Natural Product Reports最新文献

{"title":"Ecological context for bacterial natural products discovery.","authors":"Jonathan Parra, Marla I Macias-Contreras, Dulce G Guillén Matus, Katherine R Duncan","doi":"10.1039/d6np00018e","DOIUrl":"10.1039/d6np00018e","url":null,"abstract":"<p><p>Covering: This review covers literature from 2015 to present.It is widely recognised that there is a significant gap between bacterial natural product potential and detected/described products. As such, there are several recent reviews on elicitation strategies for natural products discovery, which are often laboratory focused. Recently, a move to more ecology-focused approaches to understand the function of metabolites in nature and what impacts expression has been a growing trend. In this review, we aim to capture work done that goes beyond laboratory conditions and address ecological studies focussed on what impacts bacterial chemistry, covering both abiotic and biotic influences. We aim to touch on the impact of biodiversity loss, changes in ecosystems and future climate parameters and the implications this will have on natural products chemistry and biodiscovery efforts, the scale and consequences of which are not known.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":"1542-1562"},"PeriodicalIF":12.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256289","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":"Growth, signals, and survival: the evolutionary divergence of terpenoid metabolism in terrestrial plants.","authors":"Gabrielle Wyatt, Farida Yasmin, Aubanie R Donaldson, Siena L Schumaker, Gloria-Alexandra Gueorguieva, Philipp Zerbe","doi":"10.1039/d6np00035e","DOIUrl":"https://doi.org/10.1039/d6np00035e","url":null,"abstract":"<p><p>Covering: primarily from 2011 to 2026Terpenoids are an ancient and immensely diverse class of natural products. Since their emergence more than two billion years ago alongside early biological membranes, terpenoid metabolism has undergone a vast expansion in both structure and function, which directly contributed to the ecological success of terrestrial plants. Biosynthetically derived from two isomeric five-carbon isoprenoid precursors, plant terpenoids include hemi-, mono-, sesqui-, di-, sester-, tri-, tetra-, and poly-, and mero-terpenoids, that exhibit extensive variation in chain length, structural scaffolds, and functional decoration. This large chemical space is generated <i>via</i> dynamic metabolic networks, in which functionally versatile enzymes - most notably scaffold-forming terpene synthases and tailoring cytochrome P450 monooxygenases - are assembled into combinatorial pathway modules to yield complex bioactive terpenoid structures. Lineage-specific expansion of the underlying gene families, driven by recurrent genome and gene duplications followed by functional divergence, have facilitated the evolution of both conserved and specialized metabolic branches and natural products. Functionally, conserved terpenoids act as phytohormones, signaling molecules, and pigments governing plant growth and development, whereas typically species-specific specialized terpenoids mediate dynamic plant-environment interactions, including pest and pathogen defenses, allelopathy, pollinator attraction, root-microbiome communication, and abiotic stress tolerance. Advances in genomics, metabolomics, and synthetic biology continue to accelerate the discovery of terpenoid structures, pathways, and functions at an ever-increasing pace. Elucidating the mechanisms that generate this diversity, and the multifaceted roles that terpenoids play in plant ecology and physiology not only deepens our understanding of the evolutionary history of terrestrial plants, but also unlocks new opportunities for biotechnological innovation, spanning terpenoid-derived therapeutics, biofuels, fragrances, polymers, agrochemicals, and many other bioproducts.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757143","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":"<i>C</i>-Methylated natural products: biosynthetic stage and significance of <i>C</i>-methylation.","authors":"Fumitaka Kudo","doi":"10.1039/d6np00056h","DOIUrl":"10.1039/d6np00056h","url":null,"abstract":"<p><p>Covering: up to 2026<i>C</i>-Methylation is a fundamental transformation in natural product biosynthesis. Although methyl groups are often regarded as simple functional groups that modulate physicochemical properties, they frequently play decisive roles in directing enzymatic reactivity and controlling biosynthetic pathway progression. Cobalamin (Cbl)-dependent radical <i>S</i>-adenosyl-L-methionine (SAM) <i>C</i>-methyltransferases catalyze the installation of <i>C</i>-methyl groups at sp³-hybridized carbon centers in biosynthetic intermediates. Recent studies have uncovered their remarkable catalytic capabilities, including precise control over regio- and stereoselectivity. Moreover, the installed methyl groups often influence downstream transformations and are essential for late-stage biosynthetic events. This highlight focuses on the functional roles of <i>C</i>-methylation mediated by Cbl-dependent radical SAM enzymes, emphasizing how these seemingly small modifications shape the biosynthesis of complex natural products.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719415","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":"Pyrrocidines and hirsutellones: distinctive fungal polyketide alkaloid hybrids with intriguing therapeutic applications: a comprehensive update.","authors":"Mohamed A Tammam, Islam El-Awaad, Adnane Aouidate, Reham Hassan Mekky, Amr El-Demerdash","doi":"10.1039/d6np00044d","DOIUrl":"https://doi.org/10.1039/d6np00044d","url":null,"abstract":"<p><p>Covering: 2005-2025Pyrrocidines and hirsutellones are a fascinating class of fungal natural products that possess an intricate chemical structure characterized by a distinctive macrocyclic ring fused to a decahydrofluorene core. Known for their complex architectures as PKS-NRPS hybrids, these metabolites are isolated from various fungi and have attracted significant attention due to their potent pharmacological properties, including antimicrobial, antifungal, and anticancer effects. This review article aims to shed light on the structural diversities of 52 fungal-derived pyrrocidines and hirsutellones reported over the period of 2005-2025, providing insights into their chemistry, biosynthetic origins, pharmacokinetic profiles, and structure-activity relationships (SARs). Furthermore, we critically evaluate their promising therapeutic potential, highlighting the opportunities they present for modern drug discovery and development.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710645","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":"Construction of cell factories, and multi-enzymatic and chemoenzymatic cascades to enable the efficient production of alkaloids.","authors":"Zhenbo Yuan, Huiling Liu, Fei Li, Qingli Xiong, Shuaiju Liu, Yue Gao, Yijian Rao","doi":"10.1039/d6np00031b","DOIUrl":"https://doi.org/10.1039/d6np00031b","url":null,"abstract":"<p><p>Covering: up to 2025Alkaloids constitute an invaluable reservoir for pharmaceutical discovery. However, their therapeutic development has long been constrained by the inefficiencies of plant extraction, as well as the economic impracticality of total chemical synthesis. In recent years, biomanufacturing has emerged as a transformative paradigm, enabling sustainable and scalable access to these complex molecules. This review provides an overview of the pivotal advances in alkaloid biosynthesis, delineated across <i>de novo</i> biosynthesis in prokaryotic and eukaryotic systems, concise multi-enzyme cascades, and chemoenzymatic synthesis. By discussing these pioneering examples, analyzing the strategic lessons, inherent limitations, and corresponding solutions for these platforms, this review illuminates how synthetic biology and biocatalysis are collectively reshaping the landscape of alkaloid production and paving the way for their expanded pharmaceutical applications.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148704598","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":"Mechanistic insight into radical <i>S</i>-adenosylmethionine enzymes in lipid modification.","authors":"Tamra Blue-Lahom, Jiayuan Cui, Cody T Lloyd, Squire J Booker","doi":"10.1039/d6np00037a","DOIUrl":"10.1039/d6np00037a","url":null,"abstract":"<p><p>Covering: up to 2025Lipids are structurally diverse biomolecules that play a critical role in the homeostasis of organisms across all domains of life. While biogenesis of lipids varies by organism, the strategies employed to modify or functionalize inert lipid hydrocarbon chains often require the power of radical-based chemistry. Recently, an increasing number of lipid-modifying radical <i>S</i>-adenosylmethionine (RS) enzymes have been identified. RS enzymes are well known to mediate >100 reactions. In the context of lipids, these radical-mediated reactions proceed through Csp² and Csp³ centers, affording C-C bond formations, methylations, cyclizations, and/or ring contractions. This review highlights our understanding of the function and mechanism of lipid-modifying RS enzymes. Mechanistic considerations of lipid modification by RS enzymes reveal the significance of cofactors (particularly B12) and auxiliary metal centers in substrate activation and intermediate stabilization. Understanding the function and mechanism strategies of these enzymes is crucial not only to advancing our understanding of RS enzymes but also to inform paleoenvironmental reconstructions and the emerging field of lipid-based drug delivery.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148704643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial cytological profiling for mode-of-action discovery of natural product-derived antibiotics: progress, challenges, and future directions.","authors":"Poochit Nonejuie, Thanadon Samernate, Filosofia F T A Prasasti, Vorrapon Chaikeeratisak, Joe Pogliano","doi":"10.1039/d6np00017g","DOIUrl":"https://doi.org/10.1039/d6np00017g","url":null,"abstract":"<p><p>Covering: 2013 up to 2026The rapid escalation of antimicrobial resistance has outpaced the discovery of natural product (NP)-derived antibiotics, underscoring the need for new strategies to identify and characterize antibacterial agents. NPs have historically dominated antibiotic development due to their structural and mechanistic diversity, yet their chemical complexity, low abundance, laborious dereplication, and challenging mode of action (MoA) identification continue to limit discovery efficiency. Bacterial Cytological Profiling (BCP), an image-based phenotypic screening, has emerged as a powerful approach capable of capturing rich, single-cell-resolved responses, making it particularly well suited for investigating complex NP-derived antibiotic discovery. This review focuses on how BCP, a prokaryotic image-based strategy central to antibiotic MoA elucidation, addresses key challenges in NP-derived antibacterial discovery, including dereplication, deconvolution of multiple MoAs, and identification of novel mechanisms. We also discuss current biological and methodological limitations of the approach and provide practical perspectives for NP researchers seeking to implement BCP in discovery programs. Finally, we examine how lessons from the widely adopted eukaryotic image-based profiling method, the Cell Painting Assay, could inform future BCP development and propose a \"BCP v1.0\" framework to facilitate broader adoption and ultimately accelerate NP-derived antibiotic discovery.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682764","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 complexity cliff in natural product discovery: why full automation remains elusive and the case for collaborative intelligence.","authors":"Ran Lin, Chengzeng Zhou, Rongzhen Wu, Yinan Wang, Bin Wu, Zixin Deng, Jiangtao Gao","doi":"10.1039/d5np00086f","DOIUrl":"https://doi.org/10.1039/d5np00086f","url":null,"abstract":"<p><p>Covering: 1992 to 2025Natural products contribute to roughly half of FDA-approved small-molecule drugs, yet their discovery has remained surprisingly resistant to the automation that has reshaped synthetic medicinal chemistry. In this review, we examine why. We propose that natural product workflows encounter a \"complexity cliff\", a threshold beyond which automation success rates fall sharply rather than degrading gradually. We define the complexity cliff in operational terms as a discontinuity in the performance of standardized, scaled pipelines, which is triggered when chemical, biological or ecological complexity exceeds the assumptions encoded in the workflow. The cliff manifests across three coupled axes: a chemical axis, where unprecedented scaffolds and stereochemistry overwhelm pattern-based dereplication and structure elucidation; a biological axis, where unculturable organisms, silent biosynthetic gene clusters and context-dependent metabolite production frustrate standardized cultivation; and an operational axis, where matrix-specific extraction, scale-up and sustainable sourcing resist consistency-driven design. We distinguish challenges that are intrinsic to natural product research from those that are unique to automation, and we argue that several often-cited \"automation barriers\" (such as scale-dependent yields) are, in fact, universal pre-automation problems for which automation may help rather than hinder. Emerging technologies, including AI- and machine-learning-guided genome mining, CRISPR-enabled pathway engineering and ecosystem-scale digital twins, address parts of the cliff but not its serendipitous core. We close by arguing that the most productive path forward is not full autonomy but a collaborative intelligence framework: machine throughput and pattern recognition coupled with human curiosity, biological intuition, and willingness to follow anomalies. This framing reframes the central question from \"how do we automate natural product discovery?\" to \"how do we partition natural product discovery between humans and machines so that each side does what it does best?\"</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676176","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":"Oxygen-independent enzymatic dearomatization of homocyclic aromatic compounds.","authors":"Tingyi Zhan, Juliane Breiltgens, Lena Appel, Lina Peller, Syed Masood Husain, Michael Müller, Matthias Boll","doi":"10.1039/d6np00062b","DOIUrl":"https://doi.org/10.1039/d6np00062b","url":null,"abstract":"<p><p>Covering: 1995 up to the end of 2025Homocyclic aromatic compounds (HAC) represent the second most abundant class of natural and anthropogenic products. Their biodegradation is central to the global carbon cycle and the bioremediation of aromatic pollutants. A key step in this process is enzymatic dearomatization, historically attributed exclusively to oxygen-dependent mono- or dioxygenases. However, over the past three decades, a growing diversity of oxygen-independent dearomatizing reductases has been identified. These enzymes act either on partially activated di- or trihydroxybenzenes and trihydroxynaphthalenes with <i>meta</i>-oriented hydroxyl groups, or on coenzyme A (CoA) thioesters of carboxylated HAC, converting aromatic substrates into cyclic dienes. Class I and II benzoyl-CoA reductases catalyze Birch-like reductions <i>via</i> radical intermediates at metal cofactors, with low-potential electrons supplied either through ATP-dependent electron transfer (class I) or flavin-based electron bifurcation (class II), whereas 2-naphthoyl-CoA reductase appears independent of an electron-activation system. An alternative, non-redox dearomatization mechanism has been identified in <i>S</i>-adenosyl-L-methionine-dependent methyltransferases involved in the anaerobic bacterial estrogen-to-androgen conversion, as well as in polyketide tailoring. Together, these findings reveal a broad enzymatic repertoire for overcoming arene resonance stabilization under anoxic conditions. Beyond their ecological significance, these pathways provide mechanistically diverse routes and opportunities for biocatalysis and the sustainable synthesis of valuable chemical building blocks.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663145","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":"Volatile dialogues between plants and microorganisms.","authors":"Muhammad Syamsu Rizaludin, Jeroen S Dickschat, Jos M Raaijmakers, Paolina Garbeva","doi":"10.1039/d6np00045b","DOIUrl":"https://doi.org/10.1039/d6np00045b","url":null,"abstract":"<p><p>Covering: up to 2026Volatile organic compounds (VOCs) are key mediators of long-distance communication in biological systems. While their roles in plant-insect interactions are well established, emerging evidence highlights their importance in plant-microbe interactions. In this highlight, we discuss the biosynthesis and ecological functions of plant VOCs (pVOCs) and their impact on microbiome assembly and function. We examine how constitutive and stress-induced pVOCs shape microbial community composition and how microbial VOCs (mVOCs) influence plant growth and defense by modulating hormonal and metabolic pathways. We further address the bidirectional nature of volatile-mediated interactions and the challenges associated with studying complex VOC blends in natural environments. Understanding these dynamic volatile dialogues provides new opportunities for microbiome engineering and sustainable crop production.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663160","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}