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tenuazonic acid
Toxins · 2025 ·Vol. 17 ·期 4 ·181 · IF 4

Toxin Production by Alternaria alternata in Black Spot Disease of Chrysanthemum morifolium ‘Fubai’: Accumulation of Altenuene and Tenuazonic Acid in Flowers

Qingling Zhan,Lina Liu,Wenjie Li,Jingshan Lu,Jiafu Jiang,Fadi Chen,Ye Liu,Zhiyong Guan

Alternariaspecies produce diverse secondary metabolites that act as critical virulence factors during plant pathogenesis. In cultivation areas ofChrysanthemum morifolium‘Fubai’—a key cultivar for herbal tea—black spot disease caused byA. alternatamanifests as necrotic leaf lesions progressing to wilting. Despite this disease’s economic impact, information on its associated toxins is limited, and the types of toxins produced by the black spot pathogen ofChrysanthemum morifolium‘Fubai’ in particular remain unclear. Furthermore, whether toxins are present in the flowers when the leaves show symptoms is uncertain, but their inflorescence is not visibly infected. Using two previously characterizedA. alternatastrains (F16/F20) isolated from ‘Fubai’ in earlier studies, we demonstrated the concomitant production of altenuene (ALT) and tenuazonic acid (TeA) in both strains, with strain-specific yield variations (F20 TeA: 342.16 µg/mL vs. F16: 21.84 µg/mL; ALT: 0.28 µg/mL vs. 0.90 µg/mL). Time-course monitoring revealed coordinated accumulation of both toxins in inoculated petals, reaching 18.07 μg/g ALT and 2.59 µg/g TeA by day 9. Notably, these two toxins were detected only in flower samples from black spot-infected plants, and their concentrations correlated closely with disease severity in the leaves. Moreover, although the inflorescences did not display symptoms, both fresh and dried flowers retained detectable toxin levels. We established a technical system for the extraction and quantitative detection of the toxins ALT and TeA produced by the black spot pathogen in tea chrysanthemum. This work provides the first confirmation of ALT/TeA co-contamination inChrysanthemum morifolium‘Fubai’, revealing substantial dietary exposure risks through tea consumption. Our findings suggest that, from a food safety risk reduction perspective, integrated management strategies should be developed to minimize toxin contamination in tea chrysanthemum, including improved disease prevention measures and potential regulatory considerations.

CAS / MDL: 64-18-6
研究领域: 植物病理学 · 食品安全 · 次生代谢产物研究
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Analytical Methods · 2021 ·Vol. 13 ·期 15 ·1795-1802 · IF 2.896

Development of a chemiluminescence immunoassay for detection of tenuazonic acid mycotoxin in fruit juices with a specific camel polyclonal antibody

Feng Wang,De-Bin Wan,Yu-Dong Shen,Yuan-Xin Tian,Zhi-Li Xiao,Zhen-Lin Xu,Jin-Yi Yang,Yuan-Ming Sun,Bruce D. Hammock,Hong Wang

The natural mycotoxin tenuazonic acid (TeA) in foods is identified as the most toxic mycotoxin among the over 70 kinds of secondary toxic metabolites produced by Alternaria alternata. Some hapten–antibody-mediated immunoassays have been developed for TeA detection in food samples, but these methods show unsatisfactory sensitivity and specificity. In this study, a rationally designed hapten for TeA mycotoxin generated with computer-assisted modeling was prepared to produce a highly specific camel polyclonal antibody, and an indirect competitive chemiluminescence enzyme immunoassay (icCLEIA) was established with a limit of detection of 0.2 ng mL−1 under optimized conditions. The cross-reactivity results showed that several analogs and some common mycotoxins had negligible recognition by the anti-TeA polyclonal antibody. The average recoveries spiked in fruit juices were determined to be 92.7% with an acceptable coefficient of variation, and good correlations between icCLEIA and liquid chromatography tandem mass spectrometry (LC-MS/MS) results were obtained in spiked samples. This developed icCLEIA for TeA detection with significantly improved sensitivity and satisfactory specificity is a promising alternative for environmental monitoring and food safety.

CAS / MDL: 641-38-3 51481-10-8
研究领域: 食品科学 · 免疫学
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PEST MANAGEMENT SCIENCE · 2024 · IF 3.8

Dipicolinic acid reduces Epicoccum sorghinum symptoms on maize and inhibits tenuazonic acid biosynthesis

Xin-Yu Ji,Bing-Yi Wang,Yi-Feng Zhang,Yu-Jing Zhang,Ya-Jie Lai,Yang Yang,Xiang-Chen Wang,Su-Yan Wang,Pedro Laborda,Xin-Chi Shi

BACKGROUND Epicoccum sorghinum is a pathogenic fungus that causes leaf spot in a wide range of plants, including maize, and synthesizes the mycotoxin tenuazonic acid (TEA), which is carcinogenic. Despite the relevant economic and yield losses caused by E. sorghinum worldwide, methods for the control of this pathogen are lacking. RESULTS In this work, the efficacy of Bacillus -produced dipicolinic acid (DPA) for control of E. sorghinum was evaluated using in vitro and in vivo assays, and compared with the efficacy of three commercial fungicides, including carbendazim, prochloraz, and thiram. DPA inhibited E. sorghinum mycelial growth, and conidia germination, and produced important alterations in E. sorghinum hyphae. Interestingly, 10 mM DPA reduced TEA biosynthesis by 86.6%. Although DPA rapidly degraded on maize leaves, 10 mM DPA showed higher preventive (67.4% lesion length inhibition) and inhibitory (89.5% lesion length inhibition) efficacies for the control of E. sorghinum on maize leaves compared to the commercial fungicides. CONCLUSIONS Collectively, this study presents the first method for the control of E. sorghinum on maize and demonstrates that DPA application is a suitable approach to inhibit E. sorghinum symptoms in plants and TEA biosynthesis. © 2024 Society of Chemical Industry.

CAS / MDL: 67747-09-5
研究领域: 植物病理学 · 农业科学 · 毒理学
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Journal of Advanced Research · 2021 · IF 10.479

Structure-based ligand design and discovery of novel tenuazonic acid derivatives with high herbicidal activity

He Wang,Qin Yao,Yanjing Guo,Qian Zhang,Zhongchang Wang,Reto Jörg Strasser,Bernal E. Valverde,Shiguo Chen,Sheng Qiang,Hazem M. Kalaji

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 B 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.

CAS / MDL: 811-98-3 75-76-3
研究领域: 植物学 · 农药科学 · 计算生物学
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FOOD CONTROL · 2022 · IF 6.652

Nanobodies for accurate recognition of iso-tenuazonic acid and development of sensitive immunoassay for contaminant detection in foods

Feng Wang,Yuan-Yuan Yang,De-Bin Wan,Jia-Dong Li,Yi-Fan Liang,Zhen-Feng Li,Yu-Dong Shen,Zhen-Lin Xu,Jin-Yi Yang,Hong Wang,Jan Gettemans,Bruce D. Hammock,Yuan-Ming Sun

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 Alternaria 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.

研究领域: 食品安全 · 免疫学 · 分析化学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2021 · IF 5.279

Enhanced Non-Toxic Immunodetection of Alternaria Mycotoxin Tenuazonic Acid Based on Ferritin-Displayed Anti-Idiotypic Nanobody-Nanoluciferase Multimers

Feng Wang,Zhen-Feng Li,De-Bin Wan,Natalia Vasylieva,Yu-Dong Shen,Zhen-Lin Xu,Jin-Yi Yang,Jan Gettemans,Hong Wang,Bruce D. Hammock,Yuan-Ming Sun

The non-toxic immunoassay for mycotoxins is being paid more attention due to its advantages of higher safety and cost savings by using anti-idiotype antibodies to substitute toxins. In this study, with tenuazonic acid (TeA), a kind of highly toxic Alternaria mycotoxin as the target, an enhanced non-toxic immunoassay was developed based on the ferritin-displayed anti-idiotypic nanobody-nanoluciferase multimers. First, three specific β-type anti-idiotype nanobodies (AId-Nbs) bearing the internal image of TeA mycotoxin were selected from an immune phage display library. Then, the AId-Nb 2D with the best performance was exploited to generate a nanoluciferase (Nluc)-functionalized fusion monomer, by which a one-step non-toxic immunodetection format for TeA was established and proven to be effective. To further improve the affinity of the monomer, a ferritin display strategy was used to prepare 2D-Nluc fusion multimers. Finally, an enhanced bioluminescent enzyme immunoassay (BLEIA) was established in which the half maximal inhibitory concentration (IC50) for TeA was 6.5 ng/mL with a 10.5-fold improvement of the 2D-based enzyme-linked immunosorbent assay (ELISA). The proposed assay exhibited high selectivities and good recoveries of 80.0–95.2%. The generated AId-Nb and ferritin-displayed AId-Nb-Nluc multimers were successfully extended to the application of TeA in food samples. This study brings a new strategy for production of multivalent AId-Nbs and non-toxic immunoassays for trace toxic contaminants.

CAS / MDL: 51481-10-8 17924-92-4
研究领域: 食品安全 · 生物化学 · 免疫学
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Agriculture-Basel · 2022 ·Vol. 12 ·期 2 ·204 · IF 3.408

A High Sensitivity Electrochemical Immunosensor Based on Monoclonal Antibody Coupled Flower-Shaped Nano-ZnO for Detection of Tenuazonic Acid

Chi Zhang,Congcong Du,Wei Liu,Ting Guo,Ying Zhou,Hongyuan Zhou,Yuhao Zhang,Xiaozhu Liu,Liang Ma

In this paper, an electrochemical biosensor was established for the high-sensitivity detection of Tenuazonic acid (TeA) in fruits based on the enrichment of flower-shaped nano-ZnO and the specific recognition of immune response. Herein flower-shaped nano-ZnO (ZnO NFs) with a hexagonal wurtzite structure and diameter of 700–800 nm were demonstrated to have the optimal specific surface area and outstanding conductivity, compared with different morphology, sizes, and crystal structures of nano-ZnO. Second, the ZnO NFs were used as carriers for efficiently immobilizing monoclonal antibodies to obtain antibody bioconjugates, which were anchored on the 2-mercaptobenzoic acid-modified gold electrode by amide reaction. In the presence of TeA, the monoclonal antibody could specifically recognize and bind to it, resulting in a decrease in electron transfer ability on the gold electrode surface. Finally, the electrochemical biosensor showed a range from 5 × 10−5μg/mL to 5 × 10−1μg/mL with a detection limit of 1.14 × 10−5μg/mL. Furthermore, it exhibited high selectivity for TeA among other analogs, such as Altenuene (ALT) and Alternariol (AOH). Notably, the proposed strategy could be employed to monitor TeA in tomato and citrus, showing potential application prospects in practical application and commercial value.

研究领域: 食品科学 · 分析化学 · 免疫学
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ANALYTICAL CHEMISTRY · 2020 · IF 6.785

Chemiluminescent Enzyme Immunoassay and Bioluminescent Enzyme Immunoassay for Tenuazonic Acid Mycotoxin by Exploitation of Nanobody and Nanobody–Nanoluciferase Fusion

Feng Wang,Zhen-Feng Li,Yuan-Yuan Yang,De-Bin Wan,Natalia Vasylieva,Yu-Qi Zhang,Jun Cai,Hong Wang,Yu-Dong Shen,Zhen-Lin Xu,Bruce D. Hammock

The isolation of nanobodies (Nbs) from phage display libraries is an increasingly effective approach for the generation of new biorecognition elements, which can be used to develop immunoassays. In this study, highly specific Nbs against the Alternaria mycotoxin tenuazonic acid (TeA) were isolated from an immune nanobody phage display library using a stringent biopanning strategy. The obtained Nbs were characterized by classical enzyme-linked immunosorbent assay (ELISA), and the best one Nb-3F9 was fused with nanoluciferase to prepare an advanced bifunctional fusion named nanobody–nanoluciferase (Nb–Nluc). In order to improve the sensitivity and reduce the assay time, two different kinds of luminescent strategies including chemiluminescent enzyme immunoassay (CLEIA) and bioluminescent enzyme immunoassay (BLEIA) were established, respectively, on the basis of the single Nb and the fusion protein Nb–Nluc for TeA detection. The two-step CLEIA was developed on the basis of the same nanobody as ELISA, only with simple substrate replacement from 3,3′,5,5′-tetramethylbenzidine (TMB) to luminol. In contrast with CLEIA, the novel BLEIA was conducted in one-step new strategy on the basis of Nb–Nluc and bioluminescent substrate coelenterazine-h (CTZ-h). Their half maximal inhibitory concentration (IC50) values were similar to 8.6 ng/mL for CLEIA and 9.3 ng/mL for BLEIA, which was a 6-fold improvement in sensitivity compared with that of ELISA (IC50 of 54.8 ng/mL). Both of the two assays provided satisfactory recoveries ranging from 80.1%–113.5% in real samples, which showed better selectivity for TeA analogues and other common mycotoxins. These results suggested that Nbs and Nb–Nluc could be used as useful reagents for immunodetection and that the developed CLEIA/BLEIA have great potential for TeA analysis.

研究领域: 食品科学 · 毒理学 · 分析化学 · 免疫学
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