Natural Products and Bioprospecting最新文献

{"title":"Revolutionizing microbial treasure troves: innovative strategies for natural products discovery","authors":"Yu-Jie Li,&nbsp;Ming-Hua Qiu,&nbsp;Xing-Rong Peng","doi":"10.1007/s13659-025-00565-0","DOIUrl":"10.1007/s13659-025-00565-0","url":null,"abstract":"<div><p>Microorganisms represent Earth's most abundant biological resource, producing metabolites of immense value across medicine, agriculture, and industry. Conventional cultivation and screening techniques, however, suffer from inefficiency and fail to meet contemporary demands. Providing a comprehensive overview, this review details how the One Strain Many Compounds (OSMAC) strategy—addressing cultivation bottlenecks—and genomics-driven mining approaches are revolutionizing the discovery of novel microbial metabolites. Crucially, it underscores the broad adoption of innovative technologies like machine learning to enable faster, more effective gene and structure targeting. Synthesizing case studies from 2019 to 2025, the review catalogs newly identified compounds and their bioactivities, while outlining future research directions to establish a theoretical framework for efficient microbial natural product exploration. These advanced discovery strategies are significantly accelerating the identification of structurally diverse lead compounds with novel mechanisms of action, thereby revitalizing pipelines for new antibiotic, anticancer, and therapeutic drug development.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00565-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mevalonic acid exerts procoagulant effect by potentiating factor Xa","authors":"Liyuan Niu,&nbsp;Chuanfeng Liu,&nbsp;Shaoying Wang,&nbsp;Qikai Yin,&nbsp;Shiping Lin,&nbsp;Musan Yan,&nbsp;Wenshuo Li,&nbsp;Yuanjie Yin,&nbsp;Wei Wang,&nbsp;Wenjuan Yu,&nbsp;Xiaopeng Tang,&nbsp;Min Xue,&nbsp;Yuewei Wang","doi":"10.1007/s13659-025-00564-1","DOIUrl":"10.1007/s13659-025-00564-1","url":null,"abstract":"<div><p>Thrombosis pathogenesis is closely linked to dysregulated lipid metabolism and inflammatory processes. However, the direct regulatory role of mevalonate pathway within the coagulation cascade is still not well understood. This study aimed to elucidate the regulatory effects of mevalonic acid (MVA) on the coagulation system. The effects of MVA on coagulation were measured by recalcification. Enzymatic kinetic analysis and natural substrate hydrolysis assays were performed to identify the coagulation target of MVA. Mice bleeding and thrombosis models were applied to evaluate the effects of MVA administration on hemostasis and thrombosis. Our current study reveals that MVA significantly accelerates plasma coagulation through potentiating the procoagulant activity of FXa, without influencing the platelet aggregation. Studies showed that MVA administration substantially shortened activated partial thromboplastin time, prothrombin time, and reduced bleeding time in both tail bleeding and saphenous vein injury models. Furthermore, using ferric chloride-induced thrombosis, deep vein thrombosis and cerebral infarction models, we observed that MVA markedly potentiated thrombus formation and stroke. Our findings establish for the first time that MVA directly regulates FXa procoagulant activity, while also suggesting potential crosstalk between lipid metabolic pathways and inflammatory signaling in coagulation modulation. These results provide novel mechanistic insights into coagulation abnormalities associated with metabolic disorders such as atherosclerosis and diabetes, highlighting the mevalonate pathway as a potential therapeutic target for thrombotic complications.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00564-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the metabolic potential and roles of reductases in the omicsynin biosynthetic gene cluster","authors":"Yihong Li,&nbsp;Jie Fu,&nbsp;Hongmin Sun,&nbsp;Yu Du,&nbsp;Shuyi Si,&nbsp;Yuhuan Li,&nbsp;Xingxing Li,&nbsp;Jiandong Jiang,&nbsp;Bin Hong","doi":"10.1007/s13659-025-00560-5","DOIUrl":"10.1007/s13659-025-00560-5","url":null,"abstract":"<div><p>Omicsynins are a group of pseudo-tetrapeptides produced by <i>Streptomyces</i> sp. 1647, which exhibited potent anti-influenza A virus and anti-coronavirus activities. However, its biosynthesis mechanism of C-terminus reduction remains unknown. In this work, we explored two short-chain dehydrogenase/reductase (SDR) superfamily encoding genes in the omicsynin biosynthetic gene cluster (BGC) and confirmed the necessity of <i>omnF</i>, rather than <i>omnG</i>, in the biosynthesis of omicsynins through gene deletion in vivo. Subsequently, Feature-Based Molecular Networking (FBMN) analysis revealed three pseudo-tetrapeptides with C-terminal carboxyl group and four unexpected analogues encoded by the omicsynin BGC in the <i>omnF</i> reductase (R) domain knockout mutant strain. This led to the isolation and structural characterization of a group of novel pseudo-tripeptide compounds. Compared to the known omicsynins, these pseudo-tripeptides lack the second amino acid unit and the C-terminal aldehyde group, and consequently lose their anti-coronavirus activity. In conclusion, our work highlights the effectiveness of FBMN in unveiling cryptic analogues and clearly underscores the essential role of the R domain of OmnF in the biosynthesis of the C-terminal aldehyde warhead.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00560-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel triterpenoids from Ganoderma resinaceum attenuate UV-induced photoaging via modulating Nrf2 and MAPK signaling pathways","authors":"Yi Luo,&nbsp;Xiao-Cui Liu,&nbsp;Yu-Jie Li,&nbsp;Ming-Hua Qiu,&nbsp;Xing-Rong Peng","doi":"10.1007/s13659-025-00558-z","DOIUrl":"10.1007/s13659-025-00558-z","url":null,"abstract":"<div><p>As a dual-purpose medicinal and edible mushroom, <i>Ganoderma</i> species have garnered significant interest in both the food, cosmetics and pharmaceutical industries. To further substantiate its traditional and functional uses, we conducted a systematic phytochemical study of <i>Ganoderma resinaceum</i> fruiting bodies, isolating 43 lanostane-type triterpenoids. Among these, 16 were identified as new compounds (<b>1</b>–<b>11</b>, <b>15</b>, <b>31</b>, <b>35</b>, <b>37</b>, and <b>42</b>). Compound <b>1</b> represents the first reported C₂₉ lanostane triterpenoid featuring a 21,24-cyclo five membered carbon ring fraction. The spectroscopic (1D/2D NMR, ESIMS) and X-ray crystallographic analyses confirmed their structures. Among these, compounds <b>2</b>–<b>4</b>, <b>13</b>, <b>17</b>, <b>35</b>, <b>36</b>, and <b>42</b> exhibited potent antioxidant activity by suppressing UV-induced ROS in skin keratinocytes. The most active compound, <b>42</b>, reduced ROS and malondialdehyde (MDA) levels, enhanced antioxidant defenses (superoxide dismutase, SOD; hydroxyproline), and suppressed matrix metalloproteinases (MMPs) through activating Nrf2 pathway and suppressing MAPK signaling. These results position <i>G. resinaceum</i> triterpenoids, particularly compound <b>42</b>, as multifunctional natural antioxidants with applications in functional foods for oxidative stress management or skin-protective formulations.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00558-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panunoids A – D, four new prenylhydroquinone derivatives isolated from the fungus Panus rudis","authors":"Yun Liu,&nbsp;Jian-Qiang Zhao,&nbsp;Yan-Long Yang,&nbsp;Han-Bing Yuan,&nbsp;Yan-Ming Wang,&nbsp;Jun Yuan","doi":"10.1007/s13659-025-00562-3","DOIUrl":"10.1007/s13659-025-00562-3","url":null,"abstract":"<div><p>A chemical constituent study on the fermented rice substrate of basidiomycetous fungus <i>Panus rudis</i> led to the isolation of four previously undescribed prenylhydroquinone derivatives compounds (<b>1</b>–<b>4</b>) and eight known compounds (<b>5</b>–<b>12</b>). Among them, compound <b>3</b> featured a rare benzothiazole derivative with hydroxy substituted 3-methyl-1-butenyl substitution on the benzene ring, and the absolute configurations of <b>7</b> and <b>12</b> were elucidated as unreported ones. Their structures were identified by the interpretation of 1D and 2D NMR spectroscopy, HRESIMS data, X-ray single-crystal diffraction, and comparison of calculated and experimental ECD spectra. The plausible biosynthetic pathways for <b>1</b>–<b>7</b> are proposed. Cytotoxicity evaluation was conducted on <b>1</b> and <b>3</b>–<b>12</b> against two cancer cell lines (A-549 and HepG2). The results demonstrated that <b>1</b>, <b>3</b>–<b>6</b>, <b>8</b>, <b>9</b>, and <b>12</b> exhibited weak cytotoxicity against both two cell lines. Among them, <b>8</b> and <b>12</b> showed dose-dependent inhibitory effects, and their IC₅₀ values at 72 h were obtained.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00562-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-obesity Effects of Panax ginseng-derived exosomes via AMPK-mediated inhibition of adipocyte differentiation and lipogenesis","authors":"Min Ho Han,&nbsp;Sun Hye Lee,&nbsp;Youn Seon Hwang,&nbsp;Jong Hyun Oh,&nbsp;Jin Woo Kim","doi":"10.1007/s13659-025-00561-4","DOIUrl":"10.1007/s13659-025-00561-4","url":null,"abstract":"<div><p>This study investigated the anti-obesity potential of <i>Panax ginseng</i>-derived exosomes (PGE) by evaluating their influence on energy metabolism, adipogenesis, and lipid accumulation. PGEs were isolated using a tangential flow filtration system, yielding particles with an average diameter of 159.5 nm and a concentration of 3.9 × 10¹² particles/mL. In 3T3-L1 preadipocytes, PGE treatment resulted in a 72.1% reduction in lipid accumulation, as demonstrated by Oil Red O staining, indicating significant inhibition of adipogenic differentiation. Elevated expression of surface markers TET-8 (147.2%) verified the exosomal nature of the isolated vesicles. To determine their role in adipocyte differentiation, we analyzed gene and protein expression of key adipogenic markers–peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer-binding protein alpha and beta, and fatty acid-binding protein 4-revealing reductions of 23.6–35.6% and 26.7–35.2%, respectively. These results indicate downregulation of transcriptional and translational pathways driving adipogenesis. Lipogenic regulators, including sterol regulatory element-binding protein 1c, acetyl-CoA carboxylase, and fatty acid synthase, were also suppressed by 24.9–41.0% (gene) and 22.8–24.5% (protein), indicating impaired fatty acid synthesis. Conversely, AMP-activated protein kinase (<i>AMPK)</i> expression increased by up to 53.8% (gene) and 47.9% (protein), implying activation of energy homeostasis signaling. Immunofluorescence analysis showed a reduction in the MitoTracker/DAPI ratio (57.7–60.0%) and an increase in the F-actin/DAPI ratio (39.5–60.8%), indicating decreased mitochondrial activity and enhanced cytoskeletal integrity. These molecular changes were accompanied by AMPK activation and PPAR-γ inhibition. Collectively, these findings underscore the potential of PGEs as bioactive agents for obesity management by concurrently inhibiting adipogenesis and lipogenesis, providing a strong basis for their application in anti-obesity functional foods and pharmaceutical products.</p><h3>Graphic Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00561-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aglodorols A–J, undescribed terpenoids with multidimensional neuroprotective activities from Aglaia odorata Lour.","authors":"Meng Ding,&nbsp;Yue-Han Wang,&nbsp;Chen-Hao Liu,&nbsp;Wang-Xiao Tan,&nbsp;Li-Ming Hu,&nbsp;Ke-Wu Zeng,&nbsp;Peng-Fei Tu,&nbsp;Yong Jiang","doi":"10.1007/s13659-025-00563-2","DOIUrl":"10.1007/s13659-025-00563-2","url":null,"abstract":"<div><p>Three unprecedented triterpenoids (<b>1</b>–<b>2</b>, <b>8</b>), seven novel diterpenoids (<b>13</b>–<b>16</b>, <b>19</b>–<b>21</b>), and 12 known compounds (<b>3</b>–<b>7</b>, <b>9</b>–<b>12</b>, <b>17</b>–<b>18</b>, <b>22</b>) were isolated from the tender branches and leaves of <i>Aglaia odorata</i> Lour. Structural elucidation was achieved through integrated spectroscopic analysis, quantum chemical calculations (NMR/ECD), and single-crystal X-ray diffraction. All isolates were evaluated for neuroprotective effects. Compounds <b>3</b>, <b>9</b>–<b>11</b>, <b>13</b>, <b>17</b>, and <b>18</b> showed significant protective effects against oxygen-glucose deprivation/reperfusion (OGD/R)-mediated nerve injury in PC12 cells at 10 µM, while compounds <b>3</b> and <b>19</b> exhibited potent anti-excitotoxicity activity in the L-glutamate-induced HT22 cells at 20 µM. Strikingly, triterpenoids<b> 1</b>,<b> 2</b>, and <b>11</b> displayed remarkable activity against RSL3-induced PC12 cell death with EC₅₀ values ranging from 1.16 to 1.74 μM. Compound <b>22</b> exhibited the most significant inhibitory activity among the isolates against nitric oxide (NO) release in lipopolysaccharide (LPS)-activated BV2 cells with an IC₅₀ value of 22.41 µM.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00563-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics reveal how strong water binding naturally enhances wheat seed longevity and Fusarium resistance","authors":"Lorenzo Goglia,&nbsp;Vito Campanella,&nbsp;Agata Rascio","doi":"10.1007/s13659-025-00559-y","DOIUrl":"10.1007/s13659-025-00559-y","url":null,"abstract":"<div><p>Seed water content affects wheat quality, storage, and food safety, influencing viability and fungal contamination risks. Grain moisture is influenced by both genetic and environmental factors, with agronomic practices aiming to optimize it. However, no genotype has been specifically developed for enhanced seed water properties, as the underlying biochemical and genetic mechanisms remain unclear. Using a durum wheat mutant (WM) with higher water affinity of leaves, compared to its wild-type cultivar, Trinakria (WT), this study investigates the biophysical and biochemical mechanisms affecting seed performance. Genotypic characterization of unaged seeds includes differential scanning calorimetry, metabolomic profiling, and functional analyses of water uptake rate, dehydration rate, and seed coat electrical resistance. Germination and <i>Fusarium</i> resistance were examined, too in both unaged and aged seeds. As for the leaves, WM seeds exhibit higher water-binding strength than WT. Metabolomic analysis revealed a higher polar/apolar ratio in WM (83 vs. 72 in WT), with significantly greater myo-inositol and raffinose content and lower levels of unsaturated fatty acids. No differences in seed imbibition velocity or dehydration velocity were observed, but WM showed lower seed coat electrical resistance, indicating greater free water retention on the seed surface. Under low <i>Fusarium</i> inoculum concentrations or in the absence of pathogens, aged WM seeds showed higher germination rates and vigor than WT. As an inherited trait, selecting for strong water-binding capacity, increased osmoprotective compounds, and lower unsaturated acid content could contribute sustainably improve seed longevity and <i>Fusarium</i> resistance.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00559-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse phloroglucinols with hAChE inhibitory and anti-VRE effects from Rhodomyrtus tomentosa fruits","authors":"Ling-Yun Chen,&nbsp;Mu-Yuan Yu,&nbsp;E-E Luo,&nbsp;Wen-Ying Zong,&nbsp;Shu-Mei Lei,&nbsp;Yu Pan,&nbsp;Ai-Chun Lu,&nbsp;Cheng-Qin Liang,&nbsp;Xu-Jie Qin","doi":"10.1007/s13659-025-00557-0","DOIUrl":"10.1007/s13659-025-00557-0","url":null,"abstract":"<div><p><i>Rhodomyrtus tomentosa</i> fruits serve as both functional food and medicinal resources due to their rich bioactive constituents and manifold pharmacological effects. Phytochemical exploration of the <i>R. tomentosa</i> fruits led to the identification of eight new polymethylated phloroglucinols, designated as rhodotomentodione F (<b>1</b>) and rhodotomentodimers H‒N (<b>2</b>‒<b>8</b>), along with six previously described congeners (<b>9</b>‒<b>14</b>). Based on the detailed inspection of comprehensive spectroscopic data, electronic circular dichroism (ECD) simulations, and nuclear magnetic resonance (NMR) calculations, and DP4+ analyses, the structures of phloroglucinols <b>1</b>‒<b>8</b> were determined. Heterodimeric phloroglucinols <b>3</b>‒<b>14</b> exhibited human acetylcholinesterase (<i>h</i>AChE) inhibitory activities, with <b>13</b> exhibiting the highest potency (IC₅₀ = 1.04 μM). Moreover, molecular docking analysis clarified the potential binding interactions between the most active phloroglucinol <b>13</b> with <i>h</i>AChE. In addition, phloroglucinols <b>11</b> and <b>12</b> displayed significant anti-VRE (vancomycin-resistant <i>Enterococci</i>) activities, with MIC values reaching as low as 1 μg/mL.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00557-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in natural product discovery: strategies, technologies, and insights","authors":"Buddha Bahadur Basnet,&nbsp;Zhen-Yi Zhou,&nbsp;Rajesh Basnet,&nbsp;Bin Wei,&nbsp;Hong Wang","doi":"10.1007/s13659-025-00556-1","DOIUrl":"10.1007/s13659-025-00556-1","url":null,"abstract":"<div><p>Natural products (NPs) and their analogues have long underpinned therapies in humans, animals, and plants health, yet, discovering truly novel scaffolds remains a formidable challenge, even with the enormous diversity offered. Over the last two decades, breakthroughs in bioinformatics, cheminformatics, advanced analytical methods, synthetic biology toolkits, and optimized microbial culture have surmounted many of the bottlenecks that stalled NP research in the 1990s and 2000s. Researchers now deploy innovative extraction and purification protocols alongside high-throughput dereplication tools to fish trace metabolites out of complex matrices. These combined approaches not only enable the discovery and rigorous characterization of biosynthesized metabolites, bio-transformed analogues and new chemical entities but also allow precise tuning of biosynthetic gene clusters (BGCs) and culture conditions- modulation and optimization, dramatically improving yield, scalability, and cost-efficiency. Several of these newly unearthed compounds exhibit unique bioactivities that directly inspire drug-development programs against metabolic disorders, cancer drug resistance, and infectious diseases. In this review, we present an up-to-date, concise roadmap of natural product discovery (NPD), majorly covering strategies for awakening silent BGCs, genome mining, and late-stage diversification systems, and we discuss the current limitations and perspectives of rational NPD.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00556-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}