Pub Date : 2024-06-21DOI: 10.1021/acs.jafc.4c01827
Sanjai Karanth, Julia Benthin, Marina Wiesenfarth, Veronika Somoza and Melanie Koehler*,
Chemosensory membrane proteins such as G-protein-coupled receptors (GPCRs) drive flavor perception of food formulations. To achieve this, a detailed understanding of the structure and function of these membrane proteins is needed, which is often limited by the extraction and purification methods involved. The proposed nanodisc methodology helps overcome some of these existing challenges such as protein stability and solubilization along with their reconstitution from a native cell-membrane environment. Being well-established in structural biology procedures, nanodiscs offer this elegant solution by using, e.g., a membrane scaffold protein (MSP) or styrene–maleic acid (SMA) polymer, which interacts directly with the cell membrane during protein reconstitution. Such derived proteins retain their biophysical properties without compromising the membrane architecture. Here, we seek to show that these lipidic systems can be explored for insights with a focus on chemosensory membrane protein morphology and structure, conformational dynamics of protein–ligand interactions, and binding kinetics to answer pending questions in flavor research. Additionally, the compatibility of nanodiscs across varied (labeled or label-free) techniques offers significant leverage, which has been highlighted here.
G 蛋白偶联受体(GPCR)等化感膜蛋白驱动着食品配方的风味感知。为此,需要详细了解这些膜蛋白的结构和功能,而这往往受到提取和纯化方法的限制。拟议的纳米盘方法有助于克服现有的一些挑战,如蛋白质的稳定性和溶解性,以及从原生细胞膜环境中进行重组。纳米盘在结构生物学程序中已得到广泛应用,它通过使用膜支架蛋白(MSP)或苯乙烯-马来酸(SMA)聚合物等,在蛋白质重组过程中直接与细胞膜相互作用,从而提供了优雅的解决方案。这种衍生蛋白质在保持其生物物理特性的同时不会破坏膜结构。在此,我们试图表明,这些脂质系统可用于探索化学感受膜蛋白的形态和结构、蛋白质配体相互作用的构象动力学以及结合动力学,以回答风味研究中有待解决的问题。此外,纳米光盘在各种(标记或无标记)技术中的兼容性也提供了重要的优势,这一点已在此作了强调。
{"title":"Nanodisc Technology: Direction toward Physicochemical Characterization of Chemosensory Membrane Proteins in Food Flavor Research","authors":"Sanjai Karanth, Julia Benthin, Marina Wiesenfarth, Veronika Somoza and Melanie Koehler*, ","doi":"10.1021/acs.jafc.4c01827","DOIUrl":"10.1021/acs.jafc.4c01827","url":null,"abstract":"<p >Chemosensory membrane proteins such as G-protein-coupled receptors (GPCRs) drive flavor perception of food formulations. To achieve this, a detailed understanding of the structure and function of these membrane proteins is needed, which is often limited by the extraction and purification methods involved. The proposed nanodisc methodology helps overcome some of these existing challenges such as protein stability and solubilization along with their reconstitution from a native cell-membrane environment. Being well-established in structural biology procedures, nanodiscs offer this elegant solution by using, e.g., a membrane scaffold protein (MSP) or styrene–maleic acid (SMA) polymer, which interacts directly with the cell membrane during protein reconstitution. Such derived proteins retain their biophysical properties without compromising the membrane architecture. Here, we seek to show that these lipidic systems can be explored for insights with a focus on chemosensory membrane protein morphology and structure, conformational dynamics of protein–ligand interactions, and binding kinetics to answer pending questions in flavor research. Additionally, the compatibility of nanodiscs across varied (labeled or label-free) techniques offers significant leverage, which has been highlighted here.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jafc.4c01827","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-21DOI: 10.1021/acs.jafc.3c08693
Yu Chen, Weilong Xu, Mian Du, Longzhu Bao, Jun Li, Qianqian Zhai*, Dingce Yan and Huailong Teng*,
The development of new fungicide molecules is a crucial task for agricultural chemists to enhance the effectiveness of fungicides in agricultural production. In this study, a series of novel fluoroalkenyl modified succinate dehydrogenase inhibitors were synthesized and evaluated for their antifungal activities against eight fungi. The results from the in vitro antifungal assay demonstrated that compound 34 exhibited superior activity against Rhizoctonia solani with an EC50 value of 0.04 μM, outperforming commercial fluxapyroxad (EC50 = 0.18 μM) and boscalid (EC50 = 3.07 μM). Furthermore, compound 34 showed similar effects to fluxapyroxad on other pathogenic fungi such as Sclerotinia sclerotiorum (EC50 = 1.13 μM), Monilinia fructicola (EC50 = 1.61 μM), Botrytis cinerea (EC50 = 1.21 μM), and also demonstrated protective and curative efficacies in vivo on rapeseed leaves and tomato fruits. Enzyme activity experiments and protein–ligand interaction analysis by surface plasmon resonance revealed that compound 34 had a stronger inhibitory effect on succinate dehydrogenase compared to fluxapyroxad. Additionally, molecular docking and DFT calculation confirmed that the fluoroalkenyl unit in compound 34 could enhance its binding capacity with the target protein through p−π conjugation and hydrogen bond interactions.
{"title":"Design, Synthesis, and Antifungal Activities of Novel Potent Fluoroalkenyl Succinate Dehydrogenase Inhibitors","authors":"Yu Chen, Weilong Xu, Mian Du, Longzhu Bao, Jun Li, Qianqian Zhai*, Dingce Yan and Huailong Teng*, ","doi":"10.1021/acs.jafc.3c08693","DOIUrl":"10.1021/acs.jafc.3c08693","url":null,"abstract":"<p >The development of new fungicide molecules is a crucial task for agricultural chemists to enhance the effectiveness of fungicides in agricultural production. In this study, a series of novel fluoroalkenyl modified succinate dehydrogenase inhibitors were synthesized and evaluated for their antifungal activities against eight fungi. The results from the <i>in vitro</i> antifungal assay demonstrated that compound <b>34</b> exhibited superior activity against <i>Rhizoctonia solani</i> with an EC<sub>50</sub> value of 0.04 μM, outperforming commercial fluxapyroxad (EC<sub>50</sub> = 0.18 μM) and boscalid (EC<sub>50</sub> = 3.07 μM). Furthermore, compound <b>34</b> showed similar effects to fluxapyroxad on other pathogenic fungi such as <i>Sclerotinia sclerotiorum</i> (EC<sub>50</sub> = 1.13 μM), <i>Monilinia fructicola</i> (EC<sub>50</sub> = 1.61 μM), <i>Botrytis cinerea</i> (EC<sub>50</sub> = 1.21 μM), and also demonstrated protective and curative efficacies <i>in vivo</i> on rapeseed leaves and tomato fruits. Enzyme activity experiments and protein–ligand interaction analysis by surface plasmon resonance revealed that compound <b>34</b> had a stronger inhibitory effect on succinate dehydrogenase compared to fluxapyroxad. Additionally, molecular docking and DFT calculation confirmed that the fluoroalkenyl unit in compound <b>34</b> could enhance its binding capacity with the target protein through p−π conjugation and hydrogen bond interactions.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436438","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 : 2024-06-21DOI: 10.1021/acs.jafc.4c02657
Marie-Christin Norwig, Sabrina Geisslitz and Katharina A. Scherf*,
Wheat species with various ploidy levels may be different regarding their immunoreactive potential in celiac disease (CD), but a comprehensive comparison of peptide sequences with known epitopes is missing. Thus, we used an untargeted liquid chromatography tandem mass spectrometry method to analyze the content of peptides with CD-active epitope in the five wheat species common wheat, spelt, durum wheat, emmer, and einkorn. In total, 494 peptides with CD-active epitope were identified. Considering the average of the eight cultivars of each species, spelt contained the highest number of different peptides with CD-active epitope (193 ± 12, mean ± SD). Einkorn showed the smallest variability of peptides (63 ± 4) but higher amounts of certain peptides compared to the other species. The wheat species differ in the presence and distribution of CD-active epitopes; hence, the entirety of peptides with CD-active epitope is crucial for the assessment of their immunoreactive potential.
不同倍性水平的小麦品种对乳糜泻(CD)的免疫反应潜力可能不同,但目前还缺乏对具有已知表位的肽序列的全面比较。因此,我们采用非靶向液相色谱串联质谱法分析了普通小麦、斯佩尔特小麦、硬质小麦、埃默尔小麦和黑麦这五种小麦中具有乳糜泻活性表位的肽的含量。共鉴定出 494 个具有 CD 活性表位的肽。从每个品种八个栽培品种的平均值来看,斯佩耳特小麦含有CD活性表位的不同肽的数量最多(193±12,平均值±标度)。Einkorn小麦的肽变异性最小(63 ± 4),但与其他品种相比,某些肽的含量较高。小麦物种在 CD 活性表位的存在和分布方面存在差异;因此,具有 CD 活性表位的肽的整体性对于评估其免疫反应潜力至关重要。
{"title":"Comparative Label-Free Proteomics Study on Celiac Disease-Active Epitopes in Common Wheat, Spelt, Durum Wheat, Emmer, and Einkorn","authors":"Marie-Christin Norwig, Sabrina Geisslitz and Katharina A. Scherf*, ","doi":"10.1021/acs.jafc.4c02657","DOIUrl":"10.1021/acs.jafc.4c02657","url":null,"abstract":"<p >Wheat species with various ploidy levels may be different regarding their immunoreactive potential in celiac disease (CD), but a comprehensive comparison of peptide sequences with known epitopes is missing. Thus, we used an untargeted liquid chromatography tandem mass spectrometry method to analyze the content of peptides with CD-active epitope in the five wheat species common wheat, spelt, durum wheat, emmer, and einkorn. In total, 494 peptides with CD-active epitope were identified. Considering the average of the eight cultivars of each species, spelt contained the highest number of different peptides with CD-active epitope (193 ± 12, mean ± SD). Einkorn showed the smallest variability of peptides (63 ± 4) but higher amounts of certain peptides compared to the other species. The wheat species differ in the presence and distribution of CD-active epitopes; hence, the entirety of peptides with CD-active epitope is crucial for the assessment of their immunoreactive potential.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jafc.4c02657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-20DOI: 10.1021/acs.jafc.4c03128
Zhen Li, Lina Sun, Yulu Wang, Bolin Liu and Fengjiao Xin*,
Vanillin is one of the world’s most extensively used flavoring agents with high application value. However, the yield of vanillin biosynthesis remains limited due to the low efficiency of substrate uptake and the inhibitory effect on cell growth caused by vanillin. Here, we screened high-efficiency ferulic acid importer TodX and vanillin exporters PP_0178 and PP_0179 by overexpressing genes encoding candidate transporters in a vanillin-producing engineered Escherichia coli strain VA and further constructed an autoregulatory bidirectional transport system by coexpressing TodX and PP_0178/PP_0179 with a vanillin self-inducible promoter ADH7. Compared with strain VA, strain VA-TodX-PP_0179 can efficiently transport ferulic acid across the cell membrane and convert it to vanillin, which significantly increases the substrate utilization rate efficiency (14.86%) and vanillin titer (51.07%). This study demonstrated that the autoregulatory bidirectional transport system significantly enhances the substrate uptake efficiency while alleviating the vanillin toxicity issue, providing a promising viable route for vanillin biosynthesis.
香兰素是世界上最广泛使用的调味剂之一,具有很高的应用价值。然而,由于底物吸收效率低以及香兰素对细胞生长的抑制作用,香兰素生物合成的产量仍然有限。在此,我们通过在生产香兰素的工程大肠杆菌菌株 VA 中过表达编码候选转运体的基因,筛选出了高效阿魏酸导入体 TodX 和香兰素导出体 PP_0178 和 PP_0179,并通过在香兰素自诱导启动子 ADH7 上共表达 TodX 和 PP_0178/PP_0179 进一步构建了自调节双向转运系统。与 VA 菌株相比,VA-TodX-PP_0179 菌株能高效地将阿魏酸跨细胞膜转运并转化为香兰素,从而显著提高了底物利用率(14.86%)和香兰素滴度(51.07%)。这项研究表明,自律性双向转运系统能显著提高底物吸收效率,同时缓解香兰素毒性问题,为香兰素的生物合成提供了一条可行的途径。
{"title":"Construction of a Novel Vanillin-Induced Autoregulating Bidirectional Transport System in a Vanillin-Producing E. coli Cell Factory","authors":"Zhen Li, Lina Sun, Yulu Wang, Bolin Liu and Fengjiao Xin*, ","doi":"10.1021/acs.jafc.4c03128","DOIUrl":"10.1021/acs.jafc.4c03128","url":null,"abstract":"<p >Vanillin is one of the world’s most extensively used flavoring agents with high application value. However, the yield of vanillin biosynthesis remains limited due to the low efficiency of substrate uptake and the inhibitory effect on cell growth caused by vanillin. Here, we screened high-efficiency ferulic acid importer TodX and vanillin exporters PP_0178 and PP_0179 by overexpressing genes encoding candidate transporters in a vanillin-producing engineered <i>Escherichia coli</i> strain VA and further constructed an autoregulatory bidirectional transport system by coexpressing TodX and PP_0178/PP_0179 with a vanillin self-inducible promoter <i>ADH7</i>. Compared with strain VA, strain VA-TodX-PP_0179 can efficiently transport ferulic acid across the cell membrane and convert it to vanillin, which significantly increases the substrate utilization rate efficiency (14.86%) and vanillin titer (51.07%). This study demonstrated that the autoregulatory bidirectional transport system significantly enhances the substrate uptake efficiency while alleviating the vanillin toxicity issue, providing a promising viable route for vanillin biosynthesis.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425694","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 : 2024-06-20DOI: 10.1021/acs.jafc.4c02611
Mingtao Zhao, Baohui Zhang, Xiaofeng Wu and Yi Xiao*,
Monolignols and their derivatives exhibit various pharmaceutical and physiological characteristics, such as antioxidant and anti-inflammatory properties. However, they remain difficult to synthesize. In this study, we engineered several whole-cell bioconversion systems with carboxylate reductase (CAR)-mediated pathways for efficient synthesis of p-coumaryl, caffeyl, and coniferyl alcohols from l-tyrosine in Escherichia coli BL21 (DE3). By overexpressing the l-tyrosine ammonia lyase from Flavobacterium johnsoniae (FjTAL), carboxylate reductase from Segniliparus rugosus (SruCAR), alcohol dehydrogenase YqhD and hydroxylase HpaBC from E. coli, and caffeate 3-O-methyltransferase (COMT) from Arabidopsis thaliana, three enzyme cascades FjTAL–SruCAR–YqhD, FjTAL–SruCAR–YqhD–HpaBC, and FjTAL–SruCAR–YqhD–HpaBC–COMT were constructed to produce 1028.5 mg/L p-coumaryl alcohol, 1015.3 mg/L caffeyl alcohol, and 411.4 mg/L coniferyl alcohol from 1500, 1500, and 1000 mg/L l-tyrosine, with productivities of 257.1, 203.1, and 82.3 mg/L/h, respectively. This work provides an efficient strategy for the biosynthesis of p-coumaryl, caffeyl, and coniferyl alcohols from l-tyrosine.
{"title":"Whole-Cell Bioconversion Systems for Efficient Synthesis of Monolignols from L-Tyrosine in Escherichia coli","authors":"Mingtao Zhao, Baohui Zhang, Xiaofeng Wu and Yi Xiao*, ","doi":"10.1021/acs.jafc.4c02611","DOIUrl":"10.1021/acs.jafc.4c02611","url":null,"abstract":"<p >Monolignols and their derivatives exhibit various pharmaceutical and physiological characteristics, such as antioxidant and anti-inflammatory properties. However, they remain difficult to synthesize. In this study, we engineered several whole-cell bioconversion systems with carboxylate reductase (CAR)-mediated pathways for efficient synthesis of <i>p</i>-coumaryl, caffeyl, and coniferyl alcohols from <span>l</span>-tyrosine in <i>Escherichia coli</i> BL21 (DE3). By overexpressing the <span>l</span>-tyrosine ammonia lyase from <i>Flavobacterium johnsoniae</i> (FjTAL), carboxylate reductase from <i>Segniliparus rugosus</i> (SruCAR), alcohol dehydrogenase YqhD and hydroxylase HpaBC from <i>E. coli</i>, and caffeate 3-O-methyltransferase (COMT) from <i>Arabidopsis thaliana</i>, three enzyme cascades FjTAL–SruCAR–YqhD, FjTAL–SruCAR–YqhD–HpaBC, and FjTAL–SruCAR–YqhD–HpaBC–COMT were constructed to produce 1028.5 mg/L <i>p</i>-coumaryl alcohol, 1015.3 mg/L caffeyl alcohol, and 411.4 mg/L coniferyl alcohol from 1500, 1500, and 1000 mg/L <span>l</span>-tyrosine, with productivities of 257.1, 203.1, and 82.3 mg/L/h, respectively. This work provides an efficient strategy for the biosynthesis of <i>p</i>-coumaryl, caffeyl, and coniferyl alcohols from <span>l</span>-tyrosine.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425651","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 : 2024-06-20DOI: 10.1021/acs.jafc.4c02876
Yuhan Qiu, Chuanshuang Hu*, Jiewen Li, Qin Lai, Ziling Liu, Xiuyi Lin and Weiwei Zhang*,
Although γ-methacryloxypropyltrimethoxysilane (MPS) was proved to be an effective reagent for improving the dimensional stability of wood, a bottleneck in ASE value (around 50%) existed. The reason was that MPS with low polarity opened few hydrogen bonds in the amorphous region of cellulose, while these hydrogen bonds could be reopened by water. Therefore, citric acid (CA) is chosen to cooperate with MPS to further enhance the dimensional stability of wood. In this paper, MPS and CA were used to modify wood individually (MW and CW) or with different combinations, that is, one-step modification (M/CW) and two-step modification with MPS first (M-CW) or CA first (C-MW). CA and MPS concentrations were optimized at 5 wt%. The ASE value for M/CW was only 25.74% at a weight percent gain (WPG) of 6.43%, which was only 0.6 times to MW or 0.7 times to CW. For M-CW, the ASE value gradually decreased with the soaking cycles, from 65.64% at a WPG of 9.05% to 51.20%. The C-MW had the best dimensional stability, with the ASE value 75.35% at a WPG of 11.50%. Although it decreased during the first soaking cycle, it stabilized at 62.20% at last. SEM and EDS images showed that the polymer mainly distributed in cell walls and few in cell lumen in C-MW. Thus, the enhanced dimensional stability of C-MW could be explained by CA opening the hydrogen bonds in the amorphous region of cellulose first, which provided more binding sites for MPS.
{"title":"Cell Wall Modification Based on Combination Reagents to Improve Dimensional Stability of Wood with High Efficiency","authors":"Yuhan Qiu, Chuanshuang Hu*, Jiewen Li, Qin Lai, Ziling Liu, Xiuyi Lin and Weiwei Zhang*, ","doi":"10.1021/acs.jafc.4c02876","DOIUrl":"10.1021/acs.jafc.4c02876","url":null,"abstract":"<p >Although γ-methacryloxypropyltrimethoxysilane (MPS) was proved to be an effective reagent for improving the dimensional stability of wood, a bottleneck in ASE value (around 50%) existed. The reason was that MPS with low polarity opened few hydrogen bonds in the amorphous region of cellulose, while these hydrogen bonds could be reopened by water. Therefore, citric acid (CA) is chosen to cooperate with MPS to further enhance the dimensional stability of wood. In this paper, MPS and CA were used to modify wood individually (MW and CW) or with different combinations, that is, one-step modification (M/CW) and two-step modification with MPS first (M-CW) or CA first (C-MW). CA and MPS concentrations were optimized at 5 wt%. The ASE value for M/CW was only 25.74% at a weight percent gain (WPG) of 6.43%, which was only 0.6 times to MW or 0.7 times to CW. For M-CW, the ASE value gradually decreased with the soaking cycles, from 65.64% at a WPG of 9.05% to 51.20%. The C-MW had the best dimensional stability, with the ASE value 75.35% at a WPG of 11.50%. Although it decreased during the first soaking cycle, it stabilized at 62.20% at last. SEM and EDS images showed that the polymer mainly distributed in cell walls and few in cell lumen in C-MW. Thus, the enhanced dimensional stability of C-MW could be explained by CA opening the hydrogen bonds in the amorphous region of cellulose first, which provided more binding sites for MPS.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425693","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 : 2024-06-20DOI: 10.1021/acs.jafc.4c02572
Kairui Wang, Ning Liu, Minghao Liu*, Pan Zhao, Naiqin Zhong, Gregory L. Challis and Ying Huang*,
Potato common scab (PCS) is a widespread plant disease that lacks effective control measures. Using a small molecule elicitor, we activate the production of a novel class of polyketide antibiotics, streptolateritic acids A–D, in Streptomyces sp. FXJ1.172. These compounds show a promising control efficacy against PCS and an unusual acyclic pentacarboxylic acid structure. A gene cluster encoding a type I modular polyketide synthase is identified to be responsible for the biosynthesis of these metabolites. A cytochrome P450 (CYP) and an aldehyde dehydrogenase (ADH) encoded by two genes in the cluster are proposed to catalyze iterative oxidation of the starter-unit-derived methyl group and three of six branching methyl groups to carboxylic acids during chain assembly. Our findings highlight how activation of silent biosynthetic gene clusters can be employed to discover completely new natural product classes able to combat PCS and new types of modular polyketide synthase-based biosynthetic machinery.
{"title":"Discovery and Biosynthesis of Streptolateritic Acids A–D: Acyclic Pentacarboxylic Acids from Streptomyces sp. FXJ1.172 with Promising Activity against Potato Common Scab","authors":"Kairui Wang, Ning Liu, Minghao Liu*, Pan Zhao, Naiqin Zhong, Gregory L. Challis and Ying Huang*, ","doi":"10.1021/acs.jafc.4c02572","DOIUrl":"10.1021/acs.jafc.4c02572","url":null,"abstract":"<p >Potato common scab (PCS) is a widespread plant disease that lacks effective control measures. Using a small molecule elicitor, we activate the production of a novel class of polyketide antibiotics, streptolateritic acids A–D, in <i>Streptomyces</i> sp. FXJ1.172. These compounds show a promising control efficacy against PCS and an unusual acyclic pentacarboxylic acid structure. A gene cluster encoding a type I modular polyketide synthase is identified to be responsible for the biosynthesis of these metabolites. A cytochrome P450 (CYP) and an aldehyde dehydrogenase (ADH) encoded by two genes in the cluster are proposed to catalyze iterative oxidation of the starter-unit-derived methyl group and three of six branching methyl groups to carboxylic acids during chain assembly. Our findings highlight how activation of silent biosynthetic gene clusters can be employed to discover completely new natural product classes able to combat PCS and new types of modular polyketide synthase-based biosynthetic machinery.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425696","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 : 2024-06-20DOI: 10.1021/acs.jafc.4c03768
Yen-Chun Koh, Han-Wen Hsu, Pin-Yu Ho, Kai-Yu Hsu, Wei-Sheng Lin, Kalyanam Nagabhushanam, Chi-Tang Ho and Min-Hsiung Pan*,
Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.
在以往的研究中,一些姜黄素热降解剂显示出了适度的健康益处。阿魏酰丙酮(FER)最近被确认为姜黄素的一种热降解剂,以前曾被认为具有抗癌和抗氧化作用,但它的其他功能仍有待探索。此外,早前的报告表明,芳香环上的甲氧基可能会影响姜黄素的功能。为了填补这些空白,我们开展了一项动物实验,研究 FER 及其去甲氧基对应物(DFER)对高脂饮食小鼠的抗肥胖作用。结果表明,这两种样品都能明显防止体重增加以及肝脏和各种脂肪组织的增大。此外,这些营养补充剂还通过脂肪连通素/AMPK/SIRT1途径对肝脏中的脂质产生调节作用,通过激活AMPK/PGC-1α促进产热,并对肠道微生物产生的短链脂肪酸(SCFA)水平产生积极影响。值得注意的是,DFER 在对抗肥胖方面表现出更优越的整体功效,而 FER 则在调节炎症反应方面表现出显著效果。在动物实验中,SCFA 可能是 FER 和 DFER 产生不同效果的原因。预计未来的研究将深入探讨姜黄素降解剂的功效,包括毒性和药代动力学评估。
{"title":"Structural Variances in Curcumin Degradants: Impact on Obesity in Mice","authors":"Yen-Chun Koh, Han-Wen Hsu, Pin-Yu Ho, Kai-Yu Hsu, Wei-Sheng Lin, Kalyanam Nagabhushanam, Chi-Tang Ho and Min-Hsiung Pan*, ","doi":"10.1021/acs.jafc.4c03768","DOIUrl":"10.1021/acs.jafc.4c03768","url":null,"abstract":"<p >Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jafc.4c03768","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1021/acs.jafc.4c04242
Nadia Pérez-Fuentes, Rebeca Alvariño*, Amparo Alfonso*, Jesús González-Jartín, Mercedes R. Vieytes and Luis M. Botana,
Enniatins (ENNs) A1 and B1, previously considered ionophores, are emerging mycotoxins with effects on Ca2+ homeostasis. However, their exact mechanism of action remains unclear. This study investigated how these toxins affect Ca2+ flux in SH-SY5Y cells. ENN A1 induced Ca2+ influx through store-operated channels (SOC). The mitochondrial uncoupler FCCP reduced this influx, suggesting that the mitochondrial status influences the toxin effect. Conversely, ENN B1 did not affect SOC but acted on another Ca2+ channel, as shown when nickel, which directly blocks the Ca2+ channel pore, is added. Mitochondrial function also influenced the effects of ENN B1, as treatment with FCCP reduced toxin-induced Ca2+ depletion and uptake. In addition, both ENNs altered mitochondrial function by producing the opening of the mitochondrial permeability transition pore. This study describes for the first time that ENN A1 and B1 are not Ca2+ ionophores and suggests a different mechanism of action for each toxin.
{"title":"Enniatins A1 and B1 Modulate Calcium Flux through Alternative Pathways beyond Mitochondria","authors":"Nadia Pérez-Fuentes, Rebeca Alvariño*, Amparo Alfonso*, Jesús González-Jartín, Mercedes R. Vieytes and Luis M. Botana, ","doi":"10.1021/acs.jafc.4c04242","DOIUrl":"10.1021/acs.jafc.4c04242","url":null,"abstract":"<p >Enniatins (ENNs) A1 and B1, previously considered ionophores, are emerging mycotoxins with effects on Ca<sup>2+</sup> homeostasis. However, their exact mechanism of action remains unclear. This study investigated how these toxins affect Ca<sup>2+</sup> flux in SH-SY5Y cells. ENN A1 induced Ca<sup>2+</sup> influx through store-operated channels (SOC). The mitochondrial uncoupler FCCP reduced this influx, suggesting that the mitochondrial status influences the toxin effect. Conversely, ENN B1 did not affect SOC but acted on another Ca<sup>2+</sup> channel, as shown when nickel, which directly blocks the Ca<sup>2+</sup> channel pore, is added. Mitochondrial function also influenced the effects of ENN B1, as treatment with FCCP reduced toxin-induced Ca<sup>2+</sup> depletion and uptake. In addition, both ENNs altered mitochondrial function by producing the opening of the mitochondrial permeability transition pore. This study describes for the first time that ENN A1 and B1 are not Ca<sup>2+</sup> ionophores and suggests a different mechanism of action for each toxin.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jafc.4c04242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1021/acs.jafc.4c01616
Denis Barron*, Yann Ratinaud, Simona Rambousek, Benjamin Brinon, Martine Naranjo Pinta, Matthew J Sanders, Kei Sakamoto and Olivier Ciclet,
These days, easy access to commercially available (poly)phenolic compounds has expanded the scope of potential research beyond the field of chemistry, particularly in the area of their bioactivity. However, the quality of these compounds is often overlooked or not even considered. This issue is illustrated in this study through the example of (dihydro)phenanthrenes, a group of natural products present in yams, as AMP-activated protein kinase (AMPK) activators. A study conducted in our group on a series of compounds, fully characterized using a combination of chemical synthesis, NMR and MS techniques, provided evidence that the conclusions of a previous study were erroneous, likely due to the use of a misidentified commercial compound by its supplier. Furthermore, we demonstrated that additional representatives of the (dihydro)phenanthrene phytochemical classes were able to directly activate AMPK, avoiding the risk of misinterpretation of results based on analysis of a single compound alone.
{"title":"Unambiguous Characterization of Commercial Natural (Dihydro)phenanthrene Compounds Is Vital in the Discovery of AMPK Activators","authors":"Denis Barron*, Yann Ratinaud, Simona Rambousek, Benjamin Brinon, Martine Naranjo Pinta, Matthew J Sanders, Kei Sakamoto and Olivier Ciclet, ","doi":"10.1021/acs.jafc.4c01616","DOIUrl":"10.1021/acs.jafc.4c01616","url":null,"abstract":"<p >These days, easy access to commercially available (poly)phenolic compounds has expanded the scope of potential research beyond the field of chemistry, particularly in the area of their bioactivity. However, the quality of these compounds is often overlooked or not even considered. This issue is illustrated in this study through the example of (dihydro)phenanthrenes, a group of natural products present in yams, as AMP-activated protein kinase (AMPK) activators. A study conducted in our group on a series of compounds, fully characterized using a combination of chemical synthesis, NMR and MS techniques, provided evidence that the conclusions of a previous study were erroneous, likely due to the use of a misidentified commercial compound by its supplier. Furthermore, we demonstrated that additional representatives of the (dihydro)phenanthrene phytochemical classes were able to directly activate AMPK, avoiding the risk of misinterpretation of results based on analysis of a single compound alone.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425700","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}