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Journal of Advanced Research Sep 2022Computer-aided design has become an important tool to develop novel pesticides based on natural lead compounds. Tenuazonic acid (TeA), a typical representative of the...
INTRODUCTION
Computer-aided design has become an important tool to develop novel pesticides based on natural lead compounds. Tenuazonic acid (TeA), a typical representative of the natural tetramic acid family, was patented as a potential bioherbicide. However, its herbicidal efficacy is still not up to the ideal standard of commercial products.
OBJECTIVES
We aim to find new TeA's derivatives with improved potency.
METHODS
Molecular docking was used to build ligand-acceptor interaction models, design and screen new derivatives. Phytotoxicity, oxygen evolution rate, chlorophyll fluorescence and herbicidal efficacy were determined to estimate biological activity of compounds.
RESULTS
With the aid of a constructed molecular model of natural lead molecule TeA binding to the Q site in Arabidopsis D1 protein, a series of derivatives differing in the alkyl side chain were designed and ranked according to free energies. All compounds are stabilized by hydrogen bonding interactions between their carbonyl oxygen O2 and D1-Gly256 residue; moreover, hydrogen bond distance is the most important factor for maintaining high binding affinity. Among 54 newly designed derivatives, D6, D13 and D27 with better affinities than TeA were screened out and synthesized to evaluate their photosynthetic inhibitory activity and herbicidal efficacy. Analysis of structure-activity relationship indicated that D6 and D13 with sec-pentyl and sec-hexyl side chains, respectively, were about twice more inhibitory of PSII activity and effective as herbicide than TeA with a sec-butyl side chain.
CONCLUSION
D6 and D13 are promising compounds to develop TeA-derived novel PSII herbicides with superior performance.
Topics: Herbicides; Ligands; Molecular Docking Simulation; Oxygen; Tenuazonic Acid
PubMed: 36100332
DOI: 10.1016/j.jare.2021.12.001 -
Food Control Jun 2022The accurate analysis of chemical isomers plays an important role in the study of their different toxic effects and targeted detection of pollutant isomers in foods. The...
The accurate analysis of chemical isomers plays an important role in the study of their different toxic effects and targeted detection of pollutant isomers in foods. The mycotoxins tenuazonic acid (TeA) and iso-tenuazonic acid (ITeA) are two isomer mycotoxins with the lack of single analysis methods due to the similar structures. Antibody-based immunoassays exhibit high sensitivity and superior application in isomer-specific determination. Previously, various kinds of antibodies for TeA have been prepared in our group. Herein, highly specific nanobodies (Nbs) against ITeA mycotoxin were selected from immune nanobody phage display library, and one of Nbs, namely Nb(B3G3) exhibited excellent affinity, thermal stability as well as organic solvent tolerance. By molecular simulation and docking technology, it was found that stronger interaction between Nb(B3G3) and ITeA lead to higher affinity than that for its isomer TeA. Furthermore, a sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) was established with a limit of detection (LOD) of 0.09 ng/mL for ITeA mycotoxin. The recovery rate of ITeA in spiked samples was analyzed with 84.8%-89.5% for rice, 78.3%-96.3% for flour, and 79.5%-90.7% for bread. A conventional LC-MS/MS method was used to evaluate the accuracy of this proposed icELISA, which showed a satisfactory consistent correlation. Since the convenient strategy for nanobody generation by phage display technology, this study provide new biorecognition elements and sensitive immunoassay for analysis of ITeA in foods.
PubMed: 35989708
DOI: 10.1016/j.foodcont.2022.108835 -
Frontiers in Bioengineering and... 2022Tenuazonic acid (TA) is a highly toxic mycotoxin mainly generated by the fungi of genus and widely contaminates agricultural by-products. Given the threat of TA to...
Tenuazonic acid (TA) is a highly toxic mycotoxin mainly generated by the fungi of genus and widely contaminates agricultural by-products. Given the threat of TA to food-security, it is very important to develop rapid and sensitive detection methods for TA monitoring. In this study, gold nano-particles (AuNP) with average diameter near 17.25 nm were prepared, and the developed AuNP-based strip has an assay time of 15 min with visual limit of detection (LOD) of 12.5 ng/ml and threshold of 100 ng/ml. To further improve sensitivity, multi-branched gold nano-flowers (AuNF) with average diameter near 50 nm were prepared and characterized by UV-VIS and TEM, and the established AuNF-based strip has visual LOD of 0.78 ng/ml and threshold of 50 ng/ml within 15 min. Both assays were applied to determine TA in apple juice and tomato ketchup, and the results were consistent with that of UHPLC-MS/MS. Thus, these assays could be applied for rapid determination of trace TA in real samples.
PubMed: 36277402
DOI: 10.3389/fbioe.2022.1021758 -
Journal of Agricultural and Food... Aug 2017Modern analytical techniques can determine a multitude of fungal metabolites contaminating food and feed. In addition to known mycotoxins, for which maximum levels in... (Review)
Review
Modern analytical techniques can determine a multitude of fungal metabolites contaminating food and feed. In addition to known mycotoxins, for which maximum levels in food are enforced, also currently unregulated, so-called "emerging mycotoxins" were shown to occur frequently in agricultural products. The aim of this review is to critically discuss the relevance of selected emerging mycotoxins to food and feed safety. Acute and chronic toxicity as well as occurrence data are presented for enniatins, beauvericin, moniliformin, fusaproliferin, fusaric acid, culmorin, butenolide, sterigmatocystin, emodin, mycophenolic acid, alternariol, alternariol monomethyl ether, and tenuazonic acid. By far not all of the detected compounds are toxicologically relevant at their naturally occurring levels and are therefore of little or no health concern to consumers. Still, gaps in knowledge have been identified for several compounds. These gaps should be closed by the scientific community in the coming years to allow a proper risk assessment.
Topics: Animals; Crops, Agricultural; Food Contamination; Food Safety; Fungi; Humans; Mycotoxins
PubMed: 27599910
DOI: 10.1021/acs.jafc.6b03413 -
Molecular Plant-microbe Interactions :... May 2022Taking tenuazonic acid (TeA) synthetase 1 (TAS1) in as a reference, the homolog 1 was first anchored in via de novo sequencing. Subsequently, , as a major facilitator...
Taking tenuazonic acid (TeA) synthetase 1 (TAS1) in as a reference, the homolog 1 was first anchored in via de novo sequencing. Subsequently, , as a major facilitator superfamily (MFS) protein-encoding gene in the adjacent upstream region, was followed with interest. As hypothesized, AaTAS1 is required for TeA biosynthesis, while AaMFS1 is an efflux pump for the transmembrane transport of TeA. Comparatively, the TeA yield of Δ and Δ dropped significantly compared with that of the wild-type strain. Specifically, the A domain of AaTAS1 catalyzed the start of TeA biosynthesis in vitro. Simultaneously, the pathogenicity of Δ was also significantly decreased. Transcriptome analysis confirmed the abovementioned consistency between the TeA-producing phenotypes and related gene expression. Moreover, the proteins AaTAS1 and AaMFS1 were found present in the cytoplasm, plasma membrane, and intracellular membrane system, respectively, by fluorescence localization. Namely, AaTAS1 was responsible for the biosynthesis of TeA, and AaMFS1 was responsible for the efflux transport of TeA. Certainly, indirectly regulated the expression of through the level of synthetic TeA. Overall, data on the novel 1 and genes mainly contribute to theoretical advances in mycotoxin biosynthesis and the pathogenicity of phytopathogens to agricultural foods.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Topics: Alternaria; Mycotoxins; Tenuazonic Acid; Virulence
PubMed: 35175146
DOI: 10.1094/MPMI-12-21-0300-R -
Frontiers in Microbiology 2023This study was designed to assess the protective role of cinnamaldehyde (Cin) against the synergistic effect of tenuazonic acid (TeA) and Freund's adjuvant on different...
INTRODUCTION
This study was designed to assess the protective role of cinnamaldehyde (Cin) against the synergistic effect of tenuazonic acid (TeA) and Freund's adjuvant on different organs of Swiss albino mice.
METHODS
TeA was administered singly and in combination with Freund's adjuvant intra-peritoneally. The mice were divided into control (vehicle treated), mycotoxicosis-induced (MI) groups, and treatment groups. The route of administration of TeA was intra-peritoneal. The treatment group (FAICT) received Cin orally as a protective agent against TeA-induced mycotoxicosis. The effects on performance, differential leukocyte counts (DLC), and pathological measurements in eight organs (liver, lungs, kidney, spleen, stomach, heart, brain, and testis) were taken into consideration.
RESULTS
The body weight and feed consumption decreased significantly in the MI groups, which were reversed in the FAICT group. The necropsy observations revealed an increase in the relative organ-to-body weight percentage in the MI groups, which was restored to normal in the FAICT group. Freund's adjuvant enhanced the effects of TeA on DLC. The antioxidant enzymes SOD and CAT decreased, while MDA increased in the MI groups. Caspase-3 activity was reduced in all organs and remained stable in the treatment group. TeA elevated the ALT concentration in the liver and kidneys and the AST in the liver, kidney, heart, and brain tissues. The oxidative stress induced by TeA in the MI groups was ameliorated in the treatment group. Histopathological observations consisted of NASH, pulmonary oedema and fibrosis, renal crystals and inflammation, splenic hyperplasia, gastric ulceration and cyst, cerebral axonopathy, testicular hyperplasia, and vacuolation in the MI groups. However, no such pathology was recorded in the treatment group.
DISCUSSIONS
Thus, it can be concluded that the toxicity of TeA was found to be enhanced when combined with Freund's adjuvant. However, Cin exhibited promising protective effects against TeA + Freund's adjuvant toxicity and reverted the pathological alterations caused by them. Additionally, this study emphasizes Freund's adjuvant's ability to increase mycotoxicity rather than just acting as an immunopotentiator.
PubMed: 37426034
DOI: 10.3389/fmicb.2023.1159881 -
Frontiers in Microbiology 2022Alternariol (AOH), alternariol monomethyl-ether (AME), and tenuazonic acid (TeA) are major mycotoxins produced by fungi of the genus and are common contaminants of food...
Alternariol (AOH), alternariol monomethyl-ether (AME), and tenuazonic acid (TeA) are major mycotoxins produced by fungi of the genus and are common contaminants of food products such as fruits, vegetables, cereals and grains. mycotoxins are known to cause relevant economic losses and to have a negative impact on human and animal health. EFSA stated in its scientific opinion that data on the toxicity of mycotoxins in humans and livestock are generally lacking, precluding proper hazard characterization. This study aimed to fill some knowledge gaps by studying the cytotoxicity toward human intestinal epithelial cells (Caco-2) and hepatocytes (HepG2). Cytotoxic properties were assessed by flow cytometric analyses of remaining viable cells (i.e., propidium iodide negative) after mycotoxin exposure for 24-48 h versus solvent control. Treatment of cells with single doses of AOH, AME, and TeA resulted in a dose-dependent loss of cell viability for both cell lines. Half maximal effective concentrations (EC) of the different mycotoxins were comparable for the two cell lines. On HepG2 cells, EC values varying between 8 and 16, 4 and 5, and 40 and 95 μg/mL were calculated for AOH, AME, and TeA, respectively. On Caco-2 cells, EC values of 19 μg/mL and varying between 6 and 23, and 60 and 90 μg/mL were calculated for AOH, AME, and TeA, respectively. A general relative cytotoxicity ranking of about 1 = 1 >>> 3 was obtained for AOH, AME, and TeA, respectively. Treatment of both cell lines with combined binary and ternary mixtures of AOH, AME, and TeA in a 1:1:3 ratio, also showed a dose-dependent decrease in cell viability. For both cell lines, the binary combination of especially AME and TeA (1:3 ratio) but also of AOH and AME (1:1 ratio) significantly increased the cytotoxicity compared to the single compound toxicity, although mainly at the highest concentrations tested. The ternary combinations of AOH, AME, and TeA induced only a slight increase in cytotoxicity compared to the single mycotoxins, again at the highest concentrations tested.
PubMed: 35531275
DOI: 10.3389/fmicb.2022.849243 -
Foods (Basel, Switzerland) Apr 2024Among microorganisms found in food, fungi stand out because they are adaptable and competitive in a large range of water activities, temperatures, pHs, humidities and... (Review)
Review
Among microorganisms found in food, fungi stand out because they are adaptable and competitive in a large range of water activities, temperatures, pHs, humidities and substrate types. Besides sporulating, some species are toxigenic and produce toxic metabolites, mycotoxins, under adverse biotic and abiotic variables. Microorganisms are inactivated along the food chain, but mycotoxins have stable structures and remain in ready-to-eat food. The most prevalent mycotoxins in food, which are aflatoxins, fumonisins, ochratoxin A, patulin, tenuazonic acid, trichothecenes and zearalenone, have maximum tolerable limits (MTLs) defined as ppb and ppt by official organizations. The chronic and acute toxicities of mycotoxins and their stability are different in a chemical family. This critical review aims to discuss promising scientific research that successfully mitigated levels of mycotoxins and focus the results of our research group on this issue. It highlights the application of natural antifungal compounds, combinations of management, processing parameters and emergent technologies, and their role in reducing the levels and bioaccessibility. Despite good crop management and processing practices, total decontamination is almost impossible. Experimental evidence has shown that exposure to mycotoxins may be mitigated. However, multidisciplinary efforts need to be made to improve the applicability of successful techniques in the food supply chain to avoid mycotoxins' impact on global food insecurity.
PubMed: 38611416
DOI: 10.3390/foods13071112 -
Biomolecules Jan 2021Alzheimer's disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural...
Alzheimer's disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1-5), including tenuazonic-donepezil (TA-DNP) hybrids (4 and 5) due to the clinical importance of the anti-AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi-functional anti-neurodegenerative drugs, as exemplified by hybrid 5, a promising non-cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH-SY5Y human neuroblastoma cells.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Cell Line, Tumor; Cell Survival; Cholinesterase Inhibitors; Donepezil; Free Radical Scavengers; Humans; Hydrogen-Ion Concentration; Metals; Molecular Docking Simulation; Neuroprotection; Neuroprotective Agents; Protein Aggregates; Spectrophotometry; Tenuazonic Acid
PubMed: 33467709
DOI: 10.3390/biom11010111 -
Toxins Jul 2017Emerging and mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited.... (Review)
Review
Emerging and mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range), higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well.
Topics: Alternaria; Animals; Cyclobutanes; Depsipeptides; Food Contamination; Fusarium; Humans; Mycotoxins
PubMed: 28718805
DOI: 10.3390/toxins9070228