Three root-parasitic witchweed (Striga) species can cause up to total loss of grain and legume crops for millions of farmers in Africa. The damage is initiated before Striga emerges from the soil. Four decades of resistance breeding, especially maize, have at best conferred localized moderate resistance that has not greatly increased yields. Recent innovative basic research has led to major advances that are herein evaluated in biocontrol, formulating suicidal germination stimulants and gene-edited crops. A mycoherbicide was able to become a commercial success because the innovators rendered the fungus hypervirulent, inexpensively cultivated it, formulated it as a seedcoat with ample nutrition for extensive growth, and determined target species specificity for regulators. A slow-release formulation of suicidal germination stimulants led to a Striga-free crop, but crop planting had to be impractically delayed by almost 3 months for the technology to work. Elegant basic research led to gene-edited crop plants secreting vastly reduced levels of Striga germination stimulant, leading to Striga asiatica-free fields under low seeding levels of the parasite. It is doubted that the results will carry over to fields infested with the far more virulent Striga hermonthica having seedbanks so large that the residual amount of stimulant emitted may result in heavy infestation. The editing approach should be extended to suppressing the genes responsible for Striga attachment and establishment, and the genes stacked for more robust resistance. Solving only the Striga problem is insufficient because farmers with Striga are also confronted with insect, pathogen and climate constraints that need simultaneous solutions. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

A triple-peaked UV-blue photoacceptor was first found in fungi and nicknamed cryptochrome due to its being cryptic and found then only in cryptogamous plants. It was subsequently discovered in higher plants and even later in algae, insects, fish, amphibians, and mammals including humans. Cryptochrome is the photoacceptor controlling a plethora of properties in all these systems.

Despite major breeding efforts by various national and international agencies, yields for the similar to 40 million hectares of maize, the major food crop in sub-Saharan Africa, have stagnated at <2 tons/ha/year for the past decade, one-third the global average. Breeders have succeeded in breeding increased yield with a modicum of tolerance to some single-weed or pathogen stresses. There has been minimal adoption of these varieties because introgressing polygenic yield and tolerance traits into locally adapted material is very challenging. Multiple traits to deal with pests (weeds, pathogens, and insects) are needed for farmer acceptance, because African fields typically encounter multiple pest constraints. Also, maize has no inherent resistance to some of these pest constraints, rendering them intractable to traditional breeding. The proposed solution is to simultaneously engineer multiple traits into one genetic locus. The dominantly inherited multi-pest resistance trait single locus can be bred simply into locally adapted, elite high-yielding material, and would be valuable for farmers, vastly increasing maize yields, and allowing for more than regional maize sufficiency. (c) 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Pesticides, especially herbicides, have revolutionized agriculture by providing energy-efficient solutions for pest control that replaces labor-intensive cultivation methods. However, the widespread evolution of pesticide resistance poses a significant challenge to current agriculture. Most pesticides function by binding to specific pockets on target enzymes, enabling a single mutation to confer resistance. An alternative approach is the disruption of protein-protein interactions (PPI), thus for resistance to occur, it requires complementary mutations on both interacting partners. Despite extensive efforts, no herbicides with new modes of action have been commercialized for decades. Thus, we focused on the discovery and design of small molecule inhibitors that target the interface of the PPI complex of O-acetylserine sulfhydrylase (OASS) and serine acetyltransferase (SAT), key plant enzymes involved in the biosynthesis of the essential amino acid cysteine. Using in silico filtering techniques on a virtual library of 30 million small molecules, we identified initial hits capable of binding OASS and interfering with its interaction with a peptide derived from SAT. Subsequently, we conducted chemical optimizations to evaluate biophysical enzyme disruption, followed by cellular and in-planta activity in plants. These new compounds described herein can serve as promising starting points for further optimization as herbicides acting on a new mode of action.### Competing Interest StatementThe research was supported by funding of Projini AgChem Ltd. R.B.S, E.C, N.D and I.B are employees of Projini AgChem Ltd. J.G and M.G are consultants to Projini AgChem Ltd. Projini is the assignee of PCT patent WO 2023/06267 HERBICIDES AND USE THEREOF. Projini Ltd was funded by Migal, the Israeli innovation authority (IIA) and the trendlines-Bayer fund.

BACKGROUND: The widespread evolution of pesticide resistance poses a significant challenge to current agriculture, necessitating the discovery of molecules with new modes of action. Despite extensive efforts, no major molecules with new modes of action have been commercialized for decades. Most pesticides function by binding to specific pockets on target enzymes, enabling a single target site mutation to confer resistance. An alternative approach is the disruption of protein-protein interactions (PPI), which require complementary mutations on both interacting partners for resistance to occur. Thus, our aim is the discovery and design of small-molecule inhibitors that target the interface of the PPI complex of O-acetylserine sulfhydrylase (OASS) and serine acetyltransferase (SAT), key obligatory interacting plant enzymes involved in the biosynthesis of the amino acid cysteine. RESULTS: By employing in silico filtering techniques on a virtual library of 30 million small molecules, we identified initial hits capable of binding OASS and interfering with its interaction with a peptide derived from SAT with a half-maximal inhibitory concentration (IC50) of 34 mu m. Subsequently, we conducted molecular chemical optimizations, generating an early lead molecule (PJ4) with an IC50 value of 4 mu m. PJ4 successfully inhibited the germination of Arabidopsis thaliana seedlings and inhibited clover growth in a pre-emergence application at an effective concentration of 4.6 kg ha(-1). CONCLUSION: These new compounds described herein can serve as promising leads for further optimization as herbicides with a new mode-of-action. This technology can be used for discovering new modes of action chemicals inhibiting all pest groups. (c) 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

AbstractDuring the past 30 yr an impasse has developed in the discovery and commercialization of synthetic herbicides with new molecular targets and novel chemistries. Similarly, there has been little success with bioherbicides, both microbial and chemical. These bioherbicides are needed to combat fast-growing herbicide resistance and to fulfill the need for more environmentally and toxicologically safe herbicides. In response to this substantial and growing opportunity, numerous start-up companies are utilizing novel approaches to provide new tools for weed management. These diverse new tools broaden the scope of discovery, encompassing advanced computational, bioinformatic, and imaging platforms; plant genome–editing and targeted protein degradation technologies; and machine learning and artificial intelligence (AI)-based strategies. This review contains summaries of the presentations of 10 such companies that took part in a symposium held at the WSSA annual meeting in 2024. Four of the companies are developing microbial bioherbicides or natural product–based herbicides, and the other six are using advanced technologies, such as AI, to accelerate the discovery of herbicides with novel molecular target sites or to develop non-GMO, herbicide-resistant crops.

Despite biocontrol conceptually being a useful way to control specific pests, there are very few products that are used beyond the greenhouse level, into the field. Only if organisms meet four criteria (four pillars) will they be widely used in the field to replace or augment conventional agrichemicals. 1. The virulence of the biocontrol agent must be enhanced to overcome evolutionary barriers either by mixing with synergistic chemicals or with one or more organisms, and/or by mutagenic or transgenic enhancing of virulence of the biocontrol fungus; 2. Inoculum production must be cost-effective; many inocula are produced by expensive, labour-intensive solid-phase fermentation; 3. Inocula must be formulated both to have long shelf life of inocula as well as being formulated to establish on, and control the target pest. Usually spores are formulated, while chopped mycelia from liquid culture are cheaper to produce and are immediately active upon application; 4. After fulfilling these three criteria, the product must be biosafe: not produce mammalian toxins that affect users and consumers, and have a host range that does not include crops and beneficial organisms, and in most cases that it will not spread from application sites or have environmental residues beyond those needed to control the target pest. This article is protected by copyright. All rights reserved.

Societal Impact Statement Given the rapidly increasing drought and temperature stresses associated with climate change, innovative approaches for food security are imperative. One understudied opportunity is using feral crops—plants that have escaped and persisted without cultivation—as a source of genetic diversity, which could build resilience in domesticated conspecifics. In some cases, however, feral plants vigorously compete with crops as weeds, challenging food security. By bridging historically siloed ecological, agronomic, and evolutionary lines of inquiry into feral crops, there is the opportunity to improve food security and understand this relatively understudied anthropogenic phenomenon. Summary The phenomenon of feral crops, that is, free‐living populations that have established outside cultivation, is understudied. Some researchers focus on the negative consequences of domestication, whereas others assert that feral populations may serve as useful pools of genetic diversity for future crop improvement. Although research on feral crops and the process of feralization has advanced rapidly in the last two decades, generalizable insights have been limited by a lack of comparative research across crop species and other factors. To improve international coordination of research on this topic, we summarize the current state of feralization research and chart a course for future study by consolidating outstanding questions in the field. These questions, which emerged from the colloquium “Darwins' reversals: What we now know about Feralization and Crop Wild Relatives” at the BOTANY 2021 conference, fall into seven categories that span both basic and applied research: (1) definitions and drivers of ferality, (2) genetic architecture and pathway, (3) evolutionary history and biogeography, (4) agronomy and breeding, (5) fundamental and applied ecology, (6) collecting and conservation, and (7) taxonomy and best practices. These questions serve as a basis for ferality researchers to coordinate research in these areas, potentially resulting in major contributions to food security in the face of climate change.

Evolved resistance and regulatory deregistration have severely limited farmers' pesticide options. Many potential new pesticide target sites have been elucidated using targeted gene suppression and mutational tools, but few small molecules could be found that inhibit the target enzymes; the targets were considered 'undruggable'. Some organisms from all biological kingdoms use toxic peptides to ward off or kill enemies, and the agrochemical industry has used a few peptide analogs (glufosinate and bialophos) for field application. Conversely, pharmaceutical scientists have been using three-dimensional target protein structure to discover and synthesize short peptides that bind tightly to the surfaces of, and inhibit previously undruggable targets. New computational tools to quickly elucidate 3-D protein structure from amino acid sequence have just emerged. They replace crystallizing target proteins and performing X-ray crystallography to elucidate 3-D structure. These new tools allow prediction of peptides that will bind to the target proteins. They have further modified such peptides to enhance penetration, translocation and temperature stability. There is reason to assume that the same pioneering techniques can be used to develop peptide pesticides as well as pesticide synergists that act against undruggable targets and have excellent environmental and toxicological profiles. © 2022 Society of Chemical Industry.

For many years, the emphasis of industry discovery programs has been on finding new target sites of pesticides and finding pesticides that inhibit single targets. There had been an emphasis on genomics in finding single targets for potential pesticides. There is also the claim that registration of single target inhibiting pesticides is simpler if the mode of action is known. Conversely, if one looks at the evolution of resistance from an epidemiological perspective to ascertain which pesticides have been the most recalcitrant to evolutionary forces, it is those that have multiple target sites of action. Non-target-site resistances can evolve to multi-target-site inhibitors, but these resistances can often be overcome by structural modification of the pesticide. Industry has looked at pest-toxic natural products as pesticide leads, but seems to have abandoned those where they can find no single target of action. Perhaps nature has been intelligent and evolved many natural products that are synergistic multi-target-site inhibitors, and that is why natural compounds have been active for millennia? We should be learning from nature while combining new chemistry technologies with vast accrued databases and computer aided design allowing fragment-based discovery and scaffold hopping to produce multi-target site inhibitors instead of single target pesticides. © 2019 Society of Chemical Industry.

Pest Management ScienceVolume 74, Issue 4 p. 779-780 Editorial In Focus: Innovative crop protection for 21st century food security Jonathan Gressel, Jonathan Gressel Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot, IsraelSearch for more papers by this authorRobert Edwards, Robert Edwards School of Natural and Environmental Sciences, Newcastle University, Newcastle, Upon-Tyne NE1 7RU, UKSearch for more papers by this author Jonathan Gressel, Jonathan Gressel Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot, IsraelSearch for more papers by this authorRobert Edwards, Robert Edwards School of Natural and Environmental Sciences, Newcastle University, Newcastle, Upon-Tyne NE1 7RU, UKSearch for more papers by this author First published: 28 February 2018 https://doi.org/10.1002/ps.4868Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume74, Issue4April 2018Pages 779-780 RelatedInformation

There is often strong public dissent to innovations, typically fanned by those who lose out economically, but the reasons they promulgate are not economic and are targeted to public emotions. Agriculture has some problems that have been intractable to present technologies and we have no choice but to utilize new technologies to overcome them. These include developing new herbicides that affect multiple targets, new selective synergists and safeners, transgenic herbicide resistant plants that will not have the transgenes expressed in related weeds, using transposons or gene drives to disseminate deleterious genes in weeds, sterile pollen, enhanced-virulence biocontrol agents with sustaining formulations. These might be workable for multiple resistant Amaranthus and Echinochloa species, parasitic weeds, Phalaris in wheat as well as weedy rice in rice. Per force, most of the innovations must originate in the public sector, by weed scientists who have a broad training in basic sciences, in collaboration with experts from other fields.

Liver-affecting, carcinogenic aflatoxins produced by Aspergillus spp. are a major problem, especially in the humid developing world where storage conditions are often optimal for the fungi. Peanuts and maize have been transformed with RNAi constructs targeting Aspergillus flavus polyketide-synthase, an early key enzyme in aflatoxin biosynthesis. Aflatoxin biosynthesis was suppressed in developing immature grain, less so in late maturing grain, and it is doubtful that the technology will be effective in near dry mature grain. The infected grain was still mouldy. As Aspergillus that infects grain preharvest can continue to grow and produce aflatoxin in poorly stored grain, and grain storage insects vector further infections, this technology seems to have little potential utility in the humid tropics. The biotechnological approaches of RNAi directly targeting Aspergillus, coupled with transgenic insecticidal proteins should be far more effective. These biotechnological approaches can be used in tandem with the RNAi against polyketide-synthase, as well as with irradiation, biocontrol and better grain drying and hermetic dry storage in a controlled atmosphere. © 2017 Society of Chemical Industry.

Microbiome organisms can degrade environmental xenobiotics including pesticides, conferring resistance to most types of pests. Some cases of pesticide resistance in insects, nematodes and weeds are now documented to be due to microbiome detoxification, and is a demonstrated possibility with rodents. Some cases of metabolic resistance may have been misattributed to pest metabolism, and not to organisms in the microbiome, because few researchers use axenic pests in studying pesticide metabolism. Instances of microbiomes evolving pesticide resistance contributing to resistance of their hosts may become more common due the erratic nature of climate change, as microbiome populations typically increase and evolve faster in stressful conditions. Conversely, microbiome organisms can be engineered to provide crops and beneficial insects with needed resistance to herbicides and insecticides, respectively, but there has not been sufficient efficacy to achieve commercial products useful at the field level, even with genetically engineered microbiome organisms. © 2017 Society of Chemical Industry.

Resistance has evolved to single transgenic traits engineered into crops for arthropod and herbicide resistances, and can be expected to evolve to the more recently introduced pathogen resistances. Combining transgenes against the same target pest is being promoted as the solution to the problem. This solution will work if used pre-emptively, but where resistance has evolved to one member of a stack, resistance should easily evolve for the second gene in most cases. We propose and elaborate criteria that could be used to evaluate the value of stacked traits for pest resistance management. Stacked partners must: target the same pest species; be in a tandem construct to preclude segregation; be synchronously expressed in the same tissues; have similar tissue persistence; target pest species that are still susceptible to at least two stacked partners. Additionally, transgene products must not be degraded in the same manner, and there should be a lack of cross-resistance to stacked transgenes or to their products. With stacked herbicide resistance transgenes, both herbicides must be used and have the same persistence. If these criteria are followed, and integrated with other pest management practices, resistance may be considerably delayed. © 2016 Society of Chemical Industry.