Natural Product Reports最新文献

{"title":"Verticillins: fungal epipolythiodioxopiperazine alkaloids with chemotherapeutic potential","authors":"Herma C. Pierre, Chiraz Soumia M. Amrine, Michael G. Doyle, Amrita Salvi, Huzefa A. Raja, Jonathan R. Chekan, Andrew C. Huntsman, James R. Fuchs, Kebin Liu, Joanna E. Burdette, Cedric J. Pearce and Nicholas H. Oberlies","doi":"10.1039/D3NP00068K","DOIUrl":"10.1039/D3NP00068K","url":null,"abstract":"<p>Covering: 1970 through June of 2023</p><p>Verticillins are epipolythiodioxopiperazine (ETP) alkaloids, many of which possess potent, nanomolar-level cytotoxicity against a variety of cancer cell lines. Over the last decade, their <em>in vivo</em> activity and mode of action have been explored in detail. Notably, recent studies have indicated that these compounds may be selective inhibitors of histone methyltransferases (HMTases) that alter the epigenome and modify targets that play a crucial role in apoptosis, altering immune cell recognition, and generating reactive oxygen species. Verticillin A (<strong>1</strong>) was the first of 27 analogues reported from fungal cultures since 1970. Subsequent genome sequencing identified the biosynthetic gene cluster responsible for producing verticillins, allowing a putative pathway to be proposed. Further, molecular sequencing played a pivotal role in clarifying the taxonomic characterization of verticillin-producing fungi, suggesting that most producing strains belong to the genus <em>Clonostachys</em> (<em>i.e.</em>, <em>Bionectria</em>), Bionectriaceae. Recent studies have explored the total synthesis of these molecules and the generation of analogues <em>via</em> both semisynthetic and precursor-directed biosynthetic approaches. In addition, nanoparticles have been used to deliver these molecules, which, like many natural products, possess challenging solubility profiles. This review summarizes over 50 years of chemical and biological research on this class of fungal metabolites and offers insights and suggestions on future opportunities to push these compounds into pre-clinical and clinical development.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/np/d3np00068k?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617582","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":"Embracing the era of antimicrobial peptides with marine organisms","authors":"Pengyu Chen ,&nbsp;Ting Ye ,&nbsp;Chunyuan Li ,&nbsp;Praveen Praveen ,&nbsp;Zhangli Hu ,&nbsp;Wenyi Li ,&nbsp;Chenjing Shang","doi":"10.1039/d3np00031a","DOIUrl":"10.1039/d3np00031a","url":null,"abstract":"<div><p>Covering: 2018 to Jun of 2023</p></div><div><p>The efficiency of traditional antibiotics has been undermined by the proliferation of antibiotic-resistant pathogenic microorganisms, necessitating the pursuit of innovative therapeutic agents. Antimicrobial peptides (AMPs), which are part of host defence peptides found ubiquitously in nature, exhibiting a wide range of activity towards bacteria, fungi, and viruses, offer a highly promising candidate solution. The efficacy of AMPs can frequently be augmented <em>via</em> alterations to their amino acid sequences or structural adjustments. Given the vast reservoir of marine life forms and their distinctive ecosystems, marine AMPs stand as a burgeoning focal point in the quest for alternative peptide templates extracted from natural sources. Advances in identification and characterization techniques have accelerated the discoveries of marine AMPs, thereby stimulating AMP customization, optimization, and synthesis research endeavours. This review presents an overview of recent discoveries related to the intriguing qualities of marine AMPs. Emphasis will be placed upon post-translational modifications (PTMs) of marine AMPs and how they may impact functionality and potency. Additionally, this review considers ways in which marine PTM might support larger-scale, heterologous AMP manufacturing initiatives, providing insights into translational applications of these important biomolecules.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41090050","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":"Chemistry and biology of specialized metabolites produced by Actinomadura","authors":"Yousef Dashti ,&nbsp;Jeff Errington","doi":"10.1039/d3np00047h","DOIUrl":"10.1039/d3np00047h","url":null,"abstract":"<div><p>Covering: up to the end of 2022</p></div><div><p>In recent years rare Actinobacteria have become increasingly recognised as a rich source of novel bioactive metabolites. <em>Actinomadura</em> are Gram-positive bacteria that occupy a wide range of ecological niches. This review highlights about 230 secondary metabolites produced by <em>Actinomadura</em> spp., reported until the end of 2022, including their bioactivities and selected biosynthetic pathways. Notably, the bioactive compounds produced by <em>Actinomadura</em> spp. demonstrate a wide range of activities, including antimicrobial, antitumor and anticoccidial effects, highlighting their potential in various fields.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138681480","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":"Harnessing the potential: advances in cyanobacterial natural product research and biotechnology†","authors":"Martin Baunach ,&nbsp;Arthur Guljamow ,&nbsp;María Miguel-Gordo ,&nbsp;Elke Dittmann","doi":"10.1039/d3np00045a","DOIUrl":"10.1039/d3np00045a","url":null,"abstract":"<div><p>Covering: 2000 to 2023</p></div><div><p>Cyanobacteria produce a variety of bioactive natural products that can pose a threat to humans and animals as environmental toxins, but also have potential for or inspire pharmaceutical use. As oxygenic phototrophs, cyanobacteria furthermore hold great promise for sustainable biotechnology. Yet, the necessary tools for exploiting their biotechnological potential have so far been established only for a few model strains of cyanobacteria, while large untapped biosynthetic resources are hidden in slow-growing cyanobacterial genera that are difficult to access by genetic techniques. In recent years, several approaches have been developed to circumvent the bottlenecks in cyanobacterial natural product research. Here, we summarize current progress that has been made in unlocking or characterizing cryptic metabolic pathways using integrated omics techniques, orphan gene cluster activation, use of genetic approaches in original producers, heterologous expression and chemo-enzymatic techniques. We are mainly highlighting genomic mining concepts and strategies towards high-titer production of cyanobacterial natural products from the last 10 years and discuss the need for further research developments in this field.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138581239","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":"Class II terpene cyclases: structures, mechanisms, and engineering","authors":"Xingming Pan ,&nbsp;Jeffrey D. Rudolf ,&nbsp;Liao-Bin Dong","doi":"10.1039/d3np00033h","DOIUrl":"10.1039/d3np00033h","url":null,"abstract":"<div><p>Covering: up to July 2023</p></div><div><p>Terpene cyclases (TCs) catalyze some of the most complicated reactions in nature and are responsible for creating the skeletons of more than 95 000 terpenoid natural products. The canonical TCs are divided into two classes according to their structures, functions, and mechanisms. The class II TCs mediate acid–base-initiated cyclization reactions of isoprenoid diphosphates, terpenes without diphosphates (<em>e.g.</em>, squalene or oxidosqualene), and prenyl moieties on meroterpenes. The past twenty years witnessed the emergence of many class II TCs, their reactions and their roles in biosynthesis. Class II TCs often act as one of the first steps in the biosynthesis of biologically active natural products including the gibberellin family of phytohormones and fungal meroterpenoids. Due to their mechanisms and biocatalytic potential, TCs elicit fervent attention in the biosynthetic and organic communities and provide great enthusiasm for enzyme engineering to construct novel and bioactive molecules. To engineer and expand the structural diversities of terpenoids, it is imperative to fully understand how these enzymes generate, precisely control, and quench the reactive carbocation intermediates. In this review, we summarize class II TCs from nature, including sesquiterpene, diterpene, triterpene, and meroterpenoid cyclases as well as noncanonical class II TCs and inspect their sequences, structures, mechanisms, and structure-guided engineering studies.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138743634","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 pearl jubilee of microcin J25: thirty years of research on an exceptional lasso peptide","authors":"Fernando Baquero ,&nbsp;Konstantinos Beis ,&nbsp;David J. Craik ,&nbsp;Yanyan Li ,&nbsp;A. James Link ,&nbsp;Sylvie Rebuffat ,&nbsp;Raúl Salomón ,&nbsp;Konstantin Severinov ,&nbsp;Séverine Zirah ,&nbsp;Julian D. Hegemann","doi":"10.1039/d3np00046j","DOIUrl":"10.1039/d3np00046j","url":null,"abstract":"<div><p>Covering: 1992 up to 2023</p></div><div><p>Since their discovery, lasso peptides went from peculiarities to be recognized as a major family of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products that were shown to be spread throughout the bacterial kingdom. Microcin J25 was first described in 1992, making it one of the earliest known lasso peptides. No other lasso peptide has since then been studied to such an extent as microcin J25, yet, previous review articles merely skimmed over all the research done on this exceptional lasso peptide. Therefore, to commemorate the 30th anniversary of its first report, we give a comprehensive overview of all literature related to microcin J25. This review article spans the early work towards the discovery of microcin J25, its biosynthetic gene cluster, and the elucidation of its three-dimensional, threaded lasso structure. Furthermore, the current knowledge about the biosynthesis of microcin J25 and lasso peptides in general is summarized and a detailed overview is given on the biological activities associated with microcin J25, including means of self-immunity, uptake into target bacteria, inhibition of the Gram-negative RNA polymerase, and the effects of microcin J25 on mitochondria. The <em>in vitro</em> and <em>in vivo</em> models used to study the potential utility of microcin J25 in a (veterinary) medicine context are discussed and the efforts that went into employing the microcin J25 scaffold in bioengineering contexts are summed up.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139072689","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 incredible story of ophiobolin A and sphaeropsidin A: two fungal terpenes from wilt-inducing phytotoxins to promising anticancer compounds†‡","authors":"Antonio Evidente","doi":"10.1039/d3np00035d","DOIUrl":"10.1039/d3np00035d","url":null,"abstract":"<div><p>Covering: 2000 to 2023</p></div><div><p>This review presents the exceptional story of ophiobolin A (OphA) and sphaeropsidin A (SphA), a sesterterpene and a diterpene, respectively, which were initially isolated as fungal phytotoxins and subsequently shown to possess other interesting biological activities, including promising anticancer activities. Ophiobolin A is a phytotoxin produced by different fungal pathogens, all belonging to the <em>Bipolaris</em> genus. Initially, it was only known as a very dangerous phytotoxin produced by fungi attacking essential cereals, such as rice and barley. However, extensive and interesting studies were carried out to define its original carbon skeleton, which is characterized by a typical 5 : 8 : 5 ring system and shared with fusicoccins and cotylenins, and its phytotoxic activity on host and non-host plants. The biosynthesis of OphA was also defined by describing the different steps starting from mevalonate and through the rearrangement of the acyclic C-25 precursor lead the toxin is obtained. OphA was also produced as a bioherbicide from <em>Drechslera gigantea</em> and proposed for the biocontrol of the widespread and dangerous weed <em>Digitaria sanguinaria</em>. To date, more than sixty ophiobolins have been isolated from different fungi and their biological activities and structure–activity relationship investigated, which were also described using their hemisynthetic derivatives. In the last two decades, thorough studies have been performed on the potential anticancer activity of OphA and its original mode of action, attracting great interest from scientists. Sphaeropsidin A has a similar story. It was isolated as the main phytotoxin from <em>Diplodia cupressi</em>, the causal agent of Italian cypress canker disease, resulting in the loss of millions of plants in a few years in the Mediterranean basin. The damage to the forest, environment and ornamental heritage are noteworthy and economic losses are also suffered by tree nurseries and the wood industry. Six natural analogues of SphA were isolated and several interesting hemisynthetic derivatives were prepared to study its structure–activity relationship. Surprisingly, sphaeropsidin A showed other interesting biological activities, including antibiotic, antifungal, and antiviral. In the last decade, extensive studies have focused on the anticancer activity and original mode of action of SphA. Furthermore, specific hemisynthetic studies enable the preparation of derivatives of SphA, preserving its chromophore, which showed a noteworthy increase in anticancer activity. It has been demonstrated that ophiobolin A and sphaeropsidin A are promising natural products showing potent activity against some malignant cancers, such as brain glioblastoma and different melanomas.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827258","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 oxidative phenol coupling for the total synthesis of natural products","authors":"Matthew C. Carson ,&nbsp;Marisa C. Kozlowski","doi":"10.1039/d3np00009e","DOIUrl":"10.1039/d3np00009e","url":null,"abstract":"<div><p>Covering: 2008 to 2023</p></div><div><p>This review will describe oxidative phenol coupling as applied in the total synthesis of natural products. This review covers catalytic and electrochemical methods with a brief comparison to stoichiometric and enzymatic systems assessing their practicality, atom economy, and other measures. Natural products forged by C–C and C–O oxidative phenol couplings as well as from alkenyl phenol couplings will be addressed. Additionally, exploration into catalytic oxidative coupling of phenols and other related species (carbazoles, indoles, aryl ethers, <em>etc.</em>) will be surveyed. Future directions of this particular area of research will also be assessed.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9598950","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 asymmetric synthesis of natural products bearing an α-tertiary amine moiety via temporary chirality induction strategies","authors":"Hongjun Jeon ,&nbsp;Jae Hyun Kim ,&nbsp;Sanghee Kim","doi":"10.1039/d3np00032j","DOIUrl":"10.1039/d3np00032j","url":null,"abstract":"<div><p>Covering: 2013 to 2023</p></div><div><p>The α-tertiary amine moiety is a common structural motif in natural alkaloids and is frequently associated with intriguing biological activities and inherent synthetic challenges. A major hurdle in the total synthesis of these alkaloids is the asymmetric construction of the α-tertiary amine moiety. Temporary chirality inductions have been effective strategies employed to address this issue, particularly in natural product synthesis. The temporary chirality induction strategies in α-tertiary amine synthesis can be broadly classified into three categories based on the types of temporary chirality involved: Seebach's self-regeneration of stereocenters (SRS), C-to-N-to-C chirality transfer, and memory of chirality (MOC). This review highlights the recent advancements in temporary chirality induction strategies for the total synthesis of α-tertiary amine-containing natural products between 2013 and 2023.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230573","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":"Marine natural products†","authors":"Anthony R. Carroll ,&nbsp;Brent R. Copp ,&nbsp;Tanja Grkovic ,&nbsp;Robert A. Keyzers ,&nbsp;Michèle R. Prinsep","doi":"10.1039/d3np00061c","DOIUrl":"10.1039/d3np00061c","url":null,"abstract":"<div><p>Covering: January to the end of December 2022</p></div><div><p>This review covers the literature published in 2022 for marine natural products (MNPs), with 645 citations (633 for the period January to December 2022) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, the submerged parts of mangroves and other intertidal plants. The emphasis is on new compounds (1417 in 384 papers for 2022), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. An analysis of NP structure class diversity in relation to biota source and biome is discussed.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569197","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}