Natural Product Reports最新文献

{"title":"Natural products in antiparasitic drug discovery: advances, opportunities and challenges","authors":"Xiaofei Shang ,&nbsp;Lixia Dai ,&nbsp;Xinyuan Cao ,&nbsp;Yudong Ma ,&nbsp;Ilgekbayeva Gulnaz ,&nbsp;Xiaolou Miao ,&nbsp;Xiuhui Li ,&nbsp;Xiaorong Yang","doi":"10.1039/d5np00007f","DOIUrl":"10.1039/d5np00007f","url":null,"abstract":"<div><div>Covering: up to 2024.</div></div><div><div>Parasites infect hundreds of millions of people, result in significant disability rates and mortality and lead to devastating social and economic consequences, especially in developing countries and regions. Traditional medicines have been used for centuries to treat parasitic diseases. Some natural products (NPs) and their derivatives have been derived from these medicines and applied in clinical settings, attracting the attention of the scientific community throughout history. With the development and application of revolutionized technologies over the past few years, more promising compounds have been found from natural resources and provided new possibilities for the development of novel antiparasitic drugs. In this review, we aimed to discuss the strategies used for developing drugs from natural resources and mainly describe the causative pathogens, epidemiology and current treatment of parasitic diseases. Promising NPs and their derivatives are listed, and their effectiveness, potential mechanism and structural optimization are described. Subsequently, the advantages and limitations of the drug development process and the role of technologies in this process are discussed. A prospective analysis of research on and development of antiparasitic drugs based on NPs is presented. The high attrition rates, accessibility, sustainable supply, IP constraints and other problems still hinder the development of NPs; however, the therapeutic significance and broad clinical utilization of approved natural product-derived drugs, exemplified by quinine, artemisinin, and ivermectin in treating parasitic diseases, underscore that natural products remain a highly promising reservoir of chemical agents. Their exceptional structural diversity and marked bioactivities continue to stimulate scientific interest in novel antiparasitic drug discovery. In combination with the recent development and application of revolutionized technologies, NPs will provide a stronger basis for drug discovery and will continue to provide major contributions to human and veterinary health.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 9","pages":"Pages 1419-1458"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273677","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 ballet of nature: the interconvertible isomerisation of natural products","authors":"Ze-Jun Xu ,&nbsp;Jing-Jing Han ,&nbsp;Chun-Yang Zhang ,&nbsp;Hong-Xiang Lou","doi":"10.1039/d5np00019j","DOIUrl":"10.1039/d5np00019j","url":null,"abstract":"<div><div>Covering: up to 2025</div></div><div><div>The diverse interconversion of isomers among natural products (NPs) are shaped by both intrinsic structural characteristics and extrinsic environmental factors, representing a rich source of chemical complexity and biological diversity. Deciphering these intricate interconversion processes holds the potential to unlock a vast array of bioactive compounds, expanding our exploration of the chemical landscape. Identifying the specific conditions and molecular characteristics while accurately predicting ‘the ballet of nature’ will effectively achieve increased activity, lower toxicity, and superior pharmacokinetics. Such advancements will significantly broaden their applications in the development of valuable pharmaceuticals and products for medicine, agriculture, and industry. This review comprehensively outlines the origins and chemical classifications of paired interconvertible isomers in nature, including positional, tautomeric, geometric, optical, and conformational isomerism. Particular focus is given to the formation mechanisms of these interconversion processes.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 9","pages":"Pages 1548-1574"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473390","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":"Progress on targeted discovery of microbial natural products based on the predictions of both structure and activity.","authors":"Yuwei Zhang, Jianfa Zong, Yufeng Liu, Keyu Zhou, Haibo Shi, Wen-Bing Yin, Ling Liu, Yihua Chen","doi":"10.1039/d5np00008d","DOIUrl":"https://doi.org/10.1039/d5np00008d","url":null,"abstract":"<p><p>Covering: up to 2025Microbial natural products (NPs) with diverse structures and fascinating activities are a fertile source of drug discovery. Genomic and metagenomic data have revealed that there are abundant valuable resources to be explored. With the advancement in technology, methods for discovering NPs from microorganisms are undergoing notable changes. In this highlight article, we summarized different NP discovery methods into activity-guided and structure-guided categories, emphasizing the characteristics of target compounds and providing typical examples of NPs. We primarily focused on recently developed representative methods that can simultaneously predict the structure and activity features of target compounds as well as the discovery trends of NPs reflected by these cutting-edge methods.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582632","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":"Prenylated bacterial natural products: occurrence, chemical diversity, biosynthesis and bioactivity","authors":"Fan Zhang ,&nbsp;Di Zhao ,&nbsp;Yuzhu Wu ,&nbsp;Lei Li","doi":"10.1039/d5np00011d","DOIUrl":"10.1039/d5np00011d","url":null,"abstract":"<div><div>Covering: 2000 to 2024</div></div><div><div>Prenylated bacterial natural products (NPs), catalyzed by cluster-situated prenyltransferases (PTs), exhibit large structural diversity and broad biological activities and have received increasing attention for novel drug discovery and development. This review provides a comprehensive summary of the recent progress in the investigation of prenylated bacterial NPs. To highlight the structural and chemical space of prenylated bacterial NPs, we discuss their occurrence, structures, biosynthesis and bioactivities. Representative examples are summarized with illustrations of PT-catalyzed biosynthetic pathways of distinct NP classes, which present new opportunities for the discovery of novel prenylated bacterial NPs. The mechanistic study of PTs involved in bacterial NP biosynthesis has been outlined, and prenylated bacterial NPs hold great promise as novel biocatalysts for the synthesis of novel drug leads in modern medicine.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 8","pages":"Pages 1303-1343"},"PeriodicalIF":10.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075112","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":"Hot off the Press","authors":"Robert A. Hill ,&nbsp;Andrew Sutherland","doi":"10.1039/d5np90029h","DOIUrl":"10.1039/d5np90029h","url":null,"abstract":"<div><div>A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as hypbeaone A from <em>Hypericum beanii</em>.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 8","pages":"Pages 1235-1239"},"PeriodicalIF":10.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751900","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":"Remodeling of ribosomally synthesized peptide backbones based on posttranslational modifications","authors":"Yanqing Xue ,&nbsp;Yijiao Xiong ,&nbsp;Wei Huang ,&nbsp;Jianing Liu ,&nbsp;Wen Liu","doi":"10.1039/d5np00018a","DOIUrl":"10.1039/d5np00018a","url":null,"abstract":"<div><div>Covering: 2013–2024</div></div><div><div>Benefiting significantly from recent advances in genome mining, ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products have emerged as a source of chemical inspiration to drive the discovery of therapeutic agents and the development of new biological tools for addressing challenges to synthetic approaches. Despite being confined to twenty proteinogenic amino acid building blocks, the structural complexity and diversity of RiPPs that arise from enzymatic posttranslational modifications (PTMs) surpass expectations and are now believed to be comparable to those produced by non-ribosomal peptide synthetases. Here, we highlight the PTM enzymes characterized over the past decade that engage the –(NH–C_α–CO)_<em>n</em>– repeating units in transformations, particularly those leading to structural rearrangements by peptide backbone remodeling. Unveiling the catalytic mechanisms of these unusual PTM enzymes deepens the understanding in RiPP biosynthesis and, eventually, will enhance our capability of rational design, development and production of functional peptide agents using synthetic biology strategies.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 8","pages":"Pages 1276-1302"},"PeriodicalIF":10.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109175","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 insights into the biosynthesis and biological activities of the peptide-derived redox cofactor mycofactocin†","authors":"Mark Ellerhorst ,&nbsp;Vadim Nikitushkin ,&nbsp;Walid K. Al-Jammal ,&nbsp;Lucas Gregor ,&nbsp;Ivan Vilotijević ,&nbsp;Gerald Lackner","doi":"10.1039/d5np00012b","DOIUrl":"10.1039/d5np00012b","url":null,"abstract":"<div><div>Covering: 2011 to 2025</div></div><div><div>The importance of redox cofactors like nicotinamide adenine dinucleotide or flavin adenine dinucleotide as cofactors for enzymatic reactions in living organisms is widely known. However, many microbial species also employ unusual redox cofactors such as the coenzyme F₄₂₀ or the peptide-derived pyrroloquinoline quinone (PQQ). In this review, we introduce the reader to the recently discovered bacterial redox cofactor mycofactocin (MFT), a valine-tyrosine-derived small molecule of the class of ribosomally synthesized and post-translationally modified peptides (RiPPs) with remarkable biosynthetic and functional similarities to PQQ. The cofactor plays an important role in the reoxidation of non-exchangeable nicotinamide redox cofactors of specialized oxidoreductases in mycobacteria and related actinobacteria. We highlight the bioinformatic discovery of the mycofactocin gene cluster and its auxiliary genes, present strategies for the chemical synthesis of the cofactor, and take a detailed look at the biosynthesis of the glycosylated molecule. Subsequently, the diverse mycofactocin-inducing conditions and associated oxidoreductase families are reviewed, and a potential electron transfer route from high-energy alcohols <em>via</em> mycofactocin to oxygen as a final electron acceptor is presented. The review concludes with a comparison of the physiological roles of PQQ and MFT, and an outlook for future research questions and potential biotechnological applications of mycofactocin.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 8","pages":"Pages 1344-1366"},"PeriodicalIF":10.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075115","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":"Advances in the discovery and study of Trichoderma natural products for biological control applications","authors":"Sophie Jin ,&nbsp;Fabrizio Alberti","doi":"10.1039/d5np00017c","DOIUrl":"10.1039/d5np00017c","url":null,"abstract":"<div><div>Covering: up to 2025</div></div><div><div>Reducing the prevalence of phytopathogens and their impact on crops is essential to reach sustainable agriculture goals. Synthetic pesticides have been commonly used to control crop disease but are now strongly linked to disease resistance, environmental pollution, depletion of soil biodiversity, and bioaccumulation, leading to adverse effects on human health. As a alternative, the prolific <em>Trichoderma</em> genus has been studied for its biocontrol properties, as well as its ability to promote plant growth and increase nutrient uptake. This is done through various mechanisms, one of which is the production of bioactive natural products with high chemical diversity. These include terpenoids, alkaloids, non-ribosomal peptides, polyketides and RiPPs. One of the most studied examples is 6-pentyl-2<em>H</em>-pyran-2-one, a volatile organic polyketide, which induces systemic acquired resistance, morphogenesis, and natural product biosynthesis in plants. Methods for culturing <em>Trichoderma</em> spp., isolating and characterising unique bioactive metabolites are discussed here, with an emphasis on dereplication strategies using metabolomics to optimise discovery. In addition, the role of genome mining for the study of natural product biosynthesis in <em>Trichoderma</em>, and more generally, filamentous fungi is discussed. Examples of bioinformatics tools available to date are listed here with applications in <em>Trichoderma</em> and other ascomycetes. New advances in genome engineering in <em>Trichoderma</em> are also detailed, providing insights into available strategies for the validation of biosynthetic gene clusters identified using genome mining. Finally, the use of a combination of omics approaches, namely metabologenomics, is presented as a growing field for natural product discovery in fungi.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 8","pages":"Pages 1367-1386"},"PeriodicalIF":10.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232716","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":"Synthetic biology strategies for cyanobacterial systems to heterologously produce cyanobacterial natural products","authors":"Manyun Chen ,&nbsp;Dipesh Dhakal ,&nbsp;Campbell W. Eckhardt ,&nbsp;Hendrik Luesch ,&nbsp;Yousong Ding","doi":"10.1039/d5np00009b","DOIUrl":"10.1039/d5np00009b","url":null,"abstract":"<div><div>Covering: 2014 to 2024</div></div><div><div>Cyanobacteria are prolific producers of bioactive natural products, including promising drug leads for FDA-approved cancer therapeutics. Advances in genome sequencing and computational tools have revealed a wealth of cyanobacterial biosynthetic gene clusters (BGCs). However, progress in genome-driven discovery has been hindered by challenges in manipulating native hosts and the limited availability of efficient heterologous expression platforms. This highlight focuses on recent synthetic biology innovations on cyanobacterial systems that address these obstacles, facilitating the production of diverse cyanobacterial natural product families. We discuss key features of widely used cyanobacterial chassis, such as <em>Synechocystis</em> sp. PCC 6803, <em>Synechococcus elongatus</em> UTEX 2973, <em>Anabaena</em> sp. PCC 7120, and emerging hosts. Advances in BGC cloning, combinatorial biosynthesis, transcriptional and translational regulation, and host engineering are also highlighted. Together, these synthetic biology developments provide a powerful framework for expanding cyanobacterial natural product discovery and production.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 8","pages":"Pages 1240-1250"},"PeriodicalIF":10.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951908","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":"Discovery, structure revision, synthesis, and application of all known and even unknown securingine alkaloids","authors":"Chungwoo Lee ,&nbsp;Sunkyu Han","doi":"10.1039/d5np00025d","DOIUrl":"10.1039/d5np00025d","url":null,"abstract":"<div><div>Covering: up to 2025</div></div><div><div>Natural product-based research encompasses the discovery, structure elucidation, biosynthesis, synthesis, and application of naturally occurring secondary metabolites. Securingine alkaloids, isolated from <em>Flueggea suffruticosa</em>, have emerged as valuable molecular frameworks for exploring various aspects of natural product research due to their distinct chemical structures, characterized by unique oxidation and rearrangement patterns. Herein, we provide a comprehensive account of our journey in developing novel synthetic strategies and tactics for accessing all known and even unknown securingines and investigating the potential application of securingine B as a novel class of natural product-based molecular photoswitches.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 8","pages":"Pages 1251-1264"},"PeriodicalIF":10.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256861","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}