Cytochrome P450 monooxygenases are crucial for insect detoxification of xenobiotics. Here, we investigate the function of CYP6AQ1 from Apis cerana cerana (AccCYP6AQ1) in response to pesticide and heavy metal stress. This study reveals that AccCYP6AQ1 is significantly induced by pyrethroid insecticides. In vitro assays demonstrate that the encoded protein directly metabolizes cypermethrin and deltamethrin. Furthermore, through RNAi-mediated silencing, we find that AccCYP6AQ1 also mitigates cadmium- and mercury-induced toxicity. These results indicate that AccCYP6AQ1 participates in a multifunctional detoxification pathway, providing protection against both pesticides and heavy metals. Our results suggest that AccCYP6AQ1 is part of a broader detoxification network, likely representing an ecological adaptation of honey bees to complex chemical mixtures in agricultural environments.
{"title":"Metabolic Assays and RNAi-Based Functional Characterization of the P450 Gene CYP6AQ1 under Environmental Stress in Apis cerana cerana.","authors":"Wen-Feng Chen,Lin Xu,Hui-Xian Sun,Yu-Lin Xu,Shuang-Xiang Li,Hao-Bo Li,Yue Cheng","doi":"10.1021/acs.jafc.5c14284","DOIUrl":"https://doi.org/10.1021/acs.jafc.5c14284","url":null,"abstract":"Cytochrome P450 monooxygenases are crucial for insect detoxification of xenobiotics. Here, we investigate the function of CYP6AQ1 from Apis cerana cerana (AccCYP6AQ1) in response to pesticide and heavy metal stress. This study reveals that AccCYP6AQ1 is significantly induced by pyrethroid insecticides. In vitro assays demonstrate that the encoded protein directly metabolizes cypermethrin and deltamethrin. Furthermore, through RNAi-mediated silencing, we find that AccCYP6AQ1 also mitigates cadmium- and mercury-induced toxicity. These results indicate that AccCYP6AQ1 participates in a multifunctional detoxification pathway, providing protection against both pesticides and heavy metals. Our results suggest that AccCYP6AQ1 is part of a broader detoxification network, likely representing an ecological adaptation of honey bees to complex chemical mixtures in agricultural environments.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"219 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-26DOI: 10.1021/acs.jafc.5c16528
Lu Yang,Wenzhe Ma
CRISPR/Cas12a technology, characterized by its distinctive trans-cleavage activity, has evolved beyond its gene-editing function to emerge as a powerful tool for molecular detection. This review systematically delineates its structural foundation and molecular mechanism, with a focus on how the technology converts specific nucleic acid recognition into cascade signal amplification. Its applications span pathogen diagnosis, species identification, food safety, and authentication of traditional Chinese medicines. Through integration with isothermal amplification and multimodal detection platforms, Cas12a has driven molecular diagnostics toward portability, visualization, and quantification. The review further discusses challenges related to sensitivity, quantitative accuracy, crRNA design, and standardization, while outlining future directions through convergence with cutting-edge technologies such as microfluidics and artificial intelligence, offering a forward-looking perspective for the development of next-generation precision biosensing platforms.
{"title":"CRISPR/Cas12a: A Comprehensive Review from Structural Foundations to Applications in Nucleic Acid Precision Detection.","authors":"Lu Yang,Wenzhe Ma","doi":"10.1021/acs.jafc.5c16528","DOIUrl":"https://doi.org/10.1021/acs.jafc.5c16528","url":null,"abstract":"CRISPR/Cas12a technology, characterized by its distinctive trans-cleavage activity, has evolved beyond its gene-editing function to emerge as a powerful tool for molecular detection. This review systematically delineates its structural foundation and molecular mechanism, with a focus on how the technology converts specific nucleic acid recognition into cascade signal amplification. Its applications span pathogen diagnosis, species identification, food safety, and authentication of traditional Chinese medicines. Through integration with isothermal amplification and multimodal detection platforms, Cas12a has driven molecular diagnostics toward portability, visualization, and quantification. The review further discusses challenges related to sensitivity, quantitative accuracy, crRNA design, and standardization, while outlining future directions through convergence with cutting-edge technologies such as microfluidics and artificial intelligence, offering a forward-looking perspective for the development of next-generation precision biosensing platforms.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"20 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-26DOI: 10.1021/acs.jafc.5c04528
I-Shuo Huang, Mary Dawn Celiz, John C. Bowers, Jonathan R. Deeds
Several reports have shown that the freshwater cyanobacterial toxins microcystins (MCs) can be transported along the freshwater to marine continuum and can be found in edible marine and estuarine shellfish. However, data for shellfish from commercial harvesting areas is limited. To further assess the concentrations found in these vectors and the risks that they pose to consumers, a validated analytical method is required. Herein, a liquid chromatography-tandem mass spectrometry-based method for the detection of eight MCs (MC-LA, -LF, -LR, -LW, -LY, -RR, -YR, and nodularin-R) was single laboratory validated in Eastern oysters (Crassostrea virginica), blue mussels (Mytilus edulis), hard clams (Mercenaria mercenaria), and softshell clams (Mya arenaria). Median recoveries for all four matrices ranged from 85.3 to 101.0% with RSDs between 3.5 and 14.3%. Overall, the method was found to be accurate, precise, and specific over an extended range of 10–500 μg/kg and determined to be fit for purpose for the screening of MCs in the shellfish matrices tested.
{"title":"Single Laboratory Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantitation of Microcystins in Marine and Estuarine Shellfish","authors":"I-Shuo Huang, Mary Dawn Celiz, John C. Bowers, Jonathan R. Deeds","doi":"10.1021/acs.jafc.5c04528","DOIUrl":"https://doi.org/10.1021/acs.jafc.5c04528","url":null,"abstract":"Several reports have shown that the freshwater cyanobacterial toxins microcystins (MCs) can be transported along the freshwater to marine continuum and can be found in edible marine and estuarine shellfish. However, data for shellfish from commercial harvesting areas is limited. To further assess the concentrations found in these vectors and the risks that they pose to consumers, a validated analytical method is required. Herein, a liquid chromatography-tandem mass spectrometry-based method for the detection of eight MCs (MC-LA, -LF, -LR, -LW, -LY, -RR, -YR, and nodularin-R) was single laboratory validated in Eastern oysters (<i>Crassostrea virginica</i>), blue mussels (<i>Mytilus edulis</i>), hard clams (<i>Mercenaria mercenaria</i>), and softshell clams (<i>Mya arenaria</i>). Median recoveries for all four matrices ranged from 85.3 to 101.0% with RSDs between 3.5 and 14.3%. Overall, the method was found to be accurate, precise, and specific over an extended range of 10–500 μg/kg and determined to be fit for purpose for the screening of MCs in the shellfish matrices tested.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"20 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bisphenol A (BPA), an endocrine-disrupting chemical with estrogenic activity, has been implicated in cancer development, although its role remains controversial. This study investigated the effects of BPA on ovarian cancer and its underlying mechanisms. BPA treatment dose-dependently (0–10 μM) increased cell viability and invasion. Kyoto Encyclopedia of Genes and Genomes analysis revealed the enrichment of the central carbon metabolism pathway following BPA exposure. Consistent with this, BPA upregulated glycolytic enzymes HK2 and LDHA. In addition, BPA activated ERα, which enhanced HK2 transcription and promoted glycolysis. The resulting lactate accumulation increased histone H3 lysine 18 lactylation (H3K18la), enriched at the IGF2BP3 promoter, to upregulate its expression. IGF2BP3 then stabilized HK2 mRNA via m6A recognition, amplifying the glycolysis. Our findings suggest that BPA promotes ovarian cancer progression through the HK2/H3K18la/IGF2BP3 sequential regulatory axis, providing insights for epigenetic-targeted therapies.
{"title":"Bisphenol A Promotes Ovarian Cancer Proliferation and Migration through the HK2/H3K18la/IGF2BP3 Sequential Regulatory Axis","authors":"Xin Xie, Yadi Zhang, Yuanyuan Li, Qi Yan, Jianling Dong, Huimin Zhang, Xiaomeng Guo, Na Guo, Haiyan Xu, Xiaolong Fan, Yun Sun, Biao Hou, Feilong Wang, Fengrui Wu","doi":"10.1021/acs.jafc.5c16242","DOIUrl":"https://doi.org/10.1021/acs.jafc.5c16242","url":null,"abstract":"Bisphenol A (BPA), an endocrine-disrupting chemical with estrogenic activity, has been implicated in cancer development, although its role remains controversial. This study investigated the effects of BPA on ovarian cancer and its underlying mechanisms. BPA treatment dose-dependently (0–10 μM) increased cell viability and invasion. Kyoto Encyclopedia of Genes and Genomes analysis revealed the enrichment of the central carbon metabolism pathway following BPA exposure. Consistent with this, BPA upregulated glycolytic enzymes HK2 and LDHA. In addition, BPA activated ERα, which enhanced HK2 transcription and promoted glycolysis. The resulting lactate accumulation increased histone H3 lysine 18 lactylation (H3K18la), enriched at the IGF2BP3 promoter, to upregulate its expression. IGF2BP3 then stabilized HK2 mRNA via m6A recognition, amplifying the glycolysis. Our findings suggest that BPA promotes ovarian cancer progression through the HK2/H3K18la/IGF2BP3 sequential regulatory axis, providing insights for epigenetic-targeted therapies.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-26DOI: 10.1021/acs.jafc.6c00387
Agápto João Paulo, Júnior Waldir Cintra de Jesus, Afférri Flávio Sérgio, Carmassi Alberto Luciano, Lemos Andressa Cunha, Badiale-Furlong Eliana, Scaglioni Priscila Tessmer
Profiles of deoxynivalenol (DON), 3-acetyl-DON (3-ADON), 15-acetyl-DON (15-ADON), DON-3-glucoside (DON-3G), and nivalenol (NIV) were evaluated in wheat grown in an experimental field under different agronomic conditions regarding their roles in co-contamination with group B trichothecenes (TCTBs). For three years in southwestern Brazil, a susceptible and moderately resistant cultivar was cultivated in irrigated and rainfed systems. A randomized complete block design was carried out to evaluate the effects of the treatments: T1 (fungicide + potassium silicate (KS)), T2 (fungicide), T3 (KS), and T4 (control) on the TCTBs profile that was determined by the validated QuECHERS-HPLC-PAD method. Co-contamination occurred in 79.2% of the samples and the highest level for 15-ADON (1640 μg/kg). In 20 samples, the sum of TCTBs was above the maximum tolerable limit (MTL) for DON (1000 μg/kg). Samples from T1 and T3 had lower contamination levels. It is advisable to consider KS fertilization and include DON forms in MTL to reduce contamination risk.
{"title":"Impact of Wheat Crop Management on Co-occurrence of Group B Trichothecenes: Crop Practices Influencing DON and Derivatives in Wheat","authors":"Agápto João Paulo, Júnior Waldir Cintra de Jesus, Afférri Flávio Sérgio, Carmassi Alberto Luciano, Lemos Andressa Cunha, Badiale-Furlong Eliana, Scaglioni Priscila Tessmer","doi":"10.1021/acs.jafc.6c00387","DOIUrl":"https://doi.org/10.1021/acs.jafc.6c00387","url":null,"abstract":"Profiles of deoxynivalenol (DON), 3-acetyl-DON (3-ADON), 15-acetyl-DON (15-ADON), DON-3-glucoside (DON-3G), and nivalenol (NIV) were evaluated in wheat grown in an experimental field under different agronomic conditions regarding their roles in co-contamination with group B trichothecenes (TCTBs). For three years in southwestern Brazil, a susceptible and moderately resistant cultivar was cultivated in irrigated and rainfed systems. A randomized complete block design was carried out to evaluate the effects of the treatments: T1 (fungicide + potassium silicate (KS)), T2 (fungicide), T3 (KS), and T4 (control) on the TCTBs profile that was determined by the validated QuECHERS-HPLC-PAD method. Co-contamination occurred in 79.2% of the samples and the highest level for 15-ADON (1640 μg/kg). In 20 samples, the sum of TCTBs was above the maximum tolerable limit (MTL) for DON (1000 μg/kg). Samples from T1 and T3 had lower contamination levels. It is advisable to consider KS fertilization and include DON forms in MTL to reduce contamination risk.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"27 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phosphatidylserine (PS), a major brain phospholipid, supports the central nervous system's health and may alleviate cognitive decline, including in Alzheimer's disease. A key challenge in green enzymatic PS synthesis is the suppression of hydrolysis while enhancing PLD-catalyzed transphosphatidylation. Here, we developed a mechanism-guided engineering strategy for Streptomyces antibioticus phospholipase D (SaPLD). The substitution of W187I increased the PS yield to 58.3%, while V380W improved thermostability. Combining beneficial mutations generated SaPLD-R7 (W187I/V380W/G381A), which overcame the activity-stability trade-off and achieved up to 95.8% PS yield using the enzyme produced by 5 L scale fermentation. Molecular dynamics simulations showed that SaPLD-R7 enhanced substrate binding and catalysis by shortening the key active site distances and reducing local flexibility. Solvent contact and energy analyses further indicated improved stability. This work establishes a structure-mechanism-function framework for enhancing PLD transphosphatidylation and provides a robust enzymatic route for high-efficiency PS production as a valuable functional food ingredient.
{"title":"Rational Engineering of Phospholipase D Unlocks Robust Catalysis for Phosphatidylserine Formation.","authors":"Xurui Zhao,Xiufeng Wang,Yijie Sheng,Shuizhi Lin,Shuping Xu,Zhixiang Hu,Xueping Ling,Cuixue Chen,Mingfeng Cao,Haiyang Cui,Yinghua Lu","doi":"10.1021/acs.jafc.5c17951","DOIUrl":"https://doi.org/10.1021/acs.jafc.5c17951","url":null,"abstract":"Phosphatidylserine (PS), a major brain phospholipid, supports the central nervous system's health and may alleviate cognitive decline, including in Alzheimer's disease. A key challenge in green enzymatic PS synthesis is the suppression of hydrolysis while enhancing PLD-catalyzed transphosphatidylation. Here, we developed a mechanism-guided engineering strategy for Streptomyces antibioticus phospholipase D (SaPLD). The substitution of W187I increased the PS yield to 58.3%, while V380W improved thermostability. Combining beneficial mutations generated SaPLD-R7 (W187I/V380W/G381A), which overcame the activity-stability trade-off and achieved up to 95.8% PS yield using the enzyme produced by 5 L scale fermentation. Molecular dynamics simulations showed that SaPLD-R7 enhanced substrate binding and catalysis by shortening the key active site distances and reducing local flexibility. Solvent contact and energy analyses further indicated improved stability. This work establishes a structure-mechanism-function framework for enhancing PLD transphosphatidylation and provides a robust enzymatic route for high-efficiency PS production as a valuable functional food ingredient.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-25DOI: 10.1021/acs.jafc.5c14374
Karishma Tiwari,Yogesh K. Ahlawat,Koustav Dey
Metal–organic frameworks (MOFs), with tunable structures, high porosity, and catalytic activity, are promising platforms for next-generation biosensors. MOF-based nanozymes (MOFzymes) and enzyme–MOF composites combine biological specificity with synthetic robustness, overcoming limitations of natural enzymes in complex environments. This review highlights recent advances in MOF-enabled biosensors for agricultural and healthcare applications, focusing on enzyme immobilization, nanozyme activity, and signal amplification strategies. MOFzymes enable low-cost, portable, and ultrasensitive detection of biomarkers, pathogens, pesticides, and environmental contaminants, although challenges remain in reproducibility, stability, selectivity in complex matrices, and scalable integration.
{"title":"Metal Organic Framework-Based Biosensors for Healthcare and Agricultural Applications","authors":"Karishma Tiwari,Yogesh K. Ahlawat,Koustav Dey","doi":"10.1021/acs.jafc.5c14374","DOIUrl":"https://doi.org/10.1021/acs.jafc.5c14374","url":null,"abstract":"Metal–organic frameworks (MOFs), with tunable structures, high porosity, and catalytic activity, are promising platforms for next-generation biosensors. MOF-based nanozymes (MOFzymes) and enzyme–MOF composites combine biological specificity with synthetic robustness, overcoming limitations of natural enzymes in complex environments. This review highlights recent advances in MOF-enabled biosensors for agricultural and healthcare applications, focusing on enzyme immobilization, nanozyme activity, and signal amplification strategies. MOFzymes enable low-cost, portable, and ultrasensitive detection of biomarkers, pathogens, pesticides, and environmental contaminants, although challenges remain in reproducibility, stability, selectivity in complex matrices, and scalable integration.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"105 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-25DOI: 10.1021/acs.jafc.5c17265
Manman Shi,Xiaoming Yang,Guibin Wang,Fuliang Cao,Yingying Sun,Erzheng Su
Flavonoids are widely distributed in plants, including Ginkgo biloba, a traditional medicinal and edible species. Methylated flavonoids often exhibit enhanced biological activities compared with their unmethylated forms, and flavonoid O-methyltransferases (FOMTs) responsible for this modification have been identified in several plants but remain poorly characterized in ginkgo. In this study, transcriptomic analysis of ginkgo leaves at different developmental stages identified two S-adenosylmethionine-dependent FOMTs, GbFOMT3 and GbFOMT12. Enzymatic assays with seven flavonoid substrates showed that both enzymes methylate quercetin, eriodictyol, and luteolin to produce isorhamnetin, hesperetin, and chrysoeriol, respectively, through methylation at the 3′–OH and 4′–OH positions of the B ring. These findings expand the repertoire of ginkgo flavonoid O-methyltransferases and provide insights into flavonoid methylation in ginkgo.
{"title":"Systematic Analysis Reveals Two Novel O-Methyltransferase Genes Involved in Flavonoid Biosynthesis in Ginkgo Leaves","authors":"Manman Shi,Xiaoming Yang,Guibin Wang,Fuliang Cao,Yingying Sun,Erzheng Su","doi":"10.1021/acs.jafc.5c17265","DOIUrl":"https://doi.org/10.1021/acs.jafc.5c17265","url":null,"abstract":"Flavonoids are widely distributed in plants, including Ginkgo biloba, a traditional medicinal and edible species. Methylated flavonoids often exhibit enhanced biological activities compared with their unmethylated forms, and flavonoid O-methyltransferases (FOMTs) responsible for this modification have been identified in several plants but remain poorly characterized in ginkgo. In this study, transcriptomic analysis of ginkgo leaves at different developmental stages identified two S-adenosylmethionine-dependent FOMTs, GbFOMT3 and GbFOMT12. Enzymatic assays with seven flavonoid substrates showed that both enzymes methylate quercetin, eriodictyol, and luteolin to produce isorhamnetin, hesperetin, and chrysoeriol, respectively, through methylation at the 3′–OH and 4′–OH positions of the B ring. These findings expand the repertoire of ginkgo flavonoid O-methyltransferases and provide insights into flavonoid methylation in ginkgo.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"16 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-25DOI: 10.1021/acs.jafc.5c14456
Wang Geng,Yan Li,Wei Zhang,Jinsong Yang,Kai Yan,Xiuhai Gan
Protoporphyrinogen IX oxidase (PPO) is a key target for herbicide development. To develop novel PPO herbicides, a series of N-phenylphthalimide derivatives bearing benzoxazinone moieties were synthesized. Bioassays showed that compounds B2, A5, A30, and A11 exhibited excellent inhibitory activity against Nicotiana tabacum PPO (NtPPO) with Ki values of 9.50, 17.8, 11.2, and 11.7 nM, respectively─outperforming flumioxazin (Ki = 52.0 nM). At 9.375 g a.i./ha, B2 and A30 achieved over 80% control efficacy against three broadleaf weeds; they also displayed broad-spectrum herbicidal activity at 75 g a.i./ha, with a low injury index toward wheat, rice, and maize even at 150 g a.i./ha. Molecular docking indicated that B2 and A30 formed stable H-bonds with Arg98 (2.7 Å), π–π stacking with Phe392, and sandwich π–alkyl interactions with Leu356/Leu372. Molecular dynamics simulations and Gibbs free energy analysis confirmed their stable binding to NtPPO (A30, ΔGbind = −44.50 kcal/mol; B2, ΔGbind = −33.03 kcal/mol) with suitable conformational dynamics. Overall, B2 and A30 are promising PPO inhibitors for agricultural weed control.
原卟啉原IX氧化酶（PPO）是除草剂开发的重要靶点。为开发新型PPO除草剂，合成了一系列含苯并恶嗪酮基团的n -苯酞酰亚胺衍生物。生物实验表明，化合物B2、A5、A30和A11对烟草PPO （NtPPO）具有较好的抑制活性，其Ki值分别为9.50、17.8、11.2和11.7 nM，优于氟咪唑嗪（Ki = 52.0 nM）。在9.375 g a.i./ha时，B2和A30对3种阔叶杂草的防效达到80%以上；在75 g a.i./ha时表现出广谱除草活性，在150 g a.i./ha时对小麦、水稻和玉米的伤害指数较低。分子对接表明，B2和A30与Arg98 （2.7 Å）形成稳定的氢键，与Phe392形成π -π堆叠，与Leu356/Leu372形成夹层π -烷基相互作用。分子动力学模拟和Gibbs自由能分析证实了它们与NtPPO （A30， ΔGbind =−44.50 kcal/mol; B2， ΔGbind =−33.03 kcal/mol）的稳定结合，具有合适的构象动力学。综上所述，B2和A30是很有希望用于农业杂草防治的PPO抑制剂。
{"title":"Design, Synthesis and Biological Evaluation of N-Phenylphthalimide Protoporphyrinogen IX Oxidase Inhibitor Herbicides","authors":"Wang Geng,Yan Li,Wei Zhang,Jinsong Yang,Kai Yan,Xiuhai Gan","doi":"10.1021/acs.jafc.5c14456","DOIUrl":"https://doi.org/10.1021/acs.jafc.5c14456","url":null,"abstract":"Protoporphyrinogen IX oxidase (PPO) is a key target for herbicide development. To develop novel PPO herbicides, a series of N-phenylphthalimide derivatives bearing benzoxazinone moieties were synthesized. Bioassays showed that compounds B2, A5, A30, and A11 exhibited excellent inhibitory activity against Nicotiana tabacum PPO (NtPPO) with Ki values of 9.50, 17.8, 11.2, and 11.7 nM, respectively─outperforming flumioxazin (Ki = 52.0 nM). At 9.375 g a.i./ha, B2 and A30 achieved over 80% control efficacy against three broadleaf weeds; they also displayed broad-spectrum herbicidal activity at 75 g a.i./ha, with a low injury index toward wheat, rice, and maize even at 150 g a.i./ha. Molecular docking indicated that B2 and A30 formed stable H-bonds with Arg98 (2.7 Å), π–π stacking with Phe392, and sandwich π–alkyl interactions with Leu356/Leu372. Molecular dynamics simulations and Gibbs free energy analysis confirmed their stable binding to NtPPO (A30, ΔGbind = −44.50 kcal/mol; B2, ΔGbind = −33.03 kcal/mol) with suitable conformational dynamics. Overall, B2 and A30 are promising PPO inhibitors for agricultural weed control.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"224 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Plant virus infection can trigger autophagy and remodel autophagosomes to benefit viral propagation in vector insects. Rice gall dwarf virus (RGDV) triggers the incomplete autophagy to promote viral spread in Recilia dorsalis, yet the autophagy initiation remains unclear. Here, we discovered that the dual-role ATG1–ATG13 complex acts as a crucial switch in initiating or inhibiting autophagy in RGDV-infected R. dorsalis. RGDV infection or microinjection of RGDV Pns11 reduces the accumulation of phosphorylated ATG1–ATG13 complex and stimulates autophagy in insects. Additionally, Pns11 interacts with ATG13 and recruits the phosphatase PP4C to effectively dephosphorylate ATG13 for stimulating autophagy in insects. However, p38 MAPK is dynamically upregulated to phosphorylate ATG1–ATG13 complex in RGDV-infected insects. Inhibiting the expression or kinase activity of p38 MAPK both promotes autophagosomes formation and viral propagation, but reduces the survival rate of insects. Taken together, these findings demonstrate how rice reoviruses and vector insects regulate the phosphorylation of the dual-role ATG1–ATG13 complex to maintain moderate autophagy for viral persistent propagation in insect vectors.
植物病毒感染可引发自噬并重塑自噬体，从而有利于病毒在媒介昆虫中的传播。水稻瘿矮病毒（Rice gall dwarf virus， RGDV）通过触发不完全自噬来促进病毒在背霉中的传播，但自噬的起始机制尚不清楚。在这里，我们发现双重作用的ATG1-ATG13复合物在启动或抑制rgdv感染的背孢子虫自噬中起着关键的开关作用。RGDV感染或显微注射RGDV Pns11可减少磷酸化ATG1-ATG13复合物的积累，刺激昆虫自噬。此外，Pns11与ATG13相互作用，募集磷酸酶PP4C，有效地使ATG13去磷酸化，刺激昆虫自噬。然而，在rgdv感染的昆虫中，p38 MAPK动态上调以磷酸化ATG1-ATG13复合物。抑制p38 MAPK的表达或激酶活性既能促进自噬体的形成和病毒的繁殖，又能降低昆虫的存活率。综上所述，这些发现证明了水稻呼肠孤病毒和媒介昆虫如何调节双重作用ATG1-ATG13复合物的磷酸化，以维持病毒在昆虫媒介中持续传播的适度自噬。
{"title":"Plant Virus and Vector Insect Regulate the Dual Phosphorylation of ATG1–ATG13 To Maintain a Moderate Autophagy for Viral Persistent Propagation","authors":"Linyu Liu,Wang Guan,Taihui Li,Guangjun Li,Xinyi Liang,Taiyun Wei,Dongsheng Jia","doi":"10.1021/acs.jafc.6c00361","DOIUrl":"https://doi.org/10.1021/acs.jafc.6c00361","url":null,"abstract":"Plant virus infection can trigger autophagy and remodel autophagosomes to benefit viral propagation in vector insects. Rice gall dwarf virus (RGDV) triggers the incomplete autophagy to promote viral spread in Recilia dorsalis, yet the autophagy initiation remains unclear. Here, we discovered that the dual-role ATG1–ATG13 complex acts as a crucial switch in initiating or inhibiting autophagy in RGDV-infected R. dorsalis. RGDV infection or microinjection of RGDV Pns11 reduces the accumulation of phosphorylated ATG1–ATG13 complex and stimulates autophagy in insects. Additionally, Pns11 interacts with ATG13 and recruits the phosphatase PP4C to effectively dephosphorylate ATG13 for stimulating autophagy in insects. However, p38 MAPK is dynamically upregulated to phosphorylate ATG1–ATG13 complex in RGDV-infected insects. Inhibiting the expression or kinase activity of p38 MAPK both promotes autophagosomes formation and viral propagation, but reduces the survival rate of insects. Taken together, these findings demonstrate how rice reoviruses and vector insects regulate the phosphorylation of the dual-role ATG1–ATG13 complex to maintain moderate autophagy for viral persistent propagation in insect vectors.","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":"19 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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