Journal of Natural Products 最新文献

Total Synthesis and Structural Revision of (±)-Mauritamide B.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-21 DOI: 10.1021/acs.jnatprod.5c00019

Ryosuke Hirozumi, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

引用次数: 0

Menominin A and B: Cytotoxic Cyclodepsipeptides from the Freshwater Sponge-Associated Cyanobacterium Nostoc sp. UIC 10607.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-20 DOI: 10.1021/acs.jnatprod.4c01445

Lydia J Davis, Aleksej Krunić, Kelsey Alexander, Manead Khin, Jared S Wood, Cody Earp, Manuel Rangel-Grimaldo, Alessandra S Eustáquio, Joanna E Burdette, R Thomas Williamson, Nicholas H Oberlies, Jimmy Orjala

{"title":"Menominin A and B: Cytotoxic Cyclodepsipeptides from the Freshwater Sponge-Associated Cyanobacterium Nostoc sp. UIC 10607.","authors":"Lydia J Davis, Aleksej Krunić, Kelsey Alexander, Manead Khin, Jared S Wood, Cody Earp, Manuel Rangel-Grimaldo, Alessandra S Eustáquio, Joanna E Burdette, R Thomas Williamson, Nicholas H Oberlies, Jimmy Orjala","doi":"10.1021/acs.jnatprod.4c01445","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01445","url":null,"abstract":"Menominin A (1) and B (2), two cyclodepsipeptides containing a 3,8-dihydroxy-2-methyltetradecanoic acid residue, were isolated from the freshwater sponge-associated cyanobacterium, Nostoc sp. UIC 10607, using bioactivity-guided and spectroscopic approaches. The planar structures of 1 and 2 were established using HRESIMS and one- and two-dimensional NMR experiments. Comparative genomic analysis revealed unique differences in the putative menominin biosynthetic gene cluster compared to that of the closely related cyanobacterial cyclic lipodepsipeptide, hapalosin, assisting in structure elucidation and highlighting the structural diversity of this class of compounds. Configuration assignments were determined using a combination of J-based configuration analysis, chiral HPLC, modified Mosher's ester analysis, and DFT calculations. Menominin A and B demonstrate antiproliferative bioactivity against the high-grade serous ovarian cancer cell line OVCAR3 (IC50 = 3.1 (1) and 2.4 μM (2)). Menominin A and B are the first reported secondary metabolites from a freshwater sponge-associated cyanobacterium, underscoring the potential of freshwater sponges as a microbial culture source in natural product discovery.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466546","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

laeA Gene Introduction Strategy Enabling the Construction of a Prolific Fungal Secondary Metabolite Library.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-20 DOI: 10.1021/acs.jnatprod.4c01317

Aoi Kimishima, Sota Honma, Satoshi Kato, Masako Honsho, Hiroki Kojima, Toshiyuki Tokiwa, Akihiro Sugawara, Kenichi Nonaka, Yasuko Araki, Tadashi Takahashi, Kotaro Ito, Yukihiro Asami

{"title":"laeA Gene Introduction Strategy Enabling the Construction of a Prolific Fungal Secondary Metabolite Library.","authors":"Aoi Kimishima, Sota Honma, Satoshi Kato, Masako Honsho, Hiroki Kojima, Toshiyuki Tokiwa, Akihiro Sugawara, Kenichi Nonaka, Yasuko Araki, Tadashi Takahashi, Kotaro Ito, Yukihiro Asami","doi":"10.1021/acs.jnatprod.4c01317","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01317","url":null,"abstract":"LaeA is a putative nuclear methyltransferase protein that epigenetically influences secondary metabolite production in fungi. LaeA has drawn attention as one of the promising approaches to activate fungal chemical production, and the laeA gene has been introduced into some fungal strains with the aim of producing secondary metabolic changes mainly based on the evaluation of mycotoxicity. However, these studies were applied for limited fungal species, and its utility and versatility for broad fungal species remained unclear. In this study, 47 strains were selected composed of three different genera, Pochonia spp., Gamszarea kalimantanensis, and Lecanicillium spp., which have never been modified with the laeA gene. We obtained a total of 125 mutants with laeA genes for our fungal strain library. The chemical productivity and the biological activity of the library were analyzed, and two natural products, radicicol (1) and sch210972 (2), were isolated in more than 10-fold the yield of the parent strains.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456241","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

Characterization of an Iterative Halogenase Acting on Ribosomal Peptides Underlies the Combinatorial Biosynthesis Logic of Lasso Peptides.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-20 DOI: 10.1021/acs.jnatprod.4c01199

Jin-Long Lu, Jiao-Jiao Cui, Zhe-Yang Hu, Jin-Ming Di, Yuan-Yuan Li, Jiang Xiong, Yu-Meng Jiao, Kun Gao, Jian Min, Shangwen Luo, Shi-Hui Dong

{"title":"Characterization of an Iterative Halogenase Acting on Ribosomal Peptides Underlies the Combinatorial Biosynthesis Logic of Lasso Peptides.","authors":"Jin-Long Lu, Jiao-Jiao Cui, Zhe-Yang Hu, Jin-Ming Di, Yuan-Yuan Li, Jiang Xiong, Yu-Meng Jiao, Kun Gao, Jian Min, Shangwen Luo, Shi-Hui Dong","doi":"10.1021/acs.jnatprod.4c01199","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01199","url":null,"abstract":"Halogenation is commonly utilized in medicinal chemistry for the improvement of drug leads. Flavin-dependent halogenases (FDHs) are ubiquitous across all domains of life, yet iterative FDHs are rare in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs). Herein, we characterize a novel iterative FDH, ChlH, which orchestrates nonsequential chlorination of two specific Trp within the core peptide of a lasso precursor containing three Trp. Biochemical and computational studies enable the characterization of ChlH, which employs unique protein-peptide interactions (PPIs) between its distinct N- and C-terminal motifs and a crucial recognition sequence (RS-II) downstream of RS-I in the leader peptide. Previous studies have demonstrated the indispensability of RS-I for lasso peptide biosynthesis, while RS-II was considered to be replaceable. Furthermore, we find that the core peptide substantially contributes to the PPI. Bioinformatic analysis reveals the prevalence of homologous FDHs in the biosynthetic gene clusters (BGCs) of various RiPP classes. Heterologous expression of the chl BGC yields non-, mono-, and dichlorinated lasso peptides, with chlorination, particularly dichlorination, enhancing their antibacterial activity. This study expands the FDH activity spectrum to include iterative catalysis on ribosomal peptides and underscores the significance of RS-II in tailoring enzymes for the combinatorial biosynthesis of lasso peptides.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456244","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

Ohauamines A-D, Structurally Unprecedented Tricyclic Depsi-tripeptides from the New Zealand Ascidian Pycnoclavella kottae.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-20 DOI: 10.1021/acs.jnatprod.5c00033

Dan Chen, Florent Rouvier, Robert Keyzers, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Melissa M Cadelis, Brent R Copp

引用次数: 0

Secondary Metabolites of the Lichen Lethariella cladonioides and Their Neuroprotective Potential.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-18 DOI: 10.1021/acs.jnatprod.4c01359

Lei Zhang, Wen-Hua Chao, Cui-Cui Tan, Zhi-Ying Dou, Feng Qiu, Yu-Ming Liu, Jing-Jing Wang, Li-Ning Wang

{"title":"Secondary Metabolites of the Lichen Lethariella cladonioides and Their Neuroprotective Potential.","authors":"Lei Zhang, Wen-Hua Chao, Cui-Cui Tan, Zhi-Ying Dou, Feng Qiu, Yu-Ming Liu, Jing-Jing Wang, Li-Ning Wang","doi":"10.1021/acs.jnatprod.4c01359","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01359","url":null,"abstract":"In the pathogenesis of neurodegenerative diseases, particularly Alzheimer's disease, cholinergic neuron dysfunction and neuroinflammation are integral components. Against this backdrop, within the vast array of potential sources under exploration, Lethariella cladonioides, a remarkable lichen with profound ethnopharmacological significance among various Chinese ethnic minorities, has recently emerged as a promising candidate. Through our comprehensive phytochemical investigation, five undescribed diphenylmethanes (1-5), three unreported depsides (6-8), and one novel diphenylether (9), along with 16 known compounds, were successfully isolated and identified. Their structures were elucidated by spectroscopic analysis and X-ray crystallography. Specifically, compounds 3-7 and 9 exhibited acetylcholinesterase inhibitory activity, while compounds 1, 2, and 4 significantly inhibited NO production by LPS in RAW264.7 cells. Collectively, these findings suggest that L. cladonioides has potential value in preventing and treating neurodegenerative diseases. This potential lies in its ability to potentially retard disease progression or alleviate symptoms by enhancing cholinergic transmission and mitigating neuroinflammation.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439386","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 Furopyran Lignans Sumatranin A-D and the Proposed Structure of Sumatranin H.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-18 DOI: 10.1021/acs.jnatprod.4c01466

Zong Hao Jia, Lisa I Pilkington, David Barker

引用次数: 0

Isocoumarins from Spegazzinia sp. MDCW-573 with Antibacterial and Proangiogenic Activities.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-17 DOI: 10.1021/acs.jnatprod.4c01437

Cong Wang, Hui Xu, Jianjian Wang, Caixia Wei, Shengyan Zheng, Rui Xu, Shiyi Wang, Zilin Li, Peihai Li, Fandong Kong

{"title":"Isocoumarins from Spegazzinia sp. MDCW-573 with Antibacterial and Proangiogenic Activities.","authors":"Cong Wang, Hui Xu, Jianjian Wang, Caixia Wei, Shengyan Zheng, Rui Xu, Shiyi Wang, Zilin Li, Peihai Li, Fandong Kong","doi":"10.1021/acs.jnatprod.4c01437","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01437","url":null,"abstract":"Twelve new isocoumarins, spegazmarins A-L (1-12), including nine novel dimeric derivatives (1-9), three monomeric derivatives (10-12), as well as eight known ones (13-20), were isolated from the endophytic fungus Spegazzinia sp. MDCW-573. Their structures were elucidated by analysis of NMR, X-ray crystallography, and ECD data. Notably, the dimeric isocoumarins (1-9) possess a unique linkage, where the phenyl of one monomer is connected to the lactone of another. The methods for determining the configurations of both the monomeric and dimeric isocoumarins within this class were proposed, leading to the correction of the configurations of two previously reported isocoumarins. The isolated compounds inhibited Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with MIC values of 1 to 64 μg/mL. Compounds 5, 6, and 12 significantly promoted the growth of zebrafish intersegmental vessels at concentrations of 10, 20, and 40 μM, respectively.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439385","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

Pestones A and B from a Fungus Pestalotiopsis sp. Bound to Mutant p53 and Changed Its Conformation.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-14 DOI: 10.1021/acs.jnatprod.4c01440

Yusaku Sadahiro, Misaki Okubo, Yuki Hitora, Natsuko Hitora-Imamura, Shunsuke Kotani, Sachiko Tsukamoto

{"title":"Pestones A and B from a Fungus Pestalotiopsis sp. Bound to Mutant p53 and Changed Its Conformation.","authors":"Yusaku Sadahiro, Misaki Okubo, Yuki Hitora, Natsuko Hitora-Imamura, Shunsuke Kotani, Sachiko Tsukamoto","doi":"10.1021/acs.jnatprod.4c01440","DOIUrl":"10.1021/acs.jnatprod.4c01440","url":null,"abstract":"Oncogenic mutant p53 is one of the targets for cancer therapy, and the development of anticancer drugs that reactivate mutant p53 is a promising strategy. The extract of fungus Pestalotiopsis sp. changed mutant p53 to wild-type-like p53 in Saos-2 (p53R175H) cells, as shown by fluorescent immunostaining, and bioassay-guided purification of the extract afforded new dimeric epoxyquinoids, pestones A and B (1 and 2), and a known compound, rosnecatrone (3). The relative and absolute configurations of 1 and 2 were determined based on the spectroscopic data and semisynthesis from 3. Compounds 1 and 2 altered the conformation of mutant p53 in Saos-2 (p53R175H) cells, as shown by immunofluorescence staining. The cellular thermal shift assay analysis showed that 1 increased the thermostability of mutant p53 in Saos-2 (p53R175H) cells, suggesting the direct binding of 1 to mutant p53. Compounds 1 and 2 exhibited cytotoxic activities against Saos-2 (p53R175H) cells with IC50 values of 1.0 and 1.1 μM, respectively. Compound 1 was found to induce apoptosis in Saos-2 (p53R175H) cells by flow cytometry analysis and decreased tumor growth in vivo using a mouse model with HuCCT1 (p53R175H) cells.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424622","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

Anti-inflammatory and Hepatoprotective Iridoid Glycosides from the Roots of Gomphandra mollis.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-02-13 DOI: 10.1021/acs.jnatprod.4c01484

Quoc-Dung Tran Huynh, Thuy-Tien Thi Phan, Ta-Wei Liu, Thanh-Vu Nguyen, Truc-Ly Thi Duong, Su-Jung Hsu, Man-Hsiu Chu, Yun-Han Wang, Bien-Thuy Nguyen Bui, Dang-Khoa Nguyen, Thanh-Hoa Vo, Ching-Kuo Lee

{"title":"Anti-inflammatory and Hepatoprotective Iridoid Glycosides from the Roots of Gomphandra mollis.","authors":"Quoc-Dung Tran Huynh, Thuy-Tien Thi Phan, Ta-Wei Liu, Thanh-Vu Nguyen, Truc-Ly Thi Duong, Su-Jung Hsu, Man-Hsiu Chu, Yun-Han Wang, Bien-Thuy Nguyen Bui, Dang-Khoa Nguyen, Thanh-Hoa Vo, Ching-Kuo Lee","doi":"10.1021/acs.jnatprod.4c01484","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01484","url":null,"abstract":"Ten previously undescribed iridoid glycosides (1-10), including monoiridoids, hybrid iridoid-alkaloids, bis-iridoids, noriridoid-iridoid dimers, and tetramers, were isolated from the roots of Gomphandra mollis Merr. Structural elucidation revealed unique sugar chains not previously observed for iridoids and complex tetrameric configurations that are rare in nature. Compounds 9, 10, and 15 demonstrated significant anti-inflammatory effects, with IC50 values ranging from 6.13 to 13.0 μM, and compounds 6, 7, and 11-13 showed notable hepatoprotective activity in HepG2 cells. Additionally, structure-activity relationship (SAR) analysis on anti-inflammatory effects was also conducted. This study enriches the structural database of iridoids, particularly complex derivatives, and highlights their therapeutic potential in addressing inflammation-related and liver diseases.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412370","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