Natural Products and Bioprospecting最新文献

{"title":"Natural triterpenoid Ardisiacrispin B attenuates colitis-associated cancer via JAK2/STAT3 pathway and gut microbiota modulation","authors":"Hidayat Ullah,&nbsp;Huanli Cui,&nbsp;Yu Li,&nbsp;Binghuang Ye,&nbsp;Weijie Peng,&nbsp;Yongdui Ruan,&nbsp;Weibo Dai,&nbsp;Chunling Ma,&nbsp;Xianjing Hu","doi":"10.1007/s13659-026-00602-6","DOIUrl":"10.1007/s13659-026-00602-6","url":null,"abstract":"<div><p>Colitis-associated cancer (CAC) arises from persistent intestinal inflammation, immune dysregulation, and microbiota-driven epithelial injury, representing a major link between inflammatory bowel disease and colorectal malignancy. Despite advances in therapy, colon cancer remains one of the leading causes of cancer-related mortality worldwide, underscoring the urgent need for effective preventive and immunomodulatory interventions. Ardisiacrispin B (AB), a bioactive triterpenoid isolated from the <i>Ardisia</i> genus, has been reported to suppress tumor growth by regulating apoptosis and ferroptosis; however, its role in inflammation-driven colorectal tumorigenesis remains unexplored. In this study, we investigated the protective and antitumor effects of AB in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CAC mouse model, with a focus on inflammatory signaling pathways, epithelial remodeling, and gut microbiota modulation. AB administration markedly alleviated disease severity, as evidenced by a significant reduction in disease activity index, including body weight loss, diarrhea, and rectal bleeding. Histopathological evaluation revealed preserved colonic mucosal architecture, diminished inflammatory cell infiltration, and a pronounced reduction in tumor number and size. AB treatment partially modulated the gut microbiota, with a trend toward enrichment of beneficial taxa and a reduction in inflammation-associated bacterial populations. Concurrently, AB robustly downregulated the colonic expression of pro-inflammatory cytokines and chemokines. AB treatment was associated with increased expression of pro-apoptotic markers, indicative of enhanced apoptotic signaling in colonic epithelial cells, as indicated by increased expression of cleaved PARP, cleaved caspase-3, p53, and BAX, while markedly inhibiting cellular proliferation through suppression of Ki-67. Mechanistically, AB was associated with attenuation of key inflammatory and oncogenic signaling pathways, including IL-6/JAK2/STAT3, LPS/TLR4/MyD88/NF-κB, and MAPK cascades. Collectively, Ardisiacrispin B attenuates colitis-associated cancer by rebalancing gut microbiota, suppressing inflammation, and inducing tumor cell apoptosis through inhibition of key oncogenic signaling pathways.</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":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00602-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430039","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":"A critical review on the roles of natural products in shaping oral microbiota and preventing chronic diseases","authors":"Yogesh Kumar,&nbsp;Baojun Xu","doi":"10.1007/s13659-026-00605-3","DOIUrl":"10.1007/s13659-026-00605-3","url":null,"abstract":"<div><p>The oral microbiome plays a central role in maintaining both oral and systemic health, and disruptions in its balance can contribute to a wide range of diseases. This review brings together current evidence on how natural products modulate oral microbial communities, promote microbial equilibrium, and help prevent conditions such as dental caries, periodontitis, and chronic systemic disorders linked to oral dysbiosis. Recent studies highlight that phytochemicals particularly polyphenols, terpenoids, saponins, and alkaloids exert antimicrobial, anti-inflammatory, and antioxidant effects that influence bacterial adhesion, biofilm development, gene expression, and acid production. These compounds not only inhibit key oral pathogens but also support beneficial species, helping to sustain a stable and resilient microbiome. Evidence was gathered from PubMed, Scopus, ScienceDirect, and Google Scholar using relevant keywords and focusing on literature from 2015 to 2025. Insights into microbial diversity, environmental influences, host genetics, and advanced sequencing tools further strengthen understanding of oral microbial dynamics. While natural products show strong potential, challenges related to safety, bioavailability, regulatory clarity, and clinical translation remain to explore. This review outlines current progress and future directions needed to transform natural compounds into effective, evidence-based strategies for improving oral and systemic health through microbiome modulation.</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":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00605-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147337013","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":"Phenazinoates A‒E, five pairs of phenazine conjugates from a mangrove soil-derived Streptomyces strain OUCMDZ-4923","authors":"Dongyang Wang,&nbsp;Peipei Liu,&nbsp;Yukang Gao,&nbsp;Linmeng Chen,&nbsp;Liping Wang,&nbsp;Ning Li,&nbsp;Weiming Zhu","doi":"10.1007/s13659-026-00597-0","DOIUrl":"10.1007/s13659-026-00597-0","url":null,"abstract":"<div><p>Phenazinoates A–E (<b>1</b>–<b>5</b>), comprising five pairs of methyl saphenate conjugates with genistein, <i>o</i>-aminophenol, <i>p</i>-acetaminophenol and glycerol, were isolated from the fermentation broth of mangrove soil-derived <i>Streptomyces</i> sp. OUCMDZ-4923. Their structures were determined through comprehensive one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, coupled with high-resolution electrospray ionization mass spectrometry. The absolute configurations of each isomer were established by comparing experimental electronic circular dichroism spectra with calculated counterparts. Based on the biosynthetic pathway analysis, compounds <b>1</b>‒<b>3</b> were semi-synthesized from the reactions of methyl (<i>R</i>)-saphenate with genistein, <i>o</i>-aminophenol, and <i>o</i>-formamidophenol, utilizing microwave-assisted solid acid catalysis. The compounds were resolved as enantiomerically pure forms and subsequently tested for antibacterial efficacy against six pathogenic bacteria. Phenazinoates A (<b>1</b>) and B (<b>2</b>) demonstrated bioactivity against four Gram-positive bacterial strains, with minimum inhibitory concentration values ranging from 0.78 to 3.13 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":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00597-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147337065","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":"Calabanones A‒H, chromanone derivatives from the stem bark of Calophyllum calaba and their cytotoxic activities against cancer cells","authors":"Sutin Kaennakam,&nbsp;Fadjar Mulya,&nbsp;Manussada Ratanasak,&nbsp;Kitiya Rassamee,&nbsp;Pongpun Siripong,&nbsp;Yasuteru Shigeta,&nbsp;Preecha Phuwapraisirisan,&nbsp;Edwin R. Sukandar","doi":"10.1007/s13659-026-00603-5","DOIUrl":"10.1007/s13659-026-00603-5","url":null,"abstract":"<div><p>The genus <i>Calophyllum</i> (Calophyllaceae), distributed mainly in tropical regions, is rich in chromanone derivatives with diverse molecular structures that exhibit potential antimicrobial and anticancer effects. Phytochemical investigation of the stem bark of <i>C. calaba</i> collected in Thailand led to the discovery of eight previously undescribed chromanones, calabanones A–H (<b>1</b>‒<b>8</b>), and two known analogs, (‒)-isocalomembranone P (<b>9</b>) and (‒)-calomembranone P (<b>10</b>). The chemical structures of undescribed compounds were elucidated using spectroscopic analyses, particularly NMR and HRESIMS, while their absolute configurations were determined through ECD and NMR calculations combined with DP4+ probability analysis. Compounds <b>7</b> and <b>8</b> were identified as chromanone–steroid hybrids linked via an ester bond, representing the first report of such structures in plants. Cytotoxic evaluation of the isolated specialized metabolites revealed that compounds <b>6</b> and <b>9</b> displayed moderate activity against KB and HeLa S3 cancer cell lines, with IC₅₀ values ranging from 12.71 to 25.50 μM, while compounds <b>3</b>‒<b>5</b> selectively inhibited the growth of KB cells, with IC₅₀ values in the range of 18.77‒27.06 μM.</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":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00603-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147337069","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":"Three naphthomycin type polyketide compounds isolated from strain Streptomyces sp. HKIB0008","authors":"Yuan Chen,&nbsp;Fei Zhang,&nbsp;Zi-Kang Zhao,&nbsp;Lin-Fang Tang,&nbsp;Yu-Xin Sun,&nbsp;Mi-Mi Tian,&nbsp;Xing-Tao Li,&nbsp;Qian Zhao,&nbsp;Xiao-Jiang Hao,&nbsp;Mingming Cao,&nbsp;Duozhi Chen","doi":"10.1007/s13659-026-00591-6","DOIUrl":"10.1007/s13659-026-00591-6","url":null,"abstract":"<div><p>Three new naphthomycin derivatives were isolated and identified from <i>Streptomyces</i> sp<i>.</i> HKIB0008, and were designated as naphthomycin R (<b>1</b>), naphthomycin S (<b>2</b>), and naphthomycin T (<b>3</b>). Their structures were elucidated using a combination of spectroscopic techniques, including high-resolution mass spectrometry, and NMR. The naphthoquinone core of <b>1</b> underwent carbon–carbon bond cleavage, resulting in a novel structural feature, and a corresponding Baeyer–Villiger oxidation mechanism was proposed. Compounds <b>2</b> and <b>3</b> possess a complex side chain when compared to known cystine modification on the naphthalenoid core as in the case of naphthomycins I and J. In addition, the minimum inhibitory concentration (MIC) assays for these compounds were conducted.</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":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00591-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147336324","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":"Peniexpansones A–F: polyketides from Penicillium expansum DWS880 capable of enhancing the activity of fluconazole against Candida albicans","authors":"Wen-Yu Lu,&nbsp;Qing-Hui Xiao,&nbsp;Ai-Lin Liang,&nbsp;Peng-Ju Xu,&nbsp;Jing Li,&nbsp;Wen-Xuan Wang","doi":"10.1007/s13659-026-00592-5","DOIUrl":"10.1007/s13659-026-00592-5","url":null,"abstract":"<div><p>Six new polyketides, peniexpansones A–F (<b>1</b>–<b>4</b>,<b> 6</b>,<b> 7</b>), along with an additional novel compound, (2<i>E</i>,4<i>E</i>,6<i>E</i>)-8-methyldeca-2,4,6-trienoic acid (<b>5</b>), and a known naphthopyrone, were isolated from the ethyl acetate extract of rice fermented with the soil fungus <i>Penicillium expansum</i> DWS880. Structurally, peniexpansones A–D feature a highly oxygenated tetrahydronaphthalene moiety linked to an acyl chain. The structures of the new compounds were elucidated by extensive spectroscopic analysis (1D/2D NMR and HRESIMS) and further supported by quantum chemical calculations. Peniexpansone C showed weak cytotoxicity against HCT116 cells (IC₅₀ 22.81 ± 0.42 μM) and moderate antimicrobial activity against pathogens including <i>Staphylococcus aureus</i> and <i>Candida albicans</i>. Moreover, peniexpansones A and B, can significantly improve the anti-fungal activity of fluconazole against resistant <i>Candida albicans</i>. Our results provided new structures for the future development of efficiency enhancement agents for anti-fungal drugs.</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":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00592-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147336863","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":"Colloidal lignin particles for Pickering emulsion stabilization: multifunctional properties and prospects for cosmetic applications","authors":"Giovana Colucci,&nbsp;Alírio Egídio Rodrigues,&nbsp;Maria Filomena Barreiro","doi":"10.1007/s13659-026-00594-3","DOIUrl":"10.1007/s13659-026-00594-3","url":null,"abstract":"<div><p>Lignin, the most abundant aromatic biopolymer on Earth, is abundantly found as a by-product of biomass processing industries. Lignin presents remarkable properties, including antioxidant, UV-blocking, thermal stability, and antimicrobial; thus being considered a valuable feedstock to replace synthetic and fossil-based resources. Colloidal lignin particles (CLPs) are a promising strategy to overcome technical barriers in lignin valorization and have attracted increasing interest to be applied as multifunctional ingredients into several fields, including agriculture, biomedical, construction, and more recently, cosmetics. For this latter, CLPs stand out as promising Pickering stabilizers, creating opportunities for the development of surfactant-free cosmetic formulations. This review provides a current state of lignin research, focusing on the production of CLPs and Pickering emulsions and the key factors influencing their formation and stability. Recent progress in CLPs-stabilized Pickering emulsions is thoroughly addressed. Furthermore, it highlights advances on the multifunctional attributes of CLPs, including antioxidant activity, UV shielding, and demonstrated safety for cosmetic applications. The review concludes by discussing current challenges and future research directions for advancing the use of CLPs as sustainable materials in cosmetic science.</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":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00594-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147336860","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":"Nature meets machine: the AI renaissance in natural product drug discovery","authors":"Rajesh Muthuraj,&nbsp;Jaikanth Chandrasekaran","doi":"10.1007/s13659-025-00589-6","DOIUrl":"10.1007/s13659-025-00589-6","url":null,"abstract":"<div><p>Natural products (NPs) have long served as a cornerstone of drug discovery, yielding landmark therapeutics such as paclitaxel and artemisinin and providing sustained access to biologically relevant chemical space. Despite this legacy, NP-based discovery has gradually declined with the rise of synthetic chemistry and high-throughput screening, even as many contemporary “synthetic” drugs remain structurally inspired by natural scaffolds. Classical NP workflows—centered on phenotypic screening and bioassay-guided fractionation—continue to face persistent bottlenecks, including structural complexity, low bioactive yield, frequent rediscovery, and limited scalability. Rather than competing with NP research, artificial intelligence (AI) offers a complementary methodological framework to address these longstanding challenges. This review critically examines the bottlenecks inherent to traditional NP discovery and outlines how AI can be systematically integrated across the pipeline. We discuss AI-enabled advances ranging from natural language processing for mining ethnopharmacological knowledge to machine learning–driven dereplication, cheminformatics, and genome mining, with platforms such as GNPS2 exemplifying scalable progress. Case studies in antibiotic and anticancer discovery, as well as the modernization of traditional medicine, illustrate how AI–NP integration can accelerate early-stage discovery while enhancing translational relevance. Looking ahead, we examine emerging paradigms—including quantum machine learning, federated data ecosystems, and AI-assisted molecular design—that may further expand the scope of NP-based research. Collectively, this review presents a forward-looking framework in which AI functions not as a replacement for NP science, but as a synergistic discipline that enables more efficient, scalable, and informed exploration of nature-derived chemical diversity.</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":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00589-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324371","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":"Nematode-trapping fungus Arthrobotrys oligospora is hungry for iron-chelating agent COQ7 of nematodes","authors":"Qunfu Wu,&nbsp;Jiao Zhou,&nbsp;Donglou Wang,&nbsp;Songhan Xue,&nbsp;Ling Li,&nbsp;Li Wu,&nbsp;Junxian Yan,&nbsp;Xuemei Niu","doi":"10.1007/s13659-026-00590-7","DOIUrl":"10.1007/s13659-026-00590-7","url":null,"abstract":"<div><p>Iron homeostasis is critical for the survival of almost all organisms, yet its dysregulation is often caused by a synergistic effect of genetic and environmental factors. Previous studies have shown that trapping devices of the predominant nematode-trapping fungus (NTF) <i>Arthrobotrys oligospora</i> serve as an unprecedented iron sequestration system compensatory for lack of the crucial fungal vacuolar iron detoxification mechanism. Here, we found that among the Ascomycota phylum, only NTFs lacked gene <i>coq7</i>, which encodes COQ7 responsible for ubiquinol (UQ) biosynthesis and efficient iron chelation. Addition of exogenous UQ₁₀ or heterologous expression of yeast gene <i>coq7</i> in <i>A. oligospora</i> inhibited the formation of fungal trapping devices<i>.</i> Interestingly, mutant nematodes with disruption of gene <i>coq7</i> can greatly reduce nematode-capturing ability of fungal trapping devices. Exogenous COQ7s exhibit significant adsorption effects on fungal trapping devices both in vitro and in vivo. Transcriptional, metabolic, mutational, and phenotypic analyses indicated that <i>A. oligospora</i> utilized a chemotaxonomic class of highly oxygenated arthrobotrisins with similar characteristics to UQ₃, instead of UQs, in response to elevated oxygen levels. Loss of arthrobotrisin biosynthesis led to a delayed growth of the mutant Δ<i>art</i> but enhanced UQ₈ biosynthesis, trapping device formation, and nematicidal activity. Time-calibrated evolutionary analyses, combined with geological data, indicated that the NTF ancestor lost the <i>coq7</i> gene after acquiring the <i>art</i> gene cluster during the cold “superoligotrophy” period, characterized by dramatic shifts in global oxygen levels and temperature changes. Our findings indicated that the trapping devices of NTF capture nematodes primarily for iron chelation therapy, rather than solely for food, which addresses the long-standing issue regarding the limited carnivorous ability of trapping devices.</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":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00590-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324321","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":"De novo synthesis of plant polyketide plumbagin in yeast: a platform for sustainable production of naphthoquinones","authors":"Arati P. Vasav,&nbsp;Vitthal T. Barvkar","doi":"10.1007/s13659-025-00588-7","DOIUrl":"10.1007/s13659-025-00588-7","url":null,"abstract":"<div><p>Plumbagin is a natural naphthoquinone with different pharmacological properties and abundantly present in the roots of <i>Plumbago zeylanica</i> L. In spite of its therapeutic anti-cancerous potential, its limited availability from plant sources has slowed down its large scale production. In the present study, we report the heterologous reconstruction of the complete plumbagin biosynthetic pathway in <i>Saccharomyces cerevisiae</i> using six functionally characterized genes from <i>P. zeylanica</i> viz. <i>Polyketide synthase</i> (<i>PKS</i>), <i>Polyketide cyclase</i>, <i>Aldo–keto reductase</i> (<i>AKR1</i>), two <i>cytochrome P450 monooxygenases</i> (<i>CYP81B140</i> and <i>CYP81B141</i>), and a <i>cytochrome P450 reductase</i> (<i>CPR</i>). Stepwise pathway engineering was performed to evaluate the necessity and sufficiency of individual and combined gene sets. The expression of PKS alone was not able to synthesize measurable products, while the co-expression of <i>PKS</i>, <i>cyclase</i>, and <i>AKR1</i> (PCA) enabled the biosynthesis of 3-methyl-1,8-naphthalenediol which is a key intermediate and also confirmed by LC–MS/MS. The addition of <i>CYP81B140</i> and <i>CPR</i> (PCACC) led to the production of 3-methyl-1,8-naphthalenediol and isoshinanolone, and further addition of <i>CYP81B141</i> (PCACCC) in yeast effectively biosynthesized plumbagin. These results confirm the functional roles of all six genes and demonstrate full pathway reconstruction in yeast from the primary precursors acetyl-CoA and malonyl-CoA. The present study establishes a microbial production platform for plumbagin and provides valuable insights into the biosynthesis of plant-derived naphthoquinones as well as paving the way for the sustainable and scalable production of medicinally important compounds.</p></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00588-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324288","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}