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Naroči gradivo
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Perspective: present pesticide discovery paradigms promote the evolution of resistance – learn from nature and prioritize multi‐target site inhibitor design
Gressel, Jonathan
Pest management science,
February 2020, 2020-Feb, 2020-02-00, 20200201, Letnik:
76, Številka:
2
Journal Article
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
Pesticide discovery paradigm must be changed towards multi‐target‐site inhibitors to delay resistance.
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The naming of the blue UV photoreceptor “cryptochrome”: From despised pun to ubiquitously found chromophore(s) controlling multiple functions
Gressel, Jonathan
Photochemistry and photobiology,
May/June 2024, 2024 May-Jun, 2024-05-00, 20240501, Letnik:
100, Številka:
3
Journal Article
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.
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Four pillars are required to support a successful biocontrol fungus
Gressel, Jonathan
Pest management science,
January 2024, 2024-Jan, 2024-01-00, 20240101, Letnik:
80, Številka:
1
Journal Article
Despite biocontrol conceptually being a useful way to control specific pests, there are very few products that are used beyond the glasshouse 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. (i) 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. (ii) Inoculum production must be cost‐effective; many inocula are produced by expensive, labour‐intensive solid‐phase fermentation. (iii) 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. (iv) 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. © 2023 Society of Chemical Industry.
Four criteria (pillars) must be met to have a commercially viable biocontrol fungus: (i) enhanced virulence; (ii) inexpensive inocula; (iii) appropriate formulation; (iv) meet biosafety requirements.
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Microbiome facilitated pest resistance: potential problems and uses
Gressel, Jonathan
Pest management science,
March 2018, 2018-Mar, 2018-03-00, 20180301, Letnik:
74, Številka:
3
Journal Article
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
Microbiome detoxification of herbicides and insecticides is being demonstrated as a form of resistance. Engineered microbiomes can protect crops and beneficial insects from pesticides.
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Transgenics are imperative for biofuel crops
Gressel, Jonathan
Plant science (Limerick),
03/2008, Letnik:
174, Številka:
3
Journal Article
Petroleum dependency is a challenge that can potentially be partly offset by agricultural production of biofuels, while decreasing net, non-renewable carbon dioxide output. Plants have not been ...
domesticated for modern biofuel production, and the quickest, most efficient, and often, the only way to convert plants to biofuel feedstocks is biotechnologically. First generation biofuel feedstock sources: sugarcane and cereal grains to produce bioethanol and biobutanol and oilseeds to produce biodiesel compete directly with needs for world food security. The heavy use of oilseed rape releases quantities of methyl bromide to the atmosphere, which can be prevented by gene suppression. Second generation bioethanolic/biobutanolic biofuels will come from cultivated lignocellulosic crops or straw wastes. These presently require heat and acid to remove lignin, which could be partially replaced by transgenically reducing or modifying lignin content and upregulating cellulose biosynthesis. Non-precipitable silicon emissions from burning could be reduced by transgenically modulating silicon content. The shrubby
Jatropha and castor beans should have highly toxic protein components transgenically removed from their meal, cancer potentiating diterpenes removed from the oils, and allergens from the pollen, before extensive cultivation. Algae and cyanobacteria for third generation biodiesel need transgenic manipulation to deal with “weeds”, light penetration, photoinhibition, carbon assimilation, etc. The possibilities of producing fourth generation biohydrogen and bioelectricity using photosynthetic mechanisms are being explored. There seem to be no health or environmental impact study requirements when the undomesticated biofuel crops are grown, yet there are illogically stringent requirements should they transgenically be rendered less toxic and more efficient as biofuel crops.
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Perspective: It is time to consider new ways to attack unpesticidable (undruggable) target sites by designing peptide pesticides
Gressel, Jonathan
Pest management science,
June 2022, Letnik:
78, Številka:
6
Journal Article
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.
Genomic techniques have elucidated potential pesticide targets, but no small molecules tested inhibited the targets; ‘non‐druggable’ targets. Pharma has successfully designed peptides that bind to the surface of previously undruggable targets, abolishing activity; a technology that should work to develop pesticides attacking new targets sites.
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Low pesticide rates may hasten the evolution of resistance by increasing mutation frequencies
Gressel, Jonathan
Pest management science,
March 2011, Letnik:
67, Številka:
3
Journal Article
At very low pesticide rates, a certain low proportion of pests may receive a sublethal dose, are highly stressed by the pesticide and yet survive. Stress is a general enhancer of mutation rates. ...
Thus, the survivors are likely to have more than normal mutations, which might include mutations leading to pesticide resistance, both for multifactorial (polygenic, gene amplification, sequential allelic mutations) and for major gene resistance. Management strategies should consider how to eliminate the subpopulation of pests with the high mutation rates, but the best strategy is probably to avoid too low application rates of pesticides from the outset. Copyright
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Dealing with transgene flow of crop protection traits from crops to their relatives
Gressel, Jonathan
Pest management science,
20/May , Letnik:
71, Številka:
5
Journal Article
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
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