Journal of Natural Products 最新文献_第9页

New Discorhabdin D Analogues from Latrunculia spp. Sponges 来自 Latrunculia 附属海绵的新 Discorhabdin D 类似物

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 DOI: 10.1021/acs.jnatprod.4c0103610.1021/acs.jnatprod.4c01036

Maria Orfanoudaki, Masoumeh Dalilian, Lin Du, Cindy H. Chau, William D. Figg, Barry R. O’Keefe* and Tanja Grkovic*,

引用次数: 0

Transcription Factor Engineering in Aspergillus nidulans Leads to the Discovery of an Orsellinaldehyde Derivative Produced via an Unlinked Polyketide Synthase Gene. 黑曲霉中的转录因子工程发现了一种通过非连接多酮合成酶基因产生的橙皮醛衍生物。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-27 DOI: 10.1021/acs.jnatprod.4c00483

Chris Rabot, Michelle F Grau, Ruth Entwistle, Yi-Ming Chiang, Yamilex Zamora de Roberts, Manmeet Ahuja, C Elizabeth Oakley, Clay C C Wang, Richard B Todd, Berl R Oakley

{"title":"Transcription Factor Engineering in Aspergillus nidulans Leads to the Discovery of an Orsellinaldehyde Derivative Produced via an Unlinked Polyketide Synthase Gene.","authors":"Chris Rabot, Michelle F Grau, Ruth Entwistle, Yi-Ming Chiang, Yamilex Zamora de Roberts, Manmeet Ahuja, C Elizabeth Oakley, Clay C C Wang, Richard B Todd, Berl R Oakley","doi":"10.1021/acs.jnatprod.4c00483","DOIUrl":"10.1021/acs.jnatprod.4c00483","url":null,"abstract":"Secondary metabolites are generally produced by enzymes encoded by genes within a biosynthetic gene cluster. Transcription factor genes are frequently located within these gene clusters. These transcription factors often drive expression of the other genes of the biosynthetic gene cluster, and overexpression of the transcription factor provides a facile approach to express all genes within a gene cluster, resulting in production of downstream metabolite(s). Unfortunately this approach is not always successful, leading us to engineer more effective hybrid transcription factors. Herein, we attempted to activate a putative cryptic biosynthetic gene cluster in Aspergillus nidulans using a combination of transcription factor engineering and overexpression approaches. This resulted in the discovery of a novel secondary metabolite we term triorsellinaldehyde. Surprisingly, deletion of the polyketide synthase gene within the gene cluster did not prevent triorsellinaldehyde production. However, targeted deletion of a polyketide synthase gene elsewhere in the genome revealed its role in triorsellinaldehyde biosynthesis.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2384-2392"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mass Spectrometry Imaging of Coniine and Other Hemlock Alkaloids after On-Tissue Derivatization Reveals Distinct Alkaloid Distributions in the Plant. 组织衍生化后的柯尼碱和其他铁杉生物碱质谱成像揭示了植物中不同的生物碱分布。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-06-21 DOI: 10.1021/acs.jnatprod.4c00445

Diana A Barrera-Adame, Sabine Schuster, Timo H J Niedermeyer

{"title":"Mass Spectrometry Imaging of Coniine and Other Hemlock Alkaloids after On-Tissue Derivatization Reveals Distinct Alkaloid Distributions in the Plant.","authors":"Diana A Barrera-Adame, Sabine Schuster, Timo H J Niedermeyer","doi":"10.1021/acs.jnatprod.4c00445","DOIUrl":"10.1021/acs.jnatprod.4c00445","url":null,"abstract":"Specialized metabolites play important roles in plants and can, for example, protect plants from predators or pathogens. Alkaloids, due to their pronounced biological activity on higher animals, are one of the most intriguing groups of specialized metabolites, and many of them are known as plant defense compounds. Poison hemlock, Conium maculatum, is well-known for its high content of piperidine alkaloids, of which coniine is the most famous. The distribution, localization, and diversity of these compounds in C. maculatum tissues have not yet been studied in detail. The hemlock alkaloids are low molecular weight compounds with relatively high volatility. They are thus difficult to analyze on-tissue by MALDI mass spectrometry imaging due to delocalization, which occurs even when using an atmospheric pressure ion source. In this manuscript, we describe an on-tissue derivatization method that allows the subsequent determination of the spatial distribution of hemlock alkaloids in different plant tissues by mass spectrometry imaging. Coniferyl aldehyde was found to be a suitable reagent for derivatization of the secondary amine alkaloids. The imaging analysis revealed that even chemically closely related hemlock alkaloids are discretely distributed in different plant tissues. Additionally, we detected a yet undescribed hemlock alkaloid in Conium maculatum seeds.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2376-2383"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prorocentin-5: A Cytotoxic Polyketide from the Benthic Marine Dinoflagellate Prorocentrum lima. Prorocentin-5：一种来自底栖海洋双鞭毛藻 Prorocentrum lima 的细胞毒性多酮。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-10-08 DOI: 10.1021/acs.jnatprod.4c00851

Yunseok Choi, Eun Ju Jeong, Yeong Du Yoo, Jaeyeon Park, Jung-Rae Rho

引用次数: 0

Derivatization of Microcystins Can Increase Target Inhibition while Reducing Cellular Uptake. 微囊藻毒素的衍生物化可以增加对目标的抑制作用，同时减少细胞的吸收。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-20 DOI: 10.1021/acs.jnatprod.4c00688

Laura L Sallandt, Clemens A Wolf, Sabine Schuster, Heike Enke, Dan Enke, Gerhard Wolber, Timo H J Niedermeyer

{"title":"Derivatization of Microcystins Can Increase Target Inhibition while Reducing Cellular Uptake.","authors":"Laura L Sallandt, Clemens A Wolf, Sabine Schuster, Heike Enke, Dan Enke, Gerhard Wolber, Timo H J Niedermeyer","doi":"10.1021/acs.jnatprod.4c00688","DOIUrl":"10.1021/acs.jnatprod.4c00688","url":null,"abstract":"Microcystins, a large family of nonribosomal cyclic heptapeptides known for their hepatotoxicity, are among the best-studied cyanobacterial toxins. Recently, they have been discussed as leads for the development of anticancer drug substances. Their main mode-of-action is inhibition of the eukaryotic serine/threonine protein phosphatases 1 and 2A. Unlike many cytotoxins that can cross cell membranes by passive diffusion, microcystins depend on active uptake via organic anion transporting polypeptides 1B1 or 1B3. Both phosphatase inhibition and transportability strongly depend on the structure of the individual microcystin. Here, we present how chemical modification of positions 2 and 4 of the microcystin core structure can alter these two properties. Aiming to reduce transportability and increase phosphatase inhibition, we used pharmacophore modeling to investigate the phosphatase inhibition potential of microcystins derivatized with small molecules containing a variety of functional groups. The respective derivatives were synthesized using click chemistry. We discovered that some derivatized microcystins can address a yet undescribed subpocket of the protein phosphatase 1. The derivatized microcystins were tested for phosphatase 1 inhibition and cytotoxicity on transporter-expressing cell lines, revealing that target inhibition and transportability of microcystins can independently be influenced by the physicochemical properties, especially of the residue located in position 2 of the microcystin. Derivatization with small acids or amino acids resulted in microcystins with a favorable ratio of inhibition to transportability, making these derivatives potentially suitable for drug development.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted Discovery of a Natural ortho-Quinone Methide Precursor and Green Generation of Its Oligomers. 天然原醌甲醚前体的靶向发现及其低聚物的绿色生成。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-09-27 Epub Date: 2024-08-28 DOI: 10.1021/acs.jnatprod.4c00035

Xiao-Xia Wang, Bei-Qian Deng, Zhi-Qiu Ouyang, Yang Yan, Jian-Ming Lv, Sheng-Ying Qin, Dan Hu, Guo-Dong Chen, Xin-Sheng Yao, Hao Gao

{"title":"Targeted Discovery of a Natural ortho-Quinone Methide Precursor and Green Generation of Its Oligomers.","authors":"Xiao-Xia Wang, Bei-Qian Deng, Zhi-Qiu Ouyang, Yang Yan, Jian-Ming Lv, Sheng-Ying Qin, Dan Hu, Guo-Dong Chen, Xin-Sheng Yao, Hao Gao","doi":"10.1021/acs.jnatprod.4c00035","DOIUrl":"10.1021/acs.jnatprod.4c00035","url":null,"abstract":"ortho-Quinone methides (o-QMs) are a class of highly reactive intermediates that serve as important nonisolable building blocks (NBBs) in organic synthesis and small-molecule library construction. Because of their instability and nonisolability, most reported o-QMs are generated through in situ chemical synthesis, and only a few natural o-QMs have been reported due to the lack of directed discovery strategies. Herein, a new natural o-QM precursor (trichophenol A, 2) was identified from the fungal strain of Trichoderma sp. AT0167 through genome mining, which was generated by trilA (nonreducing polyketide synthase) and trilB (2-oxoglutarate dependent dioxygenase). Combinatorial biosynthesis via two other known NRPKS genes with trilA and trilB was performed, leading to the generation of five new trichophenol o-QM oligomers (trichophenols D-H, 5-9). The strategy combining genome mining with combinatorial biosynthesis not only targetedly uncovered a new natural o-QM precursor but also produced various new molecules through oligomerization of the new o-QM and its designated o-QM acceptors without chemical synthesis and isolation of intermediates, which was named NBB genome mining-combinatorial biosynthesis strategy for o-QM molecule library construction. This study provides a new strategy for the targeted discovery of natural o-QMs and small-molecule library construction with natural o-QMs.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2139-2147"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fungal Coculture of Herpotrichia sp. and Trametes versicolor Induces Production of Diverse Metabolites with Anti-Parkinson's Neuroprotective Activity. Herpotrichia sp.和Trametes versicolor真菌共培养诱导产生具有抗帕金森氏症神经保护活性的多种代谢产物

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-09-27 Epub Date: 2024-08-30 DOI: 10.1021/acs.jnatprod.4c00421

Zi-Jue Wang, Yi-Rui Hong, Xin-Yu Wang, Jing-Zhe Wang, Yi-Jie Zhai, Wei Cui, Wen-Bo Han

{"title":"Fungal Coculture of Herpotrichia sp. and Trametes versicolor Induces Production of Diverse Metabolites with Anti-Parkinson's Neuroprotective Activity.","authors":"Zi-Jue Wang, Yi-Rui Hong, Xin-Yu Wang, Jing-Zhe Wang, Yi-Jie Zhai, Wei Cui, Wen-Bo Han","doi":"10.1021/acs.jnatprod.4c00421","DOIUrl":"10.1021/acs.jnatprod.4c00421","url":null,"abstract":"Co-cultivation of isopod-associated fungi Herpotrichia sp. SF09 and Trametes versicolor SF09A led to the reciprocal induction of thirteen new compounds (1-7 and 9-13) with diverse architectures. Importantly, compounds 1 and 2 are rare fungal sesquiterpene-saccharide hybrids incorporating a xylopyranose moiety, compound (±)-3 represents the first example of a natural linear sesquiterpene racemate, and compound 7 is a rare α-pyrone derivative with a xylopyranose motif. Their structures were elucidated by analysis of NMR and mass spectrometry data, and their absolute configurations were determined by Mosher's method, microscale derivatization, and single-crystal X-ray diffraction, as well as ECD calculations. All the isolated compounds ameliorated MPP+-induced oxidative damage in PC12 cells in a dose-dependent fashion. Among them, compounds 5 and 15 showed significant protective action against neuronal injury by MPP+ at 5 μM. Meanwhile, transcriptome sequencing was performed to evaluate the molecular mechanism of the neuroprotective activity for compound 5. Results indicated that compound 5 might mitigate MPP+-induced neuronal injury through the regulation of multiple signaling pathways, including the PI3K-Akt and MAPK pathways. Our findings suggested that compound 5 could be a promising neuroprotective agent for the treatment of Parkinson's disease.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2180-2193"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Total Synthesis of the Dimeric Phytocannabinoid Cannabitwinol (CBD Dimer) and Its Analogues. 二聚植物大麻素 Cannabitwinol（CBD 二聚体）及其类似物的全合成。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-09-27 Epub Date: 2024-08-26 DOI: 10.1021/acs.jnatprod.4c00674

Sanket S Shete, Anup Kumar Mondal, D Srinivasa Reddy

引用次数: 0

Undescribed Amaryllidaceae Alkaloids from Zephyranthes citrina and Their Cytotoxicity. 来自 Zephyranthes citrina 的未被描述的 Amaryllidaceae 生物碱及其细胞毒性。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-09-27 Epub Date: 2024-09-04 DOI: 10.1021/acs.jnatprod.4c00825

Jana Křoustková, Eliška Kohelová, Darina Muthná, Jiří Kuneš, Radim Havelek, Rudolf Vrabec, Milan Malaník, Daniela Suchánková, Jakub Chlebek, Jaroslav Jenčo, Štefan Kosturko, Lucie Cahlíková

{"title":"Undescribed Amaryllidaceae Alkaloids from Zephyranthes citrina and Their Cytotoxicity.","authors":"Jana Křoustková, Eliška Kohelová, Darina Muthná, Jiří Kuneš, Radim Havelek, Rudolf Vrabec, Milan Malaník, Daniela Suchánková, Jakub Chlebek, Jaroslav Jenčo, Štefan Kosturko, Lucie Cahlíková","doi":"10.1021/acs.jnatprod.4c00825","DOIUrl":"10.1021/acs.jnatprod.4c00825","url":null,"abstract":"This phytochemical study presents the isolation of eight alkaloids from Zephyranthes citrina Baker. The structures of the new alkaloids, zephycitrine (1) and 6-oxonarcissidine (2), were established by analysis of spectroscopic and spectrometric data. Processing the EtOH extract under acid-base conditions yielded the unreported isolation artifacts 3 and 4. This work also provides analytical data for alkaloids not properly described in the literature (5 and 6). The hippeastidine/zephyranine scaffolds in derivatives 3, 4, and 8-10 are also thoroughly discussed. Furthermore, a cytotoxicity screening of 25 Amaryllidaceae alkaloids isolated from Z. citrina was performed. Only the known alkaloids haemanthamine (12), haemanthidine (13), and lycorine (27) showed significant cell growth inhibition.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2317-2326"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Natural Rubrolides and Their Synthetic Congeners as Inhibitors of the Photosynthetic Electron Transport Chain. 作为光合作用电子传递链抑制剂的天然茜草内酯及其合成同系物。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-09-27 Epub Date: 2024-09-06 DOI: 10.1021/acs.jnatprod.4c00714

Milandip Karak, Jaime A M Acosta, Héctor F Cortez-Hernandez, Johnny L Cardona, Giuseppe Forlani, Luiz C A Barbosa

{"title":"Natural Rubrolides and Their Synthetic Congeners as Inhibitors of the Photosynthetic Electron Transport Chain.","authors":"Milandip Karak, Jaime A M Acosta, Héctor F Cortez-Hernandez, Johnny L Cardona, Giuseppe Forlani, Luiz C A Barbosa","doi":"10.1021/acs.jnatprod.4c00714","DOIUrl":"10.1021/acs.jnatprod.4c00714","url":null,"abstract":"Rubrolides are a family of naturally occurring 5-benzylidenebutenolides, which generally contain brominated phenol groups, and nearly half of them also present a chlorine attached to the butenolide core. Seven natural rubrolides were previously synthesized. When these compounds were tested against the model plant Raphanus sativus, six were found to exert a slight inhibition on plant growth. Aiming to exploit their scaffold as a model for the synthesis of new compounds targeting photosynthesis, nine new rubrolide analogues were prepared. The synthesis was accomplished in 2-4 steps with a 10-39% overall yield from 3,4-dichlorofuran-2(5H)-one. All compounds were evaluated for their ability to inhibit the whole Hill reaction or excluding photosystem I (PSI). Several natural rubrolides and their analogues displayed good inhibitory potential (IC50 = 2-8 μM). Molecular docking studies on the photosystem II-light harvesting complex II (PSII-LHCII supercomplex) binding site were also performed. Overall, data support the use of rubrolides as a model for the development of new active principles targeting the photosynthetic electron transport chain to be used as herbicides.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2272-2280"},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0