Natural Product Reports最新文献

{"title":"Construction of C(sp³)-C(sp³) attached ring motifs in natural product synthesis.","authors":"Søren L B Møller, Thomas B Poulsen","doi":"10.1039/d6np00024j","DOIUrl":"10.1039/d6np00024j","url":null,"abstract":"<p><p>Covering the literature until 2025C(sp³)-C(sp³) attached ring systems represent some of the most structurally intriguing and synthetically challenging polycyclic motifs found in natural products. Methods for their concise construction remain underdeveloped due to steric congestion and limited stereocontrol arising from the absence of inherent topological bias at fully saturated bridgehead carbons. In this review, we survey the different strategies and mechanistic frameworks that have been applied to assemble C(sp³)-C(sp³) attached rings. We first highlight selected examples of indirect approaches-including tethering and rearrangements-which continue to offer powerful solutions when direct coupling reactions are infeasible. We then place particular emphasis on fragment couplings, as well as derived cascade processes, that enable direct formation of saturated attached ring motifs, since such transformations can provide highly convergent access to complex target structures. Against the backdrop of natural product examples that illustrate both current successes and remaining limitations, we conclude by discussing emerging methods that may drive future advances toward making predictive, stereocontrolled construction of saturated attached rings a routine element of complex molecule synthesis and medicinal chemistry design.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":"1265-1284"},"PeriodicalIF":12.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From gene discovery to synthetic biology: recent advances in the biosynthesis of oleanane-type pentacyclic triterpenoids.","authors":"Ismail Abdelsamad, Mohamed Abdulbagi, Jingya Wang, Zheyong Xue, Xu Lu","doi":"10.1039/d6np00013d","DOIUrl":"10.1039/d6np00013d","url":null,"abstract":"<p><p>Covering: 2010 to January 2026Oleanane-type pentacyclic triterpenoids (OPTs) represent a prominent class of plant-derived natural products, widely recognized for their potent pharmacological properties, including anticancer, anti-inflammatory, and antidiabetic effects. Although they have significant therapeutic potential, their production is limited by their low natural abundance, intricate biosynthetic pathways, and complex regulatory mechanisms. Recent advances have substantially improved our understanding of the biosynthesis of OPTs, particularly focusing on the elucidation of key enzymes, such as β-amyrin synthases (β-ASs), cytochrome P450 monooxygenases (CYP450s), and UDP-glycosyltransferases (UGTs). Sophisticated transcriptional regulation of OPT biosynthesis is achieved through diverse transcription factors (TFs), which integrate signals from hormonal elicitors, environmental stimuli, and metabolic feedback. Additionally, microRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators, adding another dimension to the complex regulatory networks influencing OPT production. Modern approaches integrating genomics, transcriptomics, proteomics, metabolomics, and advanced computational tools have facilitated the discovery and functional characterization of novel genes and pathways, enabling targeted metabolic engineering strategies. Moreover, recent developments in synthetic biology, including heterologous expression platforms in microbial and plant hosts and innovative genome-editing techniques, offer powerful tools to overcome the current production bottlenecks of OPTs. The integration of artificial intelligence (AI) and machine learning (ML) into OPT research promises a paradigm shift from empirical trial-and-error methods to predictive optimization, facilitating the systematic discovery of biosynthetic gene clusters, rational engineering of key enzymes, and pathway optimization to unlock sustainable and high-yield production of OPTs. This review summarizes the recent advancements in biosynthetic gene discovery, regulatory mechanisms, and synthetic biology strategies for enhancing the OPT production, highlighting future opportunities for the sustainable and scalable production of these valuable natural compounds.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":"1462-1481"},"PeriodicalIF":12.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in decoding biosynthetic pathways and synthetic biology approaches for plant alkaloids.","authors":"Lanyu Zhou, Haiyue Gong, Huan Zhao, Luqi Huang, Yating Hu","doi":"10.1039/d5np00089k","DOIUrl":"10.1039/d5np00089k","url":null,"abstract":"<p><p>Covering: 2018 to 2025Alkaloids represent a large and structurally diverse class of natural products predominantly found in plants and rarely in animals. Well-known compounds such as vinblastine, berberine, and scopolamine exhibit remarkable pharmaceutical potential, with several already in clinical use. These plant-derived alkaloids have attracted enduring interest due to their diversity, structural complexity, and pronounced biological activities, making them a privileged resource for drug discovery. In recent years, breakthrough advances have been made in elucidating the biosynthetic pathways of plant alkaloids, making this a highly promising research field. Successful cases including reserpine, strychnine, and hyoscyamine have not only provided novel strategies for drug development and sustainable production, but also greatly stimulated scientific enthusiasm. In this review, we focus on representative plant alkaloids from major classes including monoterpene indole alkaloids (MIAs), tetrahydroisoquinoline alkaloids (THIQAs), tropane alkaloids (TAs), and other types, covering the period from 2018 to 2025. It highlights key challenges in pathway elucidation, including stereochemical control (<i>R</i>/<i>S</i> configuration), important cyclization, and tailoring modifications particularly those catalyzed by specific enzymes. This review also covers catalytic sequence determination, and innovative approaches for long-pathway decoding. Furthermore, we discuss how synthetic biology and metabolic engineering strategies enable efficient and sustainable microbial production of these compounds. By identifying common obstacles and proposing effective solutions, this review aims to inspire researchers engaged in functional gene characterization, synthetic biosystems development, yield optimization, and drug innovation for plant alkaloids. It seeks to promote interdisciplinary collaboration across botany, chemistry, biology, and pharmaceutical sciences, thereby accelerating the discovery and scalable production of high-value plant alkaloids.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":"1440-1461"},"PeriodicalIF":12.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The isolation, biosynthesis, biological profiles and synthesis of the pterocarpans, pterocarpenes and coumestans: isoflavone derivatives with pharmacological utility.","authors":"Liangguang Jack Yi, Lorenzo V White, Martin G Banwell","doi":"10.1039/d6np00007j","DOIUrl":"10.1039/d6np00007j","url":null,"abstract":"<p><p>Covering the literature up to December 2025The pterocarpans, pterocarpenes and coumestans are closely related, plant-derived secondary metabolites that display a diverse range of biological effects. As such they are attracting increasing attention as potential leads in the development of new therapeutic agents and as targets for chemical synthesis. This review, which covers all three structural classes in an integrated way, outlines some of the more recent and pertinent developments in this particularly active area of natural products research.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":"1285-1307"},"PeriodicalIF":12.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fungal polyketide biosynthesis as a platform for designer natural products.","authors":"Pingxin Lin, Zhenhao Fu, Ye Li, Yeo Joon Yoon, Sang Yup Lee","doi":"10.1039/d5np00092k","DOIUrl":"10.1039/d5np00092k","url":null,"abstract":"<p><p>Covering: 2010 to 2025Polyketides constitute a vast family of structurally and functionally diverse natural products that underpin numerous pharmaceuticals, nutraceuticals, and materials. Among them, fungal typve I iterative polyketide synthases (iPKSs) orchestrate highly programmable catalytic cycles that transform simple acyl-CoA precursors into architecturally complex molecules. Understanding the programming logic of these multidomain enzymes has revealed how chain-extension, reduction, and cyclization patterns are encoded, offering a foundation for rational pathway engineering. Recent advances in structural biology, cryo-electron microscopy (cryo-EM) analysis, and computational modelling have clarified the conformational dynamics of iPKSs and their collaborating enzymes, while combinatorial biosynthetic strategies now enable the creation of non-natural scaffolds and expanded chemical diversity. Parallel progress in fungal and yeast cell-factory engineering-spanning metabolic rewiring, organelle compartmentalization, and dynamic control-has substantially improved the efficiency and scalability of polyketide production. This review integrates mechanistic insights with biotechnological innovation, highlighting emerging rules for programmable PKS design and discussing future directions toward AI-assisted, high-throughput platforms for sustainable industrial biosynthesis of fungal polyketides.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":"1219-1264"},"PeriodicalIF":12.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeleton innovation <i>versus</i> structural diversification in terpenoid discovery: chemoinformatic insights from TeroKit.","authors":"Tao Zeng, Jiahao Li, Ruibo Wu","doi":"10.1039/d6np00004e","DOIUrl":"10.1039/d6np00004e","url":null,"abstract":"<p><p>Covering: up to the end of 2025Terpenoids, as one of the largest classes of natural products, derive their vast structural diversity from a combination of complex cyclic skeletons and extensive post-modifications. Although new terpenoids continue to be discovered, it has remained unclear whether contemporary research is primarily in a phase of exploring novel carbon skeletons or exploiting known ones through elaboration. Our systematic chemoinformatic investigation reveals that terpenoid discovery in the past six years has been overwhelmingly dominated by the exploitation of known skeletons through diverse modifications. This trend is largely driven by the current, activity-guided discovery paradigm, which prioritizes compounds with drug-like properties and immediately assayable bioactivity, thereby focusing effort on the elaboration of accessible chemical space. This quantitative profiling provides a clear framework for understanding the present trajectory of the field and underscores the need to strategically rebalance exploration and exploitation in future research, guiding efforts toward uncovering truly unprecedented and biologically relevant terpenoid architectures.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":"1209-1218"},"PeriodicalIF":12.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAM is not the SAM(e): diastereomers of an important cofactor.","authors":"Agnes Bartels, Philipp Germer, Jennifer N Andexer","doi":"10.1039/d6np00059b","DOIUrl":"https://doi.org/10.1039/d6np00059b","url":null,"abstract":"<p><p>The cofactor <i>S</i>-adenosylmethionine (SAM, AdoMet) is generally considered to be only its canonical (<i>S</i>_S,<i>S</i>_{C_α})-SAM diastereomer. In this viewpoint, we highlight that exceptions are present in some salvage pathways and many SAM-utilising enzymes tolerate alternative configurations at the two stereogenic centres of the methionine-derived moiety. This reveals stereochemical flexibility with important implications for enzyme function and natural product biosyntheses.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terpene synthases are highly substrate tolerant - among them BcBOT2 is a \"jack of all trades\".","authors":"Jan Luca Budde, Mehdi D Davari, Ahmed Hassanin, Mikail Karacam, Andreas Kirschning, Henry Struwe, Daghan Taser","doi":"10.1039/d6np00040a","DOIUrl":"https://doi.org/10.1039/d6np00040a","url":null,"abstract":"<p><p>Covering: up to 2026A traditional view regarding enzymes assigns them a markedly low substrate promiscuity. This is based, among other factors, on concepts concerning the evolution of metabolism, which, according to the \"patchwork model\", assumes that the first enzymes converted a variety of substrates more or less effectively into quite different products and that enzymes then differentiated through evolution and became more substrate selective. Starting from linear oligoprenyl diphosphate precursors, terpene synthases produce oligocyclic terpenes <i>via</i> complex carbocation cascades. It was found that these sometimes exhibit unusual substrate acceptance. Using the example of the fungal sesquiterpene synthase BcBOT2, it is shown that the \"terpenome\" can be expanded in an unprecedented way, whereby completely new terpene backbones can be generated that nature is usually unable to access, as of today.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The golden decade of eburnamine-vincamine alkaloid synthesis: 2015 to present.","authors":"Huijing Wang, Jiayi Mu, Yangyang Zhong, Pei Tang, Fener Chen","doi":"10.1039/d6np00054a","DOIUrl":"https://doi.org/10.1039/d6np00054a","url":null,"abstract":"<p><p>Covering: 2015 to 2026Eburnamine-vincamine alkaloids are unique monoterpenoid indole alkaloids with unprecedented structures and notable biological properties. Four eburnamine-vincamine alkaloids, namely vincamine, vinburnine, brovincamine, and vinpocetine have been approved for clinical treatment. In addition, numerous bioactive derivatives have been used in clinical trials. Since 2015, several synthetic strategies, particularly asymmetric approaches, have emerged to achieve significant progress in the total synthesis of eburnamine-vincamine alkaloids. The main synthetic challenge posed by their structures is the construction of the rigid polycyclic skeleton and installation of the C20/C21 (or C3/C14) contiguous stereocenters. These total synthesis endeavors are considered highly desirable and could fuel advances in medicinal chemistry of eburnamine-vincamine. In this review, recent reports (mainly from 2015 to 2026) on the total synthesis of eburnamine-vincamine natural products and their derivatives (eburnane-vincane, tacaman, schizozygane, and bisindole groups) are reported and discussed.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in the complexity-to-diversity strategy for natural product-like compound synthesis: two sides of the same coin.","authors":"María Luz Tibaldi Bollati, Manuela García","doi":"10.1039/d6np00019c","DOIUrl":"https://doi.org/10.1039/d6np00019c","url":null,"abstract":"<p><p>Covering: up to the end of 2025Natural products have long served as valuable therapeutic agents owing to their high structural complexity, rich stereochemistry, and three-dimensional architecture. Nevertheless, the difficulty of isolating novel natural products in substantial quantities has shifted drug-discovery efforts over the past two decades toward simpler synthetic libraries, often at the expense of biologically relevant chemical space. The complexity-to-diversity (CtD) strategy offers a compelling alternative: by distorting and reorganizing natural-product scaffolds, CtD efficiently generates structurally diverse, highly complex small molecules capable of engaging challenging biological targets. Recent advances have demonstrated the power of this approach, enabling concise, scalable syntheses of diverse libraries through strategic skeletal rearrangements. This viewpoint highlights the unique potential of CtD predominantly derived from alkaloidal and terpenoidal nuclei, examines representative synthetic examples, and discusses the opportunities and challenges inherent to scaling both structural complexity and molecular diversity. This perspective aims to underscore the relevance of CtD for natural product, synthetic, and medicinal chemists seeking new avenues for innovative lead discovery.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}