Natural Product Reports最新文献_第5页

Natural products targeting the metabolism of amino acids: from discovery to synthetic development† 针对氨基酸代谢的天然产物：从发现到合成发展。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-07-11 DOI: 10.1039/d5np00039d

Hyun Su Kim , Ahmed H. E. Hassan , Kyuho Moon , Jaehoon Sim

Covering: up to 2025

Amino acids constitute the essential components of biological systems. Over the recent years, there has been a growing interest in exploring amino acid metabolism as a source of novel druggable targets for intractable diseases such as cancer, metabolic disorders, and degenerative diseases. Culminating research has unveiled novel therapeutic targets associated with amino acid metabolism, including glutamine, cysteine, arginine, and tryptophan metabolism. The pursuit of therapeutic drug targets has resulted in the discovery of potential modulators showing promise for the development of new drug candidates. Many of these modulators have been derived from natural products, employing diverse methods such as traditional medical knowledge, high-throughput screening, and bioinformatics approaches. Based on these discoveries, a variety of synthetic analogues have been developed to improve pharmacological profiles, target selectivity, and drug-like properties. Structural optimization of natural product scaffolds, including derivatization, bioisostere incorporation, and prodrug strategies, has enabled the rational design of potent inhibitors targeting amino acid metabolism. These efforts have expanded the utility of naturally occurring inhibitors, offering enhanced efficacy and therapeutic potential. In this review, we systematically categorize natural products that target enzymes involved in amino acid metabolism, highlighting the recent advances in their development as medicinal agents. This work aims to provide a valuable resource for researchers by outlining the therapeutic potential of natural products and identifying opportunities for future investigation.

覆盖范围：至2025年氨基酸构成生物系统的基本组成部分。近年来，人们对探索氨基酸代谢作为治疗顽固性疾病（如癌症、代谢紊乱和退行性疾病）的新型药物靶点越来越感兴趣。最终研究揭示了与氨基酸代谢相关的新治疗靶点，包括谷氨酰胺、半胱氨酸、精氨酸和色氨酸代谢。对治疗药物靶点的追求导致了潜在调节剂的发现，显示了开发新的候选药物的希望。许多这些调节剂来源于天然产物，采用不同的方法，如传统医学知识，高通量筛选和生物信息学方法。基于这些发现，各种合成类似物已经被开发出来，以改善药理学特征，靶标选择性和药物样性质。天然产物支架的结构优化，包括衍生化、生物同位体掺入和前药策略，使得合理设计针对氨基酸代谢的有效抑制剂成为可能。这些努力扩大了天然抑制剂的效用，提供了增强的疗效和治疗潜力。在本文中，我们系统地对氨基酸代谢酶的天然产物进行了分类，重点介绍了它们作为药物开发的最新进展。这项工作旨在通过概述天然产物的治疗潜力和确定未来研究的机会，为研究人员提供宝贵的资源。

{"title":"Natural products targeting the metabolism of amino acids: from discovery to synthetic development†","authors":"Hyun Su Kim , Ahmed H. E. Hassan , Kyuho Moon , Jaehoon Sim","doi":"10.1039/d5np00039d","DOIUrl":"10.1039/d5np00039d","url":null,"abstract":"<div><div>Covering: up to 2025</div></div><div><div>Amino acids constitute the essential components of biological systems. Over the recent years, there has been a growing interest in exploring amino acid metabolism as a source of novel druggable targets for intractable diseases such as cancer, metabolic disorders, and degenerative diseases. Culminating research has unveiled novel therapeutic targets associated with amino acid metabolism, including glutamine, cysteine, arginine, and tryptophan metabolism. The pursuit of therapeutic drug targets has resulted in the discovery of potential modulators showing promise for the development of new drug candidates. Many of these modulators have been derived from natural products, employing diverse methods such as traditional medical knowledge, high-throughput screening, and bioinformatics approaches. Based on these discoveries, a variety of synthetic analogues have been developed to improve pharmacological profiles, target selectivity, and drug-like properties. Structural optimization of natural product scaffolds, including derivatization, bioisostere incorporation, and prodrug strategies, has enabled the rational design of potent inhibitors targeting amino acid metabolism. These efforts have expanded the utility of naturally occurring inhibitors, offering enhanced efficacy and therapeutic potential. In this review, we systematically categorize natural products that target enzymes involved in amino acid metabolism, highlighting the recent advances in their development as medicinal agents. This work aims to provide a valuable resource for researchers by outlining the therapeutic potential of natural products and identifying opportunities for future investigation.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 9","pages":"Pages 1575-1621"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612051","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}

引用次数: 0

Engineering modular enzyme assembly: synthetic interface strategies for natural products biosynthesis applications 工程模块化酶组装：天然产物生物合成应用的合成界面策略。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-07-11 DOI: 10.1039/d5np00027k

Gahyeon Kim , Dukwon Lee , Ji Hun Kim , Seong Do Kim , Hongki Kim , Jae Heon Kim , Sung Sun Yim , Soo-Jin Yeom , Jay D. Keasling , Byung-Kwan Cho

Covering: 2020 to 2025

Natural products remain indispensable sources of therapeutic and bioactive compounds, yet traditional discovery strategies are constrained by compound rediscovery. Modular biosynthetic enzymes, such as type I polyketide synthases (PKSs) and type A non-ribosomal peptide synthetases (NRPSs), offer promising platforms for combinatorial biosynthesis owing to their programmable architectures. However, practical implementation is frequently limited by inter-modular incompatibility and domain-specific interactions. This review highlights recent advances in modular enzyme assembly enabled by synthetic interfaces-including cognate docking domains, synthetic coiled-coils, SpyTag/SpyCatcher, and split inteins-which function as orthogonal, standardized connectors to facilitate post-translational complex formation. These interfaces support rational investigations into substrate specificity, module compatibility, and pathway derivatization as well as general enzyme clustering applications beyond PKS and NRPS systems. Synthetic interfaces can be integrated with computational tools to support a more systematic and scalable framework for modular enzyme engineering by providing predictive insights into domain compatibility and interface design. These approaches within iterative design-build-test-learn workflows can accelerate the programmable assembly of biosynthetic systems and expand the accessible chemical space for natural products.

涵盖：2020年至2025年天然产物仍然是治疗性和生物活性化合物不可或缺的来源，但传统的发现策略受到化合物再发现的限制。模块化生物合成酶，如I型聚酮合成酶（pks）和A型非核糖体肽合成酶（NRPSs），由于其可编程的结构，为组合生物合成提供了有前途的平台。然而，实际实现经常受到模块间不兼容性和特定于领域的交互的限制。本文重点介绍了通过合成界面实现模块化酶组装的最新进展，包括同源对接域、合成线圈、SpyTag/SpyCatcher和分裂intin，它们作为正交的标准化连接器，促进翻译后复合物的形成。这些接口支持对底物特异性、模块兼容性和途径衍生化以及PKS和NRPS系统之外的一般酶聚类应用的合理研究。合成接口可以与计算工具集成，通过提供对域兼容性和接口设计的预测性见解，为模块化酶工程提供更系统化和可扩展的框架。这些迭代设计-构建-测试-学习工作流程中的方法可以加速生物合成系统的可编程组装，并扩大天然产品的可访问化学空间。

{"title":"Engineering modular enzyme assembly: synthetic interface strategies for natural products biosynthesis applications","authors":"Gahyeon Kim , Dukwon Lee , Ji Hun Kim , Seong Do Kim , Hongki Kim , Jae Heon Kim , Sung Sun Yim , Soo-Jin Yeom , Jay D. Keasling , Byung-Kwan Cho","doi":"10.1039/d5np00027k","DOIUrl":"10.1039/d5np00027k","url":null,"abstract":"<div><div>Covering: 2020 to 2025</div></div><div><div>Natural products remain indispensable sources of therapeutic and bioactive compounds, yet traditional discovery strategies are constrained by compound rediscovery. Modular biosynthetic enzymes, such as type I polyketide synthases (PKSs) and type A non-ribosomal peptide synthetases (NRPSs), offer promising platforms for combinatorial biosynthesis owing to their programmable architectures. However, practical implementation is frequently limited by inter-modular incompatibility and domain-specific interactions. This review highlights recent advances in modular enzyme assembly enabled by synthetic interfaces-including cognate docking domains, synthetic coiled-coils, SpyTag/SpyCatcher, and split inteins-which function as orthogonal, standardized connectors to facilitate post-translational complex formation. These interfaces support rational investigations into substrate specificity, module compatibility, and pathway derivatization as well as general enzyme clustering applications beyond PKS and NRPS systems. Synthetic interfaces can be integrated with computational tools to support a more systematic and scalable framework for modular enzyme engineering by providing predictive insights into domain compatibility and interface design. These approaches within iterative design-build-test-learn workflows can accelerate the programmable assembly of biosynthetic systems and expand the accessible chemical space for natural products.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 9","pages":"Pages 1489-1506"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504239","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}

引用次数: 0

Trends in metabolite discovery from Actinomycetes† 放线菌代谢物发现趋势。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-07-11 DOI: 10.1039/d4np00075g

Paolo Monciardini , Matteo Simone , Marianna Iorio , Sonia I. Maffioli , Margherita Sosio , Stefano Donadio

Covering: 2013 to 2023

In this review, we analyzed the scientific literature of the period 2013–2023 that reported novel specialized metabolites from the Actinomycetes, one of the most prolific producers of natural products. The discovered metabolites were categorized on the basis of their chemical originality into two groups: variants of known molecules, or original metabolites. In addition, we subdivided the approaches used to discover these metabolites into four categories: bioassay-based screening, genome mining, metabolome mining, or combinations thereof. We present selected examples of the different approaches used and the resulting original metabolites. Finally, we measure the overall trends of discovery in terms of approaches, of the frequency of original metabolites and of the major biosynthetic classes that have been described. Overall, our analysis indicates that new metabolites continue to be discovered from Actinomycetes at a relatively constant rate and that the frequency of original metabolites seems to be approach-independent and relatively constant within the analyzed time period.

在这篇综述中，我们分析了2013-2023年期间报道的来自放线菌的新型特殊代谢物的科学文献，放线菌是最多产的天然产物之一。发现的代谢物根据其化学原创性分为两组：已知分子的变体或原始代谢物。此外，我们将用于发现这些代谢物的方法细分为四类：基于生物测定的筛选，基因组挖掘，代谢组挖掘或其组合。我们提出了所使用的不同方法和所产生的原始代谢物的选定示例。最后，我们根据方法、原始代谢物的频率和已描述的主要生物合成类别来衡量发现的总体趋势。总的来说，我们的分析表明，新的代谢物继续以相对恒定的速率从放线菌中发现，并且在分析的时间段内，原始代谢物的频率似乎与方法无关且相对恒定。

{"title":"Trends in metabolite discovery from Actinomycetes†","authors":"Paolo Monciardini , Matteo Simone , Marianna Iorio , Sonia I. Maffioli , Margherita Sosio , Stefano Donadio","doi":"10.1039/d4np00075g","DOIUrl":"10.1039/d4np00075g","url":null,"abstract":"<div><div>Covering: 2013 to 2023</div></div><div><div>In this review, we analyzed the scientific literature of the period 2013–2023 that reported novel specialized metabolites from the <em>Actinomycetes</em>, one of the most prolific producers of natural products. The discovered metabolites were categorized on the basis of their chemical originality into two groups: variants of known molecules, or original metabolites. In addition, we subdivided the approaches used to discover these metabolites into four categories: bioassay-based screening, genome mining, metabolome mining, or combinations thereof. We present selected examples of the different approaches used and the resulting original metabolites. Finally, we measure the overall trends of discovery in terms of approaches, of the frequency of original metabolites and of the major biosynthetic classes that have been described. Overall, our analysis indicates that new metabolites continue to be discovered from <em>Actinomycetes</em> at a relatively constant rate and that the frequency of original metabolites seems to be approach-independent and relatively constant within the analyzed time period.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 9","pages":"Pages 1533-1547"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245337","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}

引用次数: 0

Technological developments driving industrial natural product discovery 技术发展推动工业天然产物的发现。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-07-11 DOI: 10.1039/d4np00072b

Richard Lewis , Richard Hammond , Mark Wilkinson , Nick Allenby

Covering: up to 2025

Bacterial natural products have long been the foundation for many therapeutic agents. However, traditional culture-based approaches to discovering these products have been deprioritised by pharmaceutical companies, primarily due to the high rates of rediscovery. To revitalise the pipeline of new drugs, especially antibiotics-an area where natural products have historically played a crucial role-new technologies are essential. Culture-independent, or metagenomic, techniques combined with long-read sequencing technologies are now enabling the identification of novel biosynthetic gene clusters (BGCs). When paired with the heterologous expression of DNA extracted directly from environmental samples (eDNA), these approaches may provide access to untapped microbial biosynthetic diversity. This review explores industrial screening for new compounds and examines how modern technologies such as metagenomics, in situ cultivation, and pico-droplet-based screening are advancing the search for novel natural products. These approaches have the potential to greatly expand the discovery of new bioactive compounds, helping to address the growing need for new therapeutic agents.

长期以来，细菌天然产物一直是许多治疗剂的基础。然而，传统的基于文化的发现这些产品的方法已经被制药公司剥夺了优先权，主要是由于重新发现的比率很高。要使新药，尤其是抗生素——这是一个天然产品历来起着关键作用的领域——的生产渠道恢复活力，新技术是必不可少的。与培养无关或宏基因组技术结合的长读测序技术现在能够鉴定新的生物合成基因簇（bgc）。当与从环境样品中直接提取的DNA （eDNA）的异源表达配对时，这些方法可能提供未开发的微生物生物合成多样性的途径。本文综述了新化合物的工业筛选，并探讨了现代技术如宏基因组学、原位培养和微滴筛选是如何促进寻找新的天然产物的。这些方法有可能极大地扩展新的生物活性化合物的发现，有助于解决对新治疗剂日益增长的需求。

{"title":"Technological developments driving industrial natural product discovery","authors":"Richard Lewis , Richard Hammond , Mark Wilkinson , Nick Allenby","doi":"10.1039/d4np00072b","DOIUrl":"10.1039/d4np00072b","url":null,"abstract":"<div><div>Covering: up to 2025</div></div><div><div>Bacterial natural products have long been the foundation for many therapeutic agents. However, traditional culture-based approaches to discovering these products have been deprioritised by pharmaceutical companies, primarily due to the high rates of rediscovery. To revitalise the pipeline of new drugs, especially antibiotics-an area where natural products have historically played a crucial role-new technologies are essential. Culture-independent, or metagenomic, techniques combined with long-read sequencing technologies are now enabling the identification of novel biosynthetic gene clusters (BGCs). When paired with the heterologous expression of DNA extracted directly from environmental samples (eDNA), these approaches may provide access to untapped microbial biosynthetic diversity. This review explores industrial screening for new compounds and examines how modern technologies such as metagenomics, <em>in situ</em> cultivation, and pico-droplet-based screening are advancing the search for novel natural products. These approaches have the potential to greatly expand the discovery of new bioactive compounds, helping to address the growing need for new therapeutic agents.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 9","pages":"Pages 1507-1532"},"PeriodicalIF":10.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214335","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}

引用次数: 0

Natural products in antiparasitic drug discovery: advances, opportunities and challenges 抗寄生虫药物发现中的天然产物：进展、机遇和挑战。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-07-11 DOI: 10.1039/d5np00007f

Xiaofei Shang , Lixia Dai , Xinyuan Cao , Yudong Ma , Ilgekbayeva Gulnaz , Xiaolou Miao , Xiuhui Li , Xiaorong Yang

Covering: up to 2024.

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.

覆盖范围：至2024年。寄生虫感染了数亿人，造成严重的残疾率和死亡率，并造成毁灭性的社会和经济后果，特别是在发展中国家和地区。几个世纪以来，传统药物一直用于治疗寄生虫病。一些天然产物（NPs）及其衍生物已从这些药物中提取并应用于临床环境，历来引起科学界的关注。近年来，随着革命性技术的发展和应用，从自然资源中发现了更多有前途的化合物，为新型抗寄生虫药物的开发提供了新的可能性。本文综述了从自然资源中开发药物的策略，主要介绍了寄生虫病的病原、流行病学和目前的治疗方法。列出了有前景的NPs及其衍生物，并对其有效性、潜在机理和结构优化进行了描述。随后，讨论了药物开发过程的优点和局限性以及技术在此过程中的作用。本文对基于NPs的抗寄生虫药物的研究与开发进行了展望。高流失率、可及性、可持续供应、知识产权限制等问题仍然阻碍着新产品的发展；然而，奎宁、青蒿素和伊维菌素等经批准的天然产物衍生药物在治疗寄生虫病方面的治疗意义和广泛的临床应用突出表明，天然产物仍然是极有希望的化学制剂储存库。它们独特的结构多样性和显著的生物活性继续激发科学家对新型抗寄生虫药物发现的兴趣。结合最近革命性技术的发展和应用，新产品将为药物发现提供更坚实的基础，并将继续为人类和兽医健康作出重大贡献。

{"title":"Natural products in antiparasitic drug discovery: advances, opportunities and challenges","authors":"Xiaofei Shang , Lixia Dai , Xinyuan Cao , Yudong Ma , Ilgekbayeva Gulnaz , Xiaolou Miao , Xiuhui Li , 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}

引用次数: 0

The ballet of nature: the interconvertible isomerisation of natural products 大自然的芭蕾：天然产物的可转换异构化。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-07-11 DOI: 10.1039/d5np00019j

Ze-Jun Xu , Jing-Jing Han , Chun-Yang Zhang , Hong-Xiang Lou

Covering: up to 2025

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.

天然产物（NPs）之间异构体相互转化的多样性受到内在结构特征和外在环境因素的双重影响，代表了化学复杂性和生物多样性的丰富来源。破译这些复杂的相互转化过程有可能解锁大量生物活性化合物，扩大我们对化学景观的探索。在准确预测“大自然的芭蕾”的同时，确定特定的条件和分子特征将有效地实现更高的活性、更低的毒性和更好的药代动力学。这些进步将大大拓宽它们在医药、农业和工业中有价值的药品和产品开发中的应用。本文全面概述了自然界中成对互转换异构体的起源和化学分类，包括位置异构、互变异构、几何异构、光学异构和构象异构。特别关注这些相互转化过程的形成机制。

{"title":"The ballet of nature: the interconvertible isomerisation of natural products","authors":"Ze-Jun Xu , Jing-Jing Han , Chun-Yang Zhang , 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}

引用次数: 0

Prenylated bacterial natural products: occurrence, chemical diversity, biosynthesis and bioactivity 戊烯基化细菌天然产物：发生、化学多样性、生物合成和生物活性。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-06-19 DOI: 10.1039/d5np00011d

Fan Zhang , Di Zhao , Yuzhu Wu , Lei Li

Covering: 2000 to 2024

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.

戊烯基转移酶（PTs）催化的细菌天然产物（NPs）具有丰富的结构多样性和广泛的生物活性，在新药开发中受到越来越多的关注。本文综述了近年来戊烯酰化细菌NPs的研究进展。为了突出戊酰化细菌NPs的结构和化学空间，我们讨论了它们的发生、结构、生物合成和生物活性。本文总结了具有代表性的例子，并举例说明了不同NP类别的pt催化生物合成途径，这为发现新型戊烯基化细菌NP提供了新的机会。本文综述了细菌NP生物合成过程中PTs的机制研究，认为戊基化细菌NP作为新型生物催化剂在现代医学中具有广阔的应用前景。

引用次数: 0

Hot off the Press 刚出版的。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-06-19 DOI: 10.1039/d5np90029h

Robert A. Hill , Andrew Sutherland

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 Hypericum beanii.

个人选择了32篇最近的论文，介绍了生物有机化学的各个方面的最新发展和新的天然产物，如海丝桃中的海丝桃酮A。

引用次数: 0

Remodeling of ribosomally synthesized peptide backbones based on posttranslational modifications 基于翻译后修饰的核糖体合成肽骨架的重塑。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-06-19 DOI: 10.1039/d5np00018a

Yanqing Xue , Yijiao Xiong , Wei Huang , Jianing Liu , Wen Liu

Covering: 2013–2024

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)_n– 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.

得益于基因组挖掘的最新进展，核糖体合成和翻译后修饰肽（RiPP）天然产物已经成为化学灵感的来源，推动了治疗药物的发现和新生物工具的开发，以应对合成方法的挑战。尽管局限于20个蛋白质原氨基酸构建块，但由酶促翻译后修饰（PTMs）产生的RiPPs的结构复杂性和多样性超出了预期，现在被认为与非核糖体肽合成酶产生的RiPPs相当。在这里，我们重点介绍了在过去十年中表征的PTM酶，这些酶在转化中参与-(nh - c - α- co)n-重复单元，特别是那些通过肽骨架重塑导致结构重排的酶。揭示这些不寻常的PTM酶的催化机制加深了对RiPP生物合成的理解，最终将提高我们利用合成生物学策略合理设计、开发和生产功能肽制剂的能力。

{"title":"Remodeling of ribosomally synthesized peptide backbones based on posttranslational modifications","authors":"Yanqing Xue , Yijiao Xiong , Wei Huang , Jianing Liu , 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<sub>α</sub>–CO)<sub><em>n</em></sub>– 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}

引用次数: 0

Recent insights into the biosynthesis and biological activities of the peptide-derived redox cofactor mycofactocin† 肽衍生的氧化还原辅助因子分枝杆菌素的生物合成和生物活性的最新见解。

IF 10.6 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Natural Product Reports

Pub Date : 2025-06-19 DOI: 10.1039/d5np00012b

Mark Ellerhorst , Vadim Nikitushkin , Walid K. Al-Jammal , Lucas Gregor , Ivan Vilotijević , Gerald Lackner

Covering: 2011 to 2025

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 via 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.

氧化还原辅助因子如烟酰胺腺嘌呤二核苷酸或黄素腺嘌呤二核苷酸作为生物体内酶促反应的辅助因子的重要性已广为人知。然而，许多微生物物种也使用不寻常的氧化还原辅助因子，如辅酶F420或肽衍生的吡咯喹啉醌（PQQ）。在这篇综述中，我们向读者介绍了最近发现的细菌氧化还原辅助因子分枝杆菌素（MFT），这是一种由缬氨酸酪氨酸衍生的小分子，属于核糖体合成和翻译后修饰肽（RiPPs）的一类，与PQQ具有显著的生物合成和功能相似性。该辅助因子在分枝杆菌和相关放线菌中氧化还原酶的非交换性烟酰胺氧化还原辅助因子的再氧化中起重要作用。我们重点介绍了分枝杆菌素基因簇及其辅助基因的生物信息学发现，提出了辅助因子的化学合成策略，并详细介绍了糖基化分子的生物合成。随后，综述了不同的分枝杆菌素诱导条件和相关的氧化还原酶家族，并提出了从高能酒精通过分枝杆菌素到氧作为最终电子受体的潜在电子转移途径。最后对PQQ和MFT的生理作用进行了比较，并对分枝杆菌素未来的研究问题和潜在的生物技术应用前景进行了展望。

{"title":"Recent insights into the biosynthesis and biological activities of the peptide-derived redox cofactor mycofactocin†","authors":"Mark Ellerhorst , Vadim Nikitushkin , Walid K. Al-Jammal , Lucas Gregor , Ivan Vilotijević , 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 F<sub>420</sub> 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}

引用次数: 0