Won Min Lee, Si-Young Ahn, Gyu Sung Lee, InWha Park, Jonghwan Kim, Seung Hwan Lee, Sullim Lee, Chung Sub Kim
{"title":"Discovery and Biosynthesis of Indole-Functionalized Metabolites from the Human Blood Bacterium, <i>Paracoccus sanguinis</i>, and Their Anti-Skin Aging Activity.","authors":"Won Min Lee, Si-Young Ahn, Gyu Sung Lee, InWha Park, Jonghwan Kim, Seung Hwan Lee, Sullim Lee, Chung Sub Kim","doi":"10.1021/acs.jnatprod.4c01354","DOIUrl":"10.1021/acs.jnatprod.4c01354","url":null,"abstract":"<p><p>The human microbiome plays a crucial role in health and disease, with microbial metabolites acting as key mediators of physiological processes. While extensive research has focused on gut-derived microbes, the metabolic contributions of blood-derived bacteria remain underexplored. Here, we investigate the facultative anaerobe <i>Paracoccus sanguinis</i>, a Gram-negative bacterium isolated from human blood, and its metabolome, revealing insights into its potential impacts on health and disease. Using advanced analytical methods, we characterized 12 metabolites (<b>1</b>-<b>12</b>), including six novel compounds (<b>1</b>-<b>3</b>, <b>9</b>, <b>10</b>, and <b>12</b>). Biosynthetic studies demonstrated that these metabolites are derived through enzymatic and nonenzymatic pathways. Functional evaluations revealed significant antiaging activities for <b>1</b>, <b>6</b>, and <b>11</b> in TNF-α-stimulated normal human dermal fibroblasts (NHDFs), including suppression of reactive oxygen species (ROS), inhibition of matrix metalloproteinase-1 (MMP-1) secretion, and reduction of inflammatory cytokines interleukin (IL)-6 and IL-8. Among the tested compounds, <b>11</b> exhibited the highest antiaging efficacy, highlighting its potential as a candidate for therapeutic applications targeting skin aging. This study elucidates the biosynthetic pathways of <i>P. sanguinis</i> metabolites and their antiskin aging activity, underscoring their potential in modulating skin health and offering novel insights into the functional roles of blood-derived microbiota in human health.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1120-1129"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955063","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}
{"title":"Lyciumines A and B: Two Pyrrole-Fused Alkaloids from the Fruits of <i>Lycium barbarum</i>.","authors":"Yan-Jie Zhu, Xiang-Yang Dai, Yi-Lin Zhao, Yu-Guo Ma, Zhen-Zhu Zhao, Cheng-Fu Su, Zhi-You Hao, Dongdong Wang, Hui Chen","doi":"10.1021/acs.jnatprod.5c00385","DOIUrl":"10.1021/acs.jnatprod.5c00385","url":null,"abstract":"<p><p>Two novel pyrrole-fused alkaloids, lyciumines A (<b>1</b>) and B (<b>2</b>), were isolated from the fruits of <i>Lycium barbarum</i>. Their structures were elucidated by analysis of NMR spectroscopic and MS spectrometric data, along with computational studies. Compound <b>1</b> represents a novel pyrroloindoline alkaloid with a rare 6/5/5/6 tetracyclic system connected with a 2-formyl-5-methylpyrrole moiety via a C-C bond. Compound <b>2</b> features an unusual pyrrole alkaloid with a 5/5/5 tricyclic skeleton. Compound <b>1</b> significantly increases glucose consumption in insulin-resistant HepG2 cells in a dose-dependent manner. Further mechanism investigations demonstrated that compound <b>1</b> regulates glucose metabolism via activating the AMPK/PI3K/Akt signaling pathway.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1237-1243"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955064","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}
Qian Huang, Ni-Ping Li, Song Ang, Wei Huang, Jia-Qing Cao, Ji-Hong Gu, Lei Wang, Zhen-Long Wu, Wen-Cai Ye
{"title":"Dimeric Acylphloroglucinol Derivatives with Anti-MRSA Activities from <i>Chamelaucium uncinatum</i>.","authors":"Qian Huang, Ni-Ping Li, Song Ang, Wei Huang, Jia-Qing Cao, Ji-Hong Gu, Lei Wang, Zhen-Long Wu, Wen-Cai Ye","doi":"10.1021/acs.jnatprod.5c00163","DOIUrl":"10.1021/acs.jnatprod.5c00163","url":null,"abstract":"<p><p>Chamelauciumols A-I (<b>1</b>-<b>9</b>), nine undescribed dimeric acylphloroglucinol derivatives, were isolated from the aerial parts of <i>Chamelaucium uncinatum</i>. Structurally, compound <b>1</b> featured a new carbon skeleton characterized by an unprecedented prenyl-substituted methanodibenzo[<i>b</i>,<i>f</i>][1,5]dioxocin core. Compounds <b>2</b> and <b>3</b> represented new dimeric scaffolds, consisting of two methylated acylphloroglucinol derivatives linked via prenyl units. Compounds <b>4</b>-<b>9</b> were new phloroglucinol dimers with various linkage patterns. The structures and absolute configurations of these compounds were elucidated by comprehensive spectroscopic data, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculation. Besides, the antibacterial activities against Gram-positive and Gram-negative bacterial strains of the isolates were evaluated. Compounds <b>3</b> and <b>4</b> exhibited potent inhibitory effects against methicillin-resistant <i>Staphylococcus aureus</i> with minimum inhibitory concentration values ranging from 0.5 to 1 μg/mL. A preliminary study on the mechanism of action revealed that compounds <b>3</b> and <b>4</b> exerted anti-MRSA effects through disrupting bacterial cell membrane integrity. Additionally, compounds <b>3</b> and <b>4</b> also demonstrated remarkable antibiofilm activities.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1160-1171"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955517","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}
Yi Hua, Gangao Hu, Titi Ying, Jiangwei Pan, Zhenyi Zhou, Cuixian Zhang, Hong Wang, Bin Wei
{"title":"The Pathogenic Fungal Genus Corynespora: A Prolific Source of Bioactive Secondary Metabolites.","authors":"Yi Hua, Gangao Hu, Titi Ying, Jiangwei Pan, Zhenyi Zhou, Cuixian Zhang, Hong Wang, Bin Wei","doi":"10.1021/acs.jnatprod.5c00145","DOIUrl":"10.1021/acs.jnatprod.5c00145","url":null,"abstract":"<p><p>In this perspective, we examine the chemical structures and biological activities of 55 secondary metabolites isolated from the pathogenic fungal genus <i>Corynespora</i>. Over 20% of these compounds demonstrate bioactivities, including antibacterial, anticancer, enzyme inhibition, and others. Bioinformatic analysis reveals that <i>Corynespora</i> possesses a high potential for encoding PKS-I and NRPS natural products, including many clade-specific metabolites, and only 2.1% of biosynthetic gene cluster families are associated with known secondary metabolites. This study underscores the significant, unexplored potential of <i>Corynespora</i> strains for synthesizing novel secondary metabolites, providing valuable insights into the targeted discovery and biosynthesis of novel natural products from this genus.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1259-1269"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951459","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}
Sanket S Shete, Swetha Balamurugan, D Srinivasa Reddy
{"title":"Total Synthesis and Reconfirmation of the Absolute Configuration of (3<i>R</i>,4<i>S</i>)-6-Acetyl-3-hydroxy-7-methoxy-2,2-dimethylchroman-4-yl(<i>Z</i>)-2-methylbut-2-enoate Isolated from <i>Ageratina grandifolia</i>.","authors":"Sanket S Shete, Swetha Balamurugan, D Srinivasa Reddy","doi":"10.1021/acs.jnatprod.5c00269","DOIUrl":"10.1021/acs.jnatprod.5c00269","url":null,"abstract":"<p><p>Herein, we report the first total synthesis and confirmation of the absolute stereochemical configuration of a natural product isolated from <i>Ageratina grandifolia</i> as (3<i>R</i>,4<i>S</i>)-6-acetyl-3-hydroxy-7-methoxy-2,2-dimethylchroman-4-yl(<i>Z</i>)-2-methylbut-2-enoate. We have used readily available resorcinol as a starting material and well-established Jacobson's asymmetric epoxidation in achieving the total synthesis. During this process, we prepared its enantiomers and positional isomers, which may be useful for biological studies.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1218-1224"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953087","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}
{"title":"Heterologous Expression of the Fellutanine Biosynthetic Gene Cluster and Characterization of the Dual Prenylation of cyclo(l-Trp-l-Trp) by a Single DMATS Enzyme.","authors":"Wei-Peng Chen, Wei Lin, Wei Chen, Shu-Zhen Chen, Jian-Bin Xiao, Xing-Tong Chen, Chao Chen, Fan Cai, Ming-Liang Zhang, Qin Li, Huai-Dong Zhang, Li Li, Hui Zhang","doi":"10.1021/acs.jnatprod.4c01116","DOIUrl":"10.1021/acs.jnatprod.4c01116","url":null,"abstract":"<p><p>2,5-Diketopiperazines (2,5-DKPs) are recognized for their structural rigidity and diverse bioactivities, making them significant in drug discovery. However, the stereochemical complexity of 2,5-DKPs presents challenges in chemical synthesis, particularly concerning indole derivatives such as indole diketopiperazines (IDKPs). Prenylation and oxidation further diversify these structures, enhancing their bioactivity and membrane affinity. Despite recent advances, the biosynthetic pathways of IDKPs, especially those involving dual prenylation, remain inadequately understood. In this study, the fellutanine biosynthetic gene cluster from <i>Nannizzia fulva</i> was cloned and heterologously expressed in <i>Aspergillus nidulans</i>. A partially oxidized intermediate in the fellutanine biosynthetic pathway was characterized. The dimethylallyl tryptophan synthase (DMATS) enzyme FelB was shown to catalyze consecutive prenylations at two C-2 positions of cyclo(l-Trp-l-Trp) in both in vivo and in vitro assays. Additionally, comparative studies with the known DMATS enzyme OkaC revealed differences in the regioselectivity. Furthermore, the biprenylation mechanism of FelB and OkaC was elucidated through molecular docking and active site analysis.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1111-1119"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956549","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}
Jiaming Luo, Yaoyao Shen, Ke Liu, Li Li Hong, Ming Yang, Ning Li, Hai Deng, Hou-Wen Lin, Yongjun Zhou
{"title":"Biosynthesis of a <i>N</i>-Acetylated Tricyclic Carbazole with Antithrombotic Activity.","authors":"Jiaming Luo, Yaoyao Shen, Ke Liu, Li Li Hong, Ming Yang, Ning Li, Hai Deng, Hou-Wen Lin, Yongjun Zhou","doi":"10.1021/acs.jnatprod.5c00179","DOIUrl":"10.1021/acs.jnatprod.5c00179","url":null,"abstract":"<p><p>Tricyclic carbazoles are significant pharmacophores. Herein, heterologous expression of the carbazole-3,4-quinone (<b>1</b>) biosynthetic pathway in the chassis host <i>Streptomyces albus</i> J1074 yielded a previously chemosynthesized orthoquinone carbazole (<b>2</b>) and three new <i>N</i>-acetylated carbazoles (<b>3</b>-<b>5</b>). Their structures were established by a combination of HR-ESI-MS, NMR, and X-ray crystallographic analysis. Compound <b>2</b>, the deaminated precursor of <b>4</b> and <b>5</b>, was enzymatically synthesized, indicating the substrate tolerance of the key enzymes in the bacterial tricyclic-carbazole biosynthetic pathway. Mutagenetic analysis revealed an arylamine <i>N</i>-acetyltransferase homologous gene required for the production of compounds <b>3</b>-<b>5</b>. Bioactivity analysis using the zebrafish model demonstrated that compound <b>5</b> has significant antithrombotic activity, potentially by downregulating the genes involved in the platelet activation and coagulation cascade. These findings expand the natural strategies for structural diversification of the tricyclic carbazole alkaloids.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1172-1180"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952466","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}
Jia-Li He, Yu Wang, Xiang-Xi Yi, Yu-Man Gan, Yong-Hong Liu, Cheng-Hai Gao, Kai Liu, Meng Bai
{"title":"Bioactive Sesterterpenoids from the Mangrove-Derived <i>Aspergillus</i> sp. GXIMD 03023.","authors":"Jia-Li He, Yu Wang, Xiang-Xi Yi, Yu-Man Gan, Yong-Hong Liu, Cheng-Hai Gao, Kai Liu, Meng Bai","doi":"10.1021/acs.jnatprod.5c00182","DOIUrl":"10.1021/acs.jnatprod.5c00182","url":null,"abstract":"<p><p>Four novel sesterterpenoids, asperterpenoids Q-T (<b>1</b>-<b>4</b>), featuring a rare 5/7/(3)6/5 pentacyclic skeleton were isolated from the mangrove-derived fungus <i>Aspergillus</i> sp. GXIMD 03023 using an NMR-guided approach. Their structures and absolute configurations were determined by comprehensive spectroscopic analysis, including 1D/2D-NMR and HRESIMS, supplemented by experimental and ECD spectral matching, DFT-calculated <sup>13</sup>C NMR chemical shifts, and DP4plus probability analysis. Compounds <b>1</b>-<b>4</b> were screened for antibacterial activity and benign prostatic hyperplasia (BPH) inhibitory activity. Compound <b>1</b> showed weak activity against <i>Vibrio harveyi</i> and <i>Xanthomonas campestris</i>, with MIC values of 3.12 and 6.25 μg/mL, respectively. Compound <b>3</b> had significant inhibitory activity against BPH with an IC<sub>50</sub> value of 3.68 μM.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1201-1207"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952405","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}
{"title":"Asteltoxins I-T: Polyketides from a Plant Endophytic Strain of <i>Pochonia bulbillosa</i>.","authors":"Chun-Lun Qin, Zheng Li, Zi-Jian Huang, Jin-Ling Chang, Junjun Liu, Fang-Fang Duan, Xiaoyi Wei, Han-Li Ruan","doi":"10.1021/acs.jnatprod.5c00303","DOIUrl":"10.1021/acs.jnatprod.5c00303","url":null,"abstract":"<p><p>Asteltoxins I-T (<b>1</b>-<b>12</b>), 12 asteltoxin-type polyketides, together with four known analogues (<b>13</b>-<b>16</b>), were isolated from an endophytic fungus <i>Pochonia bulbillosa</i> KNI755. Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound <b>1</b> featured a tetrahydro-2<i>H</i>-pyran-linked asteltoxin heterodimer incorporating a clavatol unit. Compounds <b>2</b> and <b>3</b> demonstrated unique tetrahydro-1,4-oxazine-linked asteltoxin heterodimers comprising a diphenyl ether unit. Compounds <b>4</b>-<b>7</b> presented unusual 1,4-dioxane-linked asteltoxin heterodimers also containing a diphenyl ether unit. Compounds <b>1</b>-<b>7</b> were immunosuppressive against concanavalin A (ConA)-induced T cell proliferation and lipopolysaccharide (LPS)-induced B cell proliferation with EC<sub>50</sub> values ranging from 9.2 to 26 μM and from 6.3 to 27 μM, respectively. Compound <b>1</b> exhibited inhibitory activity against the HCT116 human cancer cell line with an IC<sub>50</sub> value of 10 μM.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1225-1236"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955892","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}
Carsten Wieder, Claudia Simon-Sánchez, Johannes C Liermann, Rainer Wiechert, Karsten Andresen, Eckhard Thines, Till Opatz, Anja Schüffler
{"title":"Allantofuranone Biosynthesis and Precursor-Directed Mutasynthesis of Hydroxylated Analogues.","authors":"Carsten Wieder, Claudia Simon-Sánchez, Johannes C Liermann, Rainer Wiechert, Karsten Andresen, Eckhard Thines, Till Opatz, Anja Schüffler","doi":"10.1021/acs.jnatprod.5c00197","DOIUrl":"10.1021/acs.jnatprod.5c00197","url":null,"abstract":"<p><p>Genome mining and heterologous reconstitution of biosynthetic genes in <i>Aspergillus oryzae</i> enabled elucidation of the hitherto elusive biosynthetic route that produces allantofuranone (<b>1</b>), a bioactive natural product originally isolated from <i>Allantophomopsis lycopodina</i>. The core non-ribosomal peptide synthetase (NRPS)-like enzyme AlfA of the <i>alf</i> BGC produces polyporic acid (<b>2</b>) from phenylpyruvic acid. In subsequent reactions, compound <b>2</b> is reductively dehydrated by the bifunctional enzyme AlfC and methylated by AlfD to produce terferol (<b>6</b>). In a final step, the quinol moiety of compound <b>6</b> is oxidatively cleaved and contracted by the aromatic ring cleavage dioxygenase AlfB. Using combinatorial biosynthesis, we were able to manipulate the biosynthetic route to yield hydroxylated pathway congeners, most notably the new natural products deoxyascocorynin (<b>10</b>), hydroxyterferol (<b>11</b>), and hydroxyallantofuranone (<b>12</b>).</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1191-1200"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956794","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}