, yet important differences in physicochemical and agronomic properties of trifluoromethyl pyridines compared with the phenyl analogues. This review focuses on the past 27 years, seeking to identify reasons behind the success of such research programmes, and inspire the search for new crop protection chemicals containing the trifluoromethyl pyridine ring. © 2017 Society of Chemical Industry     

Review: Resistance as a concomitant of modern crop protection

This paper reviews the impact of resistance to fungicides and insecticides/acaricides on the way crop protection is practised. It is now clear that resistance can develop to virtually any crop-protection product, in any pest, fungal pathogen or even weed. As a limiting factor in crop protection, it is a fact of life. A positive side-effect is the precision with which products are used today, with increasing implementation of Integrated Pest Management (IPM) programmes. This is a vital step towards sustainability. This paper describes: past experiences; current status of resistance; how resistance management influences current crop protection practices; regulatory aspects; and the outlook for the future. It concludes that EU regulations on resistance management must be simple and workable. Chemicals will continue to have a central role in optimising yields from the world's crops, as new tools, including biotechnology, become available for crop protection and resistance management. The crop-protection industry's innovations and product stewardship programmes will contribute to sustainable agriculture. This will provide continued benefits to users, the environment and society. ©1997 SCI     

Safe nanotechnologies for increasing the effectiveness of environmentally friendly natural agrochemicals

Natural compounds and living organisms continue to play a limited role in crop protection, and few of them have reached the market, despite their attractiveness and the efforts made in research. Very often these products have negative characteristics compared to synthetic compounds, e.g., higher costs of production, lower effectiveness, lack of persistence, and inability to reach and penetrate the target plant. Conversely, nanotechnologies are having an enormous impact on all human activities, including agriculture, even if the production of some nanomaterials is not environmentally friendly or could have adverse effects on agriculture and the environment. Thus, certain nanomaterials could facilitate the development of formulated natural pesticides, making them more effective and more environmentally friendly. Nanoformulations can improve efficacy, reduce effective doses, and increase shelf‐life and persistence. Such controlled‐release products can improve delivery to the target pest. This review considers certain available nanomaterials and nanotechnologies for use in agriculture, discussing their properties and the feasibility of their use in sustainable crop protection, in particular, in improving the effectiveness of natural bio‐based agrochemicals. © 2019 Society of Chemical Industry     

Neonicotinoids-from zero to hero in insecticide chemistry

In recent years, neonicotinoids have been the fastest-growing class of insecticides in modern crop protection, with widespread use against a broad spectrum of sucking and certain chewing pests. As potent agonists, they act selectively on insect nicotinic acetylcholine receptors, their molecular target site. The discovery of neonicotinoids can be considered as a milestone in insecticide research and facilitates greatly the understanding of the functional properties of insect nicotinic acetylcholine receptors. Because of the relatively low risk for non-target organisms and environment, the high target specificity of neonicotinoid insecticides and their versatility in application methods, this important class has to be maintained globally for integrated pest management strategies and insect resistance management programmes. This review comprehensively describes particularly the origin, structure and bonding as well as associated properties of neonicotinoid insecticides.     

Influence of chlorine substituents on biological activity of chemicals: a review

A number of well known polychlorinated chemicals are toxicologically and environmentally unsafe. Because of their persistence they are in the focus of public discussions against chlorine chemistry. However, chlorinated organic chemicals in the molecular weight range between 200 and 600 constitute an important and indispensable segment in the arsenal of existing biologically active chemicals used as pharmaceuticals or crop‐protection agents. Over the course of time it has been found empirically that the introduction of a chlorine atom into one or more specific positions of a biologically active molecule may substantially improve the intrinsic biological activity. In some cases the presence of a chlorine atom is crucial for significant activity in compounds derived both from nature and chemical synthesis. But in other cases chlorination diminishes or abolishes biological activity, as shown for chlordane homologues. Thus a chlorine atom, like any other substituent, is a modulator of activity. Almost all non‐reactive chlorinated chemicals and chlorine‐free chemicals are devoid of any biological activity at the highest concentration typically used in primary screening tests for discovery of useful biological properties. The influence of a substituent such as chlorine on the biological activity of a potential drug or crop protection agent still has to be established empirically in biological experiments designed to detect desired activity or toxicological properties. Sometimes chlorine does prove to be the optimum for improvement of activity. Long‐term rigorous investigations of several hundred chlorinated compounds, registered by the authorities as pharmaceutical drugs or crop‐protection agents, show that the generalisation ‘all chlorinated chemicals are dangerous’, deduced from the negative toxicological properties of a hundred chlorinated and reactive compounds of low molecular weight that are relevant in terms of safe working conditions in the chemical industry and for ecological safety, is not justified. Chlorinated compounds are not necessarily toxic or dangerous. Highly reactive chemicals or polychlorinated compounds cannot be compared with regard to toxicological properties with unreactive compounds having a low degree of chlorination. The chlorine atom, as one of many possible substituents used in synthetic organic chemistry, will remain in the future one of the important tools for probing structure–activity relationships in life science research and as a molecular component in commercialised compounds, in order to provide safer, more selective and more environmentally compatible products with higher activity for medicine and agriculture. © 1999 WILEY‐VCH Verlag GmbH     

Recent advances in allelopathy for weed control: from knowledge to applications

Allelopathy is the biological phenomenon of chemical interactions between living organisms in the ecosystem, and must be taken into account in addressing pest and weed problems in future sustainable agriculture. Allelopathy is a multidisciplinary science, but in some cases, aspects of its chemistry are overlooked, despite the need for a deep knowledge of the chemical structural characteristics of allelochemicals to facilitate the design of new herbicides. This review is focused on the most important advances in allelopathy, paying particular attention to the design and development of phenolic compounds, terpenoids and alkaloids as herbicides. The isolation of allelochemicals is mainly addressed, but other aspects such as the analysis and activities of derivatives or analogs are also covered. Furthermore, the use of allelopathy in the fight against parasitic plants is included. The past 12 years have been a prolific period for publications on allelopathy. This critical review discusses future research areas in this field and the state of the art is analyzed from the chemist's perspective. © 2019 Society of Chemical Industry     

Dung‐inhabiting fungi: a potential reservoir of novel secondary metabolites for the control of plant pathogens

Coprophilous fungi are a large group of saprotrophic fungi mostly found in herbivore dung. The number of these fungi undergoing investigation is continually increasing, and new species and genera continue to be described. Dung‐inhabiting fungi play an important ecological role in decomposing and recycling nutrients from animal dung. They produce a large array of bioactive secondary metabolites and have a potent enzymatic arsenal able to utilise even complex molecules. Bioactive secondary metabolites are actively involved in interaction with and defence against other organisms whose growth can be inhibited, resulting in an enhanced ecological fitness of producer strains. Currently, these antibiotics and bioactive secondary metabolites are of interest in medicine in particular, while very little information is available concerning their potential use in agriculture. This review introduces the ecology of dung‐inhabiting fungi, with particular emphasis on the production of antibiotic compounds as a means to compete with other microorganisms. Owing to the fast pace of technological progress, new approaches to predicting the biosynthesis of bioactive metabolites are proposed. Coprophilous fungi should be considered as elite candidate organisms for the discovery of novel antifungal compounds, above all in view of their exploitation for crop protection. © 2015 Society of Chemical Industry     

Challenges faced by the IR-4 Programme and US specialty crop growers

The Food Quality Protection Act (FQPA) was enacted in August 1996 and required the US Environmental Protection Agency (EPA) to reassess all existing and new crop protection active substances using a new set of health and environmental standards to further protect infants and children. The initial fear that many minor or specialty crop use registrations would be lost without adequate replacements has largely been overcome by an aggressive programme by the International Research Project no. 4 (IR-4) in partnership with the EPA and the crop protection industry to register new, safer, reduced risk products for specialty crop pest control needs. Since the FQPA, the EPA has approved over 5600 new specialty crop uses resulting from IR-4 residue programmes. This amounts to about 56% of the over 10 000 clearances received by the IR-4 programme in its 43 year history and about 50% of all new uses granted by the EPA since FQPA. The positive outcomes from these efforts have been partially negated by the lack of tolerances or Maximum Residue Levels (MRLs) in countries to which US produce is exported. This has forced some US specialty crop growers to continue to use older, less desirable products. IR-4 has been addressing this challenge by cooperating in the NAFTA (North American Free Trade Agreement) countries with Agriculture and Agri-Food Canada's Pest Management Centre and Health Canada's Pest Management Regulatory Agency to harmonize MRLs through joint projects and regulatory reviews. IR-4 has also provided leadership for the International Crop Grouping Consulting Committee to harmonize specialty/minor crop groupings and representative crops for residue studies with the long-term goal being to globally harmonize MRLs.     

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     

The Hordeum vulgare subsp. spontaneum–Blumeria graminis f. sp. hordei pathosystem: its position in resistance research and breeding applications

Barley (Hordeum vulgare L.) is an important cereal crop and powdery mildew, caused by Blumeria graminis f. sp. hordei, is one of the most serious diseases that occurs on barley throughout the world. In the Middle East, which is the centre of diversity for barley and its pathogens, the wild barley–powdery mildew pathosystem co-evolves resulting in many specific resistances in the host as well as corresponding virulences in the pathogen. Many specific resistances have been used in European breeding programmes and a centre of pathogen diversity has arisen also especially in central Europe. This short review briefly summarizes the use of host resistances derived from wild barley and land races including the durable resistance gene mlo. The use of powdery mildew pathogenicity for studying new and unknown specific resistances and for identifying resistances in commercial varieties is described. However, highly heterogeneous wild barley is also characterized as a valuable source of minor genes for powdery mildew resistance. These might be exploited by barley breeders especially for winter barley improvement where the non-specific resistance gene mlo cannot be used.     

Botanical Pesticides and Their Mode of Action

Pest management is facing economic and ecological challenge worldwide due to human and environmental hazards caused by majority of the synthetic pesticide chemicals. Identification of novel effective insecticidal compounds is essential to combat increasing resistance rates. Botanical pesticides have long been touted as attractive alternatives to synthetic chemical pesticides for pest management because botanicals reputedly pose little threat to the environment or to human health. The body of scientific literature documenting bioactivity of plant derivatives to arthropod pests continues to expand, yet only a handful of botanicals are currently used in agriculture in the industrialized world, and there are few prospects for commercial development of new botanical products. Pyrethrum and neem are well established commercially, pesticides based on plant essential oils have entered the marketplace, and the use of rotenone appears to be waning. A number of plant substances have been considered for use as pest antifeedants, repellents and toxicants, but apart from some natural mosquito repellents, a little commercial success has ensued for plant substances that modify arthropod behavior. Several factors appear to limit the success of botanicals, most notably regulatory barriers and the availability of competing products (newer synthetics and fermentation products) that are cost-effective and relatively safe compared with their predecessors. In the context of agricultural pest management, botanical pesticides are best suited for use in organic food production in industrialized countries but can play a much greater role in the production and postharvest protection of food in developing countries. Botanicals have been in use for a long time for pest control. The compounds offer many environmental advantages. However, their uses during the 20th century have been rather marginal compared with other bio-control methods of pests and pathogens. Improvement in the understanding of plant allelochemical mechanisms of activity offer new prospects for using these substances in crop protection. I’m trying in this article to present different kinds of botanical pesticides came from different recourses and their mode of actions as well as I will try to examine the reasons behind their limited use (disadvantages) and the actual crop protection developments involving biopesticides of plant origin for organic or traditional agricultures to keep our environment clean and safer for humankind and animals.     

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     

Dealing with transgene flow of crop protection traits from crops to their relatives

Genes regularly move within species, to/from crops, as well as to their con‐ specific progenitors, feral and weedy forms (‘vertical’ gene flow). Genes occasionally move to/from crops and their distantly related, hardly sexually interbreeding relatives, within a genus or among closely related genera (diagonal gene flow). Regulators have singled out transgene flow as an issue, yet non‐transgenic herbicide resistance traits pose equal problems, which cannot be mitigated. The risks are quite different from genes flowing to natural (wild) ecosystems versus ruderal and agroecosystems. Transgenic herbicide resistance poses a major risk if introgressed into weedy relatives; disease and insect resistance less so. Technologies have been proposed to contain genes within crops (chloroplast transformation, male sterility) that imperfectly prevent gene flow by pollen to the wild. Containment does not prevent related weeds from pollinating crops. Repeated backcrossing with weeds as pollen parents results in gene establishment in the weeds. Transgenic mitigation relies on coupling crop protection traits in a tandem construct with traits that lower the fitness of the related weeds. Mitigation traits can be morphological (dwarfing, no seed shatter) or chemical (sensitivity to a chemical used later in a rotation). Tandem mitigation traits are genetically linked and will move together. Mitigation traits can also be spread by inserting them in multicopy transposons which disperse faster than the crop protection genes in related weeds. Thus, there are gene flow risks mainly to weeds from some crop protection traits; risks that can and should be dealt with. © 2014 Society of Chemical Industry     

Metabolomics - A robust bioanalytical approach for the discovery of the modes-of-action of pesticides: A review

The agrochemical industry is facing great undertaking that includes increasing demand for the development of new crop protection agents that are safe for the environment and the consumers, and at the same time combat the issue of the emergence of resistance pest strains. The mode-of-action (MoA) is among the features of a bioactive compound that largely determine whether the abovementioned issues are addressed or not, and subsequently whether its commercial development will be addressed. The early discovery of the MoA of bioactive compounds could accelerate pesticide research and development by reducing the required time and costs. Based on advances in synthetic and natural product chemistry, scientists have access to a vast number of compounds that could potentially be developed as crop protection agents. The screening of such compounds with respect to their MoA requires accurate and robust bioanalytical tools. Metabolomics is a powerful bioanalytical tool that will likely play a significant role in the acceleration of the discovery of MoA of bioactive compounds. In the present review, the capabilities and principles and applications of metabolomics for the study of the MoA of herbicides, insecticides, acaricides, fungicides, and antibiotics are discussed.     

The commercial use of azadirachtin and its integration into viable pest control programmes

With the continued robust growth of the global biopesticide market, azadirachtin is uniquely positioned to become a key insecticide to expand in this market segment. In the USA the actual or impending cancellation of some organophosphate and carbamate insecticides that have either lost patent protection or are not being re-registered in many markets because of the Food Quality Protection Act of 1996, has opened new opportunities for biopesticides and reduced-risk pesticides in general. The broad-spectrum activity of azadirachtin at low use rates (12·5 to 40 g AI ha^-1) coupled with the insect growth regulator activity (in all larval/nymphal instars including the pupal stage) and unique mode of action (ecdysone disruptor), make azadirachtin an ideal candidate for insecticide resistance, integrated pest control and organic pest control programmes. Azadirachtin has been exempted from residue tolerance requirements by the US Environmental Protection Agency for food crop applications. Azadirachtin exhibits good efficacy against key pests such as whiteflies, leafminers, fungus gnats, thrips, aphids and many leaf-eating caterpillars. Azadirachtin has minimal to no impact on non-target organisms, is compatible with other biological control agents and has a good fit into classical Integrated Pest Management programmes. The world's largest azadirachtin extraction facility has been fully commissioned in India to process over 10,000 tonnes neem seeds per annum. This will ensure the wide availability of azadirachtin technical grade material in the future. © 1998 Society of Chemical Industry.     

农用抗生素的筛选策略

微生物是具有农用生物活性的代谢产物的重要来源。本文将就筛选策略对近年来从微生物中筛选具有农用生物活性代谢产物即农用抗茸素所取得的进展进行综述，其中包括分离新的或稀有微生物类群、发酵技术的改进、建立新的筛选模型及高通量筛选技术及色谱-光谱联用技术等方面。新的微生物类群是产生新的具有农用生物活性的代谢产物的重要目标；发酵技术的改进将会提高新的代谢产物出现的机会和检测的机率；新的筛选模型的创建和改进有助于发现新的代谢产物；高通量筛选技术有助于提高筛选的速度;而色谱-光谱联用技术的运用将避免不必要的重复工作，加快化合物的早期鉴别速度。     

Molecular basis of specificity in host/fungus interactions

Fungal phytopathogens have evolved efficient mechanisms that enable them to exploit the plant nutrient reservoir for the purpose of growth and propagation. These are counteracted by the plants to arrest fungal development. Two general principles control the specificity of host/fungus interactions. In several cases, the interplay between fungus-produced toxins and either plant toxin targets or detoxification mechanisms determine the outcome of the interaction. An analogous principle appears to be operative in the opposite direction; deposition by plants of fungitoxic compounds that can be detoxified by pathogenic fungi. Presumably of more general importance is the recognition-based plant defense system. The ensuing resistance is frequently controlled by single genes in both interacting organisms. Originally observed in many crop plants at the sub-species level, it has recently also been described in wild plants and at the species level. The structures of disease resistance genes cloned to date from different plants allow the conclusion that the plant protective system against pathogens is based on a general principle that appears to be as effective as the animal disease protection system.