Natural Product Reports最新文献_第3页

Unleashing the potential: type I CRISPR-Cas systems in actinomycetes for genome editing 释放潜能：放线菌中用于基因组编辑的 I 型 CRISPR-Cas 系统。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-09-18 DOI: 10.1039/d4np00010b

{"title":"Unleashing the potential: type I CRISPR-Cas systems in actinomycetes for genome editing","authors":"","doi":"10.1039/d4np00010b","DOIUrl":"10.1039/d4np00010b","url":null,"abstract":"<div><div>Covering: up to the end of 2023</div></div><div><div>Type I CRISPR-Cas systems are widely distributed, found in over 40% of bacteria and 80% of archaea. Among genome-sequenced actinomycetes (particularly <em>Streptomyces</em> spp.), 45.54% possess type I CRISPR-Cas systems. In comparison to widely used CRISPR systems like Cas9 or Cas12a, these endogenous CRISPR-Cas systems have significant advantages, including better compatibility, wide distribution, and ease of operation (since no exogenous Cas gene delivery is needed). Furthermore, type I CRISPR-Cas systems can simultaneously edit and regulate genes by adjusting the crRNA spacer length. Meanwhile, most actinomycetes are recalcitrant to genetic manipulation, hindering the discovery and engineering of natural products (NPs). The endogenous type I CRISPR-Cas systems in actinomycetes may offer a promising alternative to overcome these barriers. This review summarizes the challenges and recent advances in CRISPR-based genome engineering technologies for actinomycetes. It also presents and discusses how to establish and develop genome editing tools based on type I CRISPR-Cas systems in actinomycetes, with the aim of their future application in gene editing and the discovery of NPs in actinomycetes.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 9","pages":"Pages 1441-1455"},"PeriodicalIF":10.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416726","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

Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids† 植物特化苄基异喹啉生物碱的结构多样性、进化起源和代谢工程。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-09-18 DOI: 10.1039/d4np00029c

Ya Tian , Lingzhe Kong , Qi Li , Yifan Wang , Yongmiao Wang , Zhoujie An , Yuwei Ma , Lixia Tian , Baozhong Duan , Wei Sun , Ranran Gao , Shilin Chen , Zhichao Xu

{"title":"Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids†","authors":"Ya Tian , Lingzhe Kong , Qi Li , Yifan Wang , Yongmiao Wang , Zhoujie An , Yuwei Ma , Lixia Tian , Baozhong Duan , Wei Sun , Ranran Gao , Shilin Chen , Zhichao Xu","doi":"10.1039/d4np00029c","DOIUrl":"10.1039/d4np00029c","url":null,"abstract":"<div><div>Covering: up to June 2024</div></div><div><div>Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites derived from <span>l</span>-tyrosine, exhibiting significant pharmacological properties such as anti-microbial, anti-spasmodic, anti-cancer, cardiovascular protection, and analgesic effects. The industrial production of valuable BIAs relies on extraction from plants; however, challenges concerning their low concentration and efficiency hinder drug development. Hence, alternative approaches, including biosynthesis and chemoenzymatic synthesis, have been explored. Model species like <em>Papaver somniferum</em> and <em>Coptis japonica</em> have played a key role in unraveling the biosynthetic pathways of BIAs; however, many aspects, particularly modified steps like oxidation and methylation, remain unclear. Critical enzymes, <em>e.g.</em>, CYP450s and methyltransferases, play a substantial role in BIA backbone formation and modification, which is essential for understanding the origin and adaptive evolution of these plant specialized metabolites. This review comprehensively analyzes the structural diversity of reported BIAs and their distribution in plant lineages. In addition, the progress in understanding biosynthesis, evolution, and catalytic mechanisms underlying BIA biosynthesis is summarized. Finally, we discuss the progress and challenges in metabolic engineering, providing valuable insights into BIA drug development and the sustainable utilization of BIA-producing plants.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 11","pages":"Pages 1787-1810"},"PeriodicalIF":10.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363530","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

Verticillins: fungal epipolythiodioxopiperazine alkaloids with chemotherapeutic potential 轮状病毒：具有化疗潜力的真菌表多硫酮哌嗪生物碱

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-09-18 DOI: 10.1039/d3np00068k

{"title":"Verticillins: fungal epipolythiodioxopiperazine alkaloids with chemotherapeutic potential","authors":"","doi":"10.1039/d3np00068k","DOIUrl":"10.1039/d3np00068k","url":null,"abstract":"<div><div>Covering: 1970 through June of 2023</div></div><div><div>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.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 9","pages":"Pages 1327-1345"},"PeriodicalIF":10.2,"publicationDate":"2024-09-18","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}

引用次数: 0

Current and emerging tools and strategies for the identification of bioactive natural products in complex mixtures 鉴定复杂混合物中生物活性天然产品的现有和新兴工具与策略

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-09-18 DOI: 10.1039/d4np00006d

Manon Meunier , Andreas Schinkovitz , Séverine Derbré

{"title":"Current and emerging tools and strategies for the identification of bioactive natural products in complex mixtures","authors":"Manon Meunier , Andreas Schinkovitz , Séverine Derbré","doi":"10.1039/d4np00006d","DOIUrl":"10.1039/d4np00006d","url":null,"abstract":"<div><div>Covering: up to 2024</div></div><div><div>The prompt identification of (bio)active natural products (NPs) from complex mixtures poses a significant challenge due to the presence of numerous compounds with diverse structures and (bio)activities. Thus, this review provides an overview of current and emerging tools and strategies for the identification of (bio)active NPs in complex mixtures. Traditional approaches of bioassay-guided fractionation (BGF), followed by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis for compound structure elucidation, continue to play an important role in the identification of active NPs. However, recent advances (2018–2024) have led to the development of novel techniques such as (bio)chemometric analysis, dereplication and combined approaches, which allow efficient prioritization for the elucidation of (bio)active compounds. For researchers involved in the search for bioactive NPs and who want to speed up their discoveries while maintaining accurate identifications, this review highlights the strengths and limitations of each technique and provides up-to-date insights into their combined use to achieve the highest level of confidence in the identification of (bio)active natural products from complex matrices.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 11","pages":"Pages 1766-1786"},"PeriodicalIF":10.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267347","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

Exploring nature's battlefield: organismic interactions in the discovery of bioactive natural products 探索大自然的战场：生物活性天然产品发现过程中的有机体相互作用。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-09-18 DOI: 10.1039/d4np00018h

Yuyang Wang , Yan-Ni Shi , Hao Xiang , Yi-Ming Shi

{"title":"Exploring nature's battlefield: organismic interactions in the discovery of bioactive natural products","authors":"Yuyang Wang , Yan-Ni Shi , Hao Xiang , Yi-Ming Shi","doi":"10.1039/d4np00018h","DOIUrl":"10.1039/d4np00018h","url":null,"abstract":"<div><div>Covering: up to March 2024.</div></div><div><div>Microbial natural products have historically been a cornerstone for the discovery of therapeutic agents. Advanced (meta)genome sequencing technologies have revealed that microbes harbor far greater biosynthetic capabilities than previously anticipated. However, despite the application of CRISPR/Cas-based gene editing and high-throughput technologies to activate silent biosynthetic gene clusters, the rapid identification of new natural products has not led to a proportional increase in the discovery rate of lead compounds or drugs. A crucial issue in this gap may be insufficient knowledge about the inherent biological and physiological functions of microbial natural products. Addressing this gap necessitates recognizing that the generation of functional natural products is deeply rooted in the interactions between the producing microbes and other (micro)organisms within their ecological contexts, an understanding that is essential for harnessing their potential therapeutic benefits. In this review, we highlight the discovery of functional microbial natural products from diverse niches, including those associated with humans, nematodes, insects, fungi, protozoa, plants, and marine animals. Many of these findings result from an organismic-interaction-guided strategy using multi-omic approaches. The current importance of this topic lies in its potential to advance drug discovery in an era marked by increasing antimicrobial resistance.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 11","pages":"Pages 1630-1651"},"PeriodicalIF":10.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/np/d4np00018h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337502","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}

引用次数: 0

Chemical synthesis and functional evaluation of glycopeptides and glycoproteins containing rare glycosyl amino acid linkages 含有稀有糖基氨基酸连接的糖肽和糖蛋白的化学合成和功能评估。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-09-18 DOI: 10.1039/d4np00017j

{"title":"Chemical synthesis and functional evaluation of glycopeptides and glycoproteins containing rare glycosyl amino acid linkages","authors":"","doi":"10.1039/d4np00017j","DOIUrl":"10.1039/d4np00017j","url":null,"abstract":"<div><div>Covering: 1987 to 2023</div></div><div><div>Naturally existing glycoproteins through post-translational protein glycosylation are highly heterogeneous, which not only impedes the structure–function studies, but also hinders the development of their potential medical usage. Chemical synthesis represents one of the most powerful tools to provide the structurally well-defined glycoforms. Being the key step of glycoprotein synthesis, glycosylation usually takes place at serine, threonine, and asparagine residues, leading to the predominant formation of the <em>O</em>- and <em>N</em>-glycans, respectively. However, other amino acid residues containing oxygen, nitrogen, sulfur, and nucleophilic carbon atoms have also been found to be glycosylated. These diverse glycoprotein linkages, occurring from microorganisms to plants and animals, play also pivotal biological roles, such as in cell–cell recognition and communication. The availability of these homogenous rare glycopeptides and glycoproteins can help decipher the glyco-code for developing therapeutic agents. This review highlights the chemical approaches for assembly of the functional glycopeptides and glycoproteins bearing these “rare” carbohydrate–amino acid linkages between saccharide and canonical amino acid residues and their derivatives.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 9","pages":"Pages 1403-1440"},"PeriodicalIF":10.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416725","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

Isolation, biological activity, and synthesis of isoquinoline alkaloids† 异喹啉生物碱的分离、生物活性和合成。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-09-18 DOI: 10.1039/d4np00023d

Xiaorong Yang , Xiaolou Miao , Lixia Dai , Xiao Guo , Janar Jenis , Jiyu Zhang , Xiaofei Shang

{"title":"Isolation, biological activity, and synthesis of isoquinoline alkaloids†","authors":"Xiaorong Yang , Xiaolou Miao , Lixia Dai , Xiao Guo , Janar Jenis , Jiyu Zhang , Xiaofei Shang","doi":"10.1039/d4np00023d","DOIUrl":"10.1039/d4np00023d","url":null,"abstract":"<div><div>Covering: 2019 to 2023</div></div><div><div>Isoquinoline alkaloids, an important class of <em>N</em>-based heterocyclic compounds, have attracted considerable attention from researchers worldwide. To follow up on our prior review (covering 2014–2018) and present the progress of this class of compounds, this review summarizes and provides updated literature on novel isoquinoline alkaloids isolated during the period of 2019–2023, together with their biological activity and underlying mechanisms of action. Moreover, with the rapid development of synthetic modification strategies, the synthesis strategies of isoquinoline alkaloids have been continuously optimized, and the total synthesis of these classes of natural products is reviewed critically herein. Over 250 molecules with a broad range of bioactivities, including antitumor, antibacterial, cardioprotective, anti-inflammatory, neuroprotective and other activities, are isolated and discussed. The total synthesis of more than nine classes of isoquinoline alkaloids is presented, and thirteen compounds constitute the first total synthesis. This survey provides new indications or possibilities for the discovery of new drugs from the original naturally occurring isoquinoline alkaloids.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 11","pages":"Pages 1652-1722"},"PeriodicalIF":10.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/np/d4np00023d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360793","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}

引用次数: 0

Regulation of daptomycin biosynthesis in Streptomyces roseosporus: new insights from genomic analysis and synthetic biology to accelerate lipopeptide discovery and commercial production 玫瑰孢链霉菌中达托霉素生物合成的调控：从基因组分析和合成生物学中获得新见解，加速脂肽的发现和商业化生产

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-09-16 DOI: 10.1039/D4NP00024B

Richard H. Baltz

{"title":"Regulation of daptomycin biosynthesis in Streptomyces roseosporus: new insights from genomic analysis and synthetic biology to accelerate lipopeptide discovery and commercial production","authors":"Richard H. Baltz","doi":"10.1039/D4NP00024B","DOIUrl":"10.1039/D4NP00024B","url":null,"abstract":"<p>Covering 2005–2024</p><p>Daptomycin is a clinically important antibiotic that treats Gram-positive infections of skin and skin structure, bacteremia, and right-sided endocarditis, including those caused by methicillin-resistant <em>Staphylococcus aureus</em> (MRSA). Daptomycin is now generic, and many companies are involved in manufacturing and commercializing this life-saving medicine. There has been much recent interest in improving the daptomycin fermentation of <em>Streptomyces roseosporus</em> by mutagenesis, metabolic engineering, and synthetic biology methods. The genome sequences of two strains discovered and developed at Eli Lilly and Company, a wild-type low-producer and a high-producer induced by <em>N</em>-methyl-<em>N</em>′-nitro-<em>N</em>-nitrosoguanidine (MNNG) mutagenesis, are available for comparitive studies. DNA sequence analysis of the daptomycin biosynthetic gene clusters (BGCs) from these strains indicates that the high producer has two mutations in a large promoter region that drives the transcription of a giant multicistronic mRNA that includes all nine genes involved in daptomycin biosynthesis. The locations of translational start and stop codons strongly suggest that all nine genes are translationally coupled by overlapping stop and start codons or by 70S ribosome scanning. This report also reviews recent studies on this promoter region that have identified at least ten positive or negative regulatory genes suitable to manipulate by metabolic engineering, synthetic biology and focused mutagenesis for strain improvement. Improvements in daptomycin production will also enable high-level production of novel lipopeptide antibiotics identified by genome mining and combinatorial biosynthesis, and accelerate clinical and commercial development of superior lipopeptide antibiotics.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" 12","pages":" 1895-1914"},"PeriodicalIF":10.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267349","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 advances in the biosynthetic studies of bacterial organoarsenic natural products. 细菌有机砷天然产物生物合成研究的最新进展。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-08-28 DOI: 10.1039/d4np00036f

Shotaro Hoshino, Hiroyasu Onaka, Ikuro Abe

引用次数: 0

Empowering natural product science with AI: leveraging multimodal data and knowledge graphs. 用人工智能增强自然产品科学：利用多模态数据和知识图谱。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-08-16 DOI: 10.1039/d4np00008k

David Meijer, Mehdi A Beniddir, Connor W Coley, Yassine M Mejri, Meltem Öztürk, Justin J J van der Hooft, Marnix H Medema, Adam Skiredj

{"title":"Empowering natural product science with AI: leveraging multimodal data and knowledge graphs.","authors":"David Meijer, Mehdi A Beniddir, Connor W Coley, Yassine M Mejri, Meltem Öztürk, Justin J J van der Hooft, Marnix H Medema, Adam Skiredj","doi":"10.1039/d4np00008k","DOIUrl":"10.1039/d4np00008k","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327853/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0