Natural Product Reports最新文献

{"title":"Total synthesis of isoflavonoids","authors":"Mamoalosi A. Selepe ,&nbsp;Siyanda T. Mthembu ,&nbsp;Molahlehi S. Sonopo","doi":"10.1039/d4np00060a","DOIUrl":"10.1039/d4np00060a","url":null,"abstract":"<div><div>Covering: 2012 to 2024</div></div><div><div>Isoflavonoids are phenolic compounds with wide structural diversity and a plethora of biological activities. Owing to their structural variation and potential health-promoting and other benefits, they have been targeted for synthesis. Herein, we review the synthesis of natural isoflavonoids belonging to different classes that include isoflavones, isoflavanones, isoflavans, isoflavenes, pterocarpans, rotenoids, coumaronochromones, and coumestans. The synthetic methodologies employed and advancements in synthetic strategies are highlighted.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 3","pages":"Pages 540-591"},"PeriodicalIF":10.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/np/d4np00060a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389554","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":"Enzymatic ester bond formation strategies in fungal macrolide skeletons","authors":"Jin-Mei Zhang, Guan-Yin Yuan and Yi Zou","doi":"10.1039/D4NP00050A","DOIUrl":"10.1039/D4NP00050A","url":null,"abstract":"<p>Covering: up to August 2024</p><p>Macrolides, the core skeletons of numerous marketed drugs and bioactive natural products, have garnered considerable scientific interest owing to their structural diversity and broad spectrum of pharmaceutical activities. The formation of intramolecular ester bonds is a critical biocatalytic step in constructing macrolide skeletons. Here, we summarised enzymatic ester bond formation strategies in fungal polyketide (PK)-type, nonribosomal peptide (NRP)-type, and PK–NRP hybrid-type macrolides. In PK-type macrolides, ester bond formation is commonly catalysed by a <em>trans</em>-acting thioesterase (TE) or a <em>cis</em>-acting TE domain during the product release process. In NRP-type and PK–NRP hybrid-type macrolides, the ester bond is usually introduced through condensation (C) domain-catalysed esterification during the elongation or product release step. Although the TE and C domains share similarities in their catalytic mechanism, using hydroxyl groups as nucleophiles in an intramolecular nucleophilic attack, they differ in terms of the hydroxyl origin, the timing of ester bond formation, and domain location. Furthermore, some TE domains are utilized as chemoenzymatic catalysts to construct macrolides with different ring sizes. A comparison of ester bond formation between fungi and bacteria is also discussed. Exploring the biosynthetic pathways of fungal macrolides, elucidating the diverse strategies employed in the formation of ester bonds, and understanding the application of enzymes/domains in chemoenzymatic synthesis hold promise for the discovery of new bioactive macrolides in the future.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" 2","pages":" 298-323"},"PeriodicalIF":10.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996550","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 role and mechanisms of canonical and non-canonical tailoring enzymes in bacterial terpenoid biosynthesis","authors":"Yuya Kakumu ,&nbsp;Ayesha Ahmed Chaudhri ,&nbsp;Eric J. N. Helfrich","doi":"10.1039/d4np00048j","DOIUrl":"10.1039/d4np00048j","url":null,"abstract":"<div><div>Covering: up to April 2024</div></div><div><div>Terpenoids represent the largest and structurally most diverse class of natural products. According to textbook knowledge, this diversity arises from a two-step biosynthetic process: first, terpene cyclases generate a vast array of mono- and polycyclic hydrocarbon scaffolds with multiple stereocenters from a limited set of achiral precursors, a process extensively studied over the past two decades. Subsequently, tailoring enzymes further modify these complex scaffolds through regio- and stereocontrolled oxidation and other functionalization reactions, a topic of increasing interest in recent years. The resulting highly functionalized terpenoids exhibit a broad spectrum of unique biological activities, making them promising candidates for drug development. Recent advances in genome sequencing technologies along with the development and application of sophisticated genome mining tools have revealed bacteria as a largely untapped resource for the discovery of complex terpenoids. Functional characterization of a limited number of bacterial terpenoid biosynthetic pathways, combined with in-depth mechanistic studies of key enzymes, has begun to reveal the versatility of bacterial enzymatic processes involved in terpenoid modification. In this review, we examine the various tailoring reactions leading to complex bacterial terpenoids. We first discuss canonical terpene-modifying enzymes, that catalyze the functionalization of unactivated C–H bonds, incorporation of diverse functional groups, and oxidative and non-oxidative rearrangements. We then explore non-canonical terpene-modifying enzymes that facilitate oxidative rearrangement, cyclization, isomerization, and dimerization reactions. The increasing number of characterized tailoring enzymes that participate in terpene hydrocarbon scaffold fomation, rather than merely decorating pre-formed scaffolds suggests that a re-evaluation of the traditional two-phase model for terpenoid biosynthesis might be warranted. Finally, we address the potential and challenges of mining bacterial genomes to identify terpene biosynthetic gene clusters and expand the bacterial terpene biosynthetic and chemical space.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 3","pages":"Pages 501-539"},"PeriodicalIF":10.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/np/d4np00048j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078063","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":"Human milk as a complex natural product","authors":"Julie A. Talbert and Steven D. Townsend","doi":"10.1039/D4NP00058G","DOIUrl":"10.1039/D4NP00058G","url":null,"abstract":"<p>Covering: up to the end of 2024</p><p>Breastfeeding is one of the most effective ways to promote child health. However, characterizing the chemistry that fortifies the benefits of breastfeeding remains a grand challenge. Current efforts in the community are focused on characterizing the roles of the different carbohydrates, proteins, and fats in milk. The goal of this review is to highlight and describe current knowledge about the major classes of macromolecules in human milk and their potential role in infant health and wellness.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" 2","pages":" 406-420"},"PeriodicalIF":10.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/np/d4np00058g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996551","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":"The fungal natural product class of the sorbicillinoids: structures, bioactivities, biosynthesis, and synthesis†","authors":"Tobias M. Milzarek ,&nbsp;Tobias A. M. Gulder","doi":"10.1039/d4np00059e","DOIUrl":"10.1039/d4np00059e","url":null,"abstract":"<div><div>Covering 1948 up to October 2024</div></div><div><div>Sorbicillinoids are a growing class of natural products (NPs) that stem from a variety of fungi including members of the orders <em>Hypocreales</em> and <em>Eurotiales</em>. This compound class is unique in its combination of structural complexity and pharmaceutically relevant biological activities. The majority of the sorbicillinoids, which are named after the common hexaketide precursor sorbicillin, exhibit anti-inflammatory, antimicrobial, cytotoxic, phytotoxic, and other selective enzyme inhibitory activities. Over the last eight decades, more than 170 sorbicillinoids, many with strong pharmaceutical potential, have been isolated and described in the literature. This review aims to provide an overview of the structural diversity, biosynthetic pathways, and synthetic studies of this exceptional NP class.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 3","pages":"Pages 482-500"},"PeriodicalIF":10.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/np/d4np00059e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045060","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":"Empowering natural product science with AI: leveraging multimodal data and knowledge graphs†","authors":"David Meijer ,&nbsp;Mehdi A. Beniddir ,&nbsp;Connor W. Coley ,&nbsp;Yassine M. Mejri ,&nbsp;Meltem Öztürk ,&nbsp;Justin J. J. van der Hooft ,&nbsp;Marnix H. Medema ,&nbsp;Adam Skiredj","doi":"10.1039/d4np00008k","DOIUrl":"10.1039/d4np00008k","url":null,"abstract":"<div><div>Artificial intelligence (AI) is accelerating how we conduct science, from folding proteins with AlphaFold and summarizing literature findings with large language models, to annotating genomes and prioritizing newly generated molecules for screening using specialized software. However, the application of AI to emulate human cognition in natural product research and its subsequent impact has so far been limited. One reason for this limited impact is that available natural product data is multimodal, unbalanced, unstandardized, and scattered across many data repositories. This makes natural product data challenging to use with existing deep learning architectures that consume fairly standardized, often non-relational, data. It also prevents models from learning overarching patterns in natural product science. In this Viewpoint, we address this challenge and support ongoing initiatives aimed at democratizing natural product data by collating our collective knowledge into a knowledge graph. By doing so, we believe there will be an opportunity to use such a knowledge graph to develop AI models that can truly mimic natural product scientists' decision-making.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 4","pages":"Pages 654-662"},"PeriodicalIF":10.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986907","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":"Small animals with unique chemistry – the natural product chemistry of Collembola","authors":"Anton Möllerke ,&nbsp;Stefan Schulz","doi":"10.1039/d4np00049h","DOIUrl":"10.1039/d4np00049h","url":null,"abstract":"<div><div>Covering up to September 2024</div></div><div><div>Collembola, commonly known as springtails, are abundant and important members of soil ecosystems. Due to their small size and hidden life, not much is known about their secondary metabolites. This chemistry is remarkably different from that of insects, with which they share a common ancestor, although they diverged already around 450 mya. Here we describe what is known so far, mainly compounds for chemical defence and cuticular lipids, as well as chemical signals. The uniqueness of the structures found is striking, many of which are not known from other natural sources. These include polychlorinated benzopyranones, small alkaloids, hetero-substituted aromatic compounds, and a diverse terpene chemistry, including highly branched compounds.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 4","pages":"Pages 672-680"},"PeriodicalIF":10.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612973","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 the biosynthetic studies of bacterial organoarsenic natural products","authors":"Shotaro Hoshino ,&nbsp;Hiroyasu Onaka ,&nbsp;Ikuro Abe","doi":"10.1039/d4np00036f","DOIUrl":"10.1039/d4np00036f","url":null,"abstract":"<div><div>Covering: 1977 to present</div></div><div><div>Arsenic is widely distributed throughout terrestrial and aquatic environments, mainly in highly toxic inorganic forms. To adapt to environmental inorganic arsenic, bacteria have evolved ubiquitous arsenic metabolic strategies by combining arsenite methylation and related redox reactions, which have been extensively studied. Recent reports have shown that some bacteria have specific metabolic pathways associated with structurally and biologically unique organoarsenic natural products. In this highlight, by exemplifying the cases of oxo-arsenosugars, arsinothricin, and bisenarsan, we summarize recent advances in the identification and biosynthesis of bacterial organoarsenic natural products. We also discuss the potential discoveries of novel arsenic-containing natural products of bacterial origins.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 4","pages":"Pages 663-671"},"PeriodicalIF":10.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078517","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/d5np90011e","DOIUrl":"10.1039/d5np90011e","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 melichuniione A from <em>Melicope chunii</em>.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 4","pages":"Pages 649-653"},"PeriodicalIF":10.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762763","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":"Comparing total chemical synthesis and total biosynthesis routes to fungal specialized metabolites","authors":"Dong-Song Tian ,&nbsp;Xiao Zhang ,&nbsp;Russell J. Cox","doi":"10.1039/d4np00015c","DOIUrl":"10.1039/d4np00015c","url":null,"abstract":"<div><div>Covering the period 1965–2024</div></div><div><div>Total synthesis has been defined as the art and science of making the molecules of living Nature in the laboratory, and by extension, their analogues. At the extremes, specialised metabolites can be created by total chemical synthesis or by total biosynthesis. In this review we explore the advantages and disadvantages of these two approaches using quantitative methodology that combines measures of molecular complexity, molecular weight and fraction of sp³ centres for bioactive fungal metabolites. Total biosynthesis usually involves fewer chemical steps and those steps move more directly to the target than comparable total chemical synthesis. However, total biosynthesis currently lacks the flexibility of chemical synthesis and the ability to easily diversify synthetic routes.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 4","pages":"Pages 720-738"},"PeriodicalIF":10.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981257","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}