Natural Product Reports最新文献_第10页

Debottlenecking cytochrome P450-dependent metabolic pathways for the biosynthesis of commercial natural products 去瓶颈化细胞色素 P450 依赖性代谢途径，促进商业天然产品的生物合成。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-18 DOI: 10.1039/d4np00027g

Susanne M. Germann , Maxence Holtz , Michael Krogh Jensen , Carlos G. Acevedo-Rocha

{"title":"Debottlenecking cytochrome P450-dependent metabolic pathways for the biosynthesis of commercial natural products","authors":"Susanne M. Germann , Maxence Holtz , Michael Krogh Jensen , Carlos G. Acevedo-Rocha","doi":"10.1039/d4np00027g","DOIUrl":"10.1039/d4np00027g","url":null,"abstract":"<div><div>Covering: 2016 to the end of 2024</div></div><div><div>This highlight article aims to provide a perspective on the challenges that novel biotechnological processes face in the biomanufacturing of natural products (NPs) whose biosynthesis pathways rely on cytochrome P450 monooxygenases. This enzyme superfamily is one of the most versatile in the biosynthesis of a plethora of NPs finding use across the food, nutrition, medicine, chemical and cosmetics industries. These enzymes often exhibit excellent regio- and stereoselectivity, but they can suffer from low activity and instability, which are serious issues impairing the development of high performing bioprocesses. We start with a brief introduction to industrial biotechnology and the importance of looking for alternative means for producing NPs independently from unsustainable fossil fuels or plant extractions. We then discuss the challenges and implemented solutions during the development of commercial NP processes focusing on the P450-dependent steps primarily in yeast cell factories. Our main focus is to highlight the challenges often encountered when utilizing P450-dependent NP pathways, and how protein engineering can be used for debottlenecking them. Finally, we briefly touch upon the importance of artificial intelligence and machine learning for guiding engineering efforts.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 12","pages":"Pages 1846-1857"},"PeriodicalIF":10.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646136","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

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 : 2024-11-18 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":"<div><div>Covering 2005–2024</div></div><div><div>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.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 12","pages":"Pages 1895-1914"},"PeriodicalIF":10.2,"publicationDate":"2024-11-18","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

Scaling up for success: from bioactive natural products to new medicines 扩大规模，取得成功：从生物活性天然产品到新药。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-18 DOI: 10.1039/d4np00022f

Maximilian J. Helf , Kathrin Buntin , Andrej Klančar , Michael Rust , Frank Petersen , Dominik Pistorius , Eric Weber , Joanne Wong , Philipp Krastel

{"title":"Scaling up for success: from bioactive natural products to new medicines","authors":"Maximilian J. Helf , Kathrin Buntin , Andrej Klančar , Michael Rust , Frank Petersen , Dominik Pistorius , Eric Weber , Joanne Wong , Philipp Krastel","doi":"10.1039/d4np00022f","DOIUrl":"10.1039/d4np00022f","url":null,"abstract":"<div><div>Covering 1986 to present</div></div><div><div>Natural product drug discovery at Novartis has a long and successful history of delivering life saving medicines to millions of patients. In this viewpoint, we are presenting the tools we use and challenges we face as we advance natural products from early research into development and beyond. We are leveraging our collection of 90 000 microbial strains and 20 000 isolated natural products to find new medications in an interdisciplinary approach that requires expertise in microbiology, computational biology, synthetic biology, chemistry, and process development. Technological advances, particularly in genome engineering and data science have transformed our field, accelerating discovery and facilitating sustainable compound supply. Emerging new modalities such as antibody drug conjugates, radioligand therapies and xRNA-based medications offer new opportunities for natural product-derived drugs. By taking advantage of these new modalities and the most recent research technologies, natural products will significantly contribute to the medicines of the future.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"41 12","pages":"Pages 1824-1834"},"PeriodicalIF":10.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915514","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

Chemical case studies from natural products of recent interest in the crop protection industry 作物保护行业近期关注的天然产品化学案例研究

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-18 DOI: 10.1039/d4np00035h

Georg Späth , Olivier Loiseleur

引用次数: 0

Human microbiota peptides: important roles in human health 人类微生物群肽：在人类健康中的重要作用。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-14 DOI: 10.1039/d4np00042k

Abdul Bari Shah , Sang Hee Shim

{"title":"Human microbiota peptides: important roles in human health","authors":"Abdul Bari Shah , Sang Hee Shim","doi":"10.1039/d4np00042k","DOIUrl":"10.1039/d4np00042k","url":null,"abstract":"<div><div>Covering: 1974 to 2024</div></div><div><div>Human microbiota consist of a diverse array of microorganisms, such as bacteria, Eukarya, archaea, and viruses, which populate various parts of the human body and live in a cooperatively beneficial relationship with the host. They play a crucial role in supporting the functional balance of the microbiome. The coevolutionary progression has led to the development of specialized metabolites that have the potential to substitute traditional antibiotics in combating global health challenges. Although there has been a lot of research on the human microbiota, there is a considerable lack of understanding regarding the wide range of peptides that these microbial populations produce. Particularly noteworthy are the antibiotics that are uniquely produced by the human microbiome, especially by bacteria, to protect against invasive infections. This review seeks to fill this knowledge gap by providing a thorough understanding of various peptides, along with their in-depth biological importance in terms of human disorders. Advancements in genomics and the understanding of molecular mechanisms that control the interactions between microbiota and hosts have made it easier to find peptides that come from the human microbiome. We hope that this review will serve as a basis for developing new therapeutic approaches and personalized healthcare strategies. Additionally, it emphasizes the significance of these microbiota in the field of natural product discovery and development.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 1","pages":"Pages 151-194"},"PeriodicalIF":10.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612972","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

Fe(ii) and 2-oxoglutarate-dependent dioxygenases for natural product synthesis: molecular insights into reaction diversity 用于天然产物合成的铁(II)和 2-氧代戊二酸二氧酶：对反应多样性的分子认识。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-14 DOI: 10.1039/d4np00030g

Songyin Zhao , Lunjie Wu , Yan Xu , Yao Nie

{"title":"Fe(ii) and 2-oxoglutarate-dependent dioxygenases for natural product synthesis: molecular insights into reaction diversity","authors":"Songyin Zhao , Lunjie Wu , Yan Xu , Yao Nie","doi":"10.1039/d4np00030g","DOIUrl":"10.1039/d4np00030g","url":null,"abstract":"<div><div>Covering: up to 2024</div></div><div><div>Fe(<span>ii</span>) and 2-oxoglutarate-dependent dioxygenases (Fe/2OG DOs) are a superfamily of enzymes that play important roles in a variety of catalytic reactions, including hydroxylation, ring formation, ring reconstruction, desaturation, and demethylation. Each member of this family has similarities in their overall structure, but they have varying specific differences, making Fe/2OG DOs attractive for catalytic diversity. With the advancement of current research, more Fe/2OG DOs have been discovered, and their catalytic scope has been further broadened; however, apart from hydroxylation, many reaction mechanisms have not been accurately demonstrated, and there is a lack of a systematic understanding of their molecular basis. Recently, an increasing number of X-ray structures of Fe/2OG DOs have provided new insights into the structural basis of their function and substrate-binding properties. This structural information is essential for understanding catalytic mechanisms and mining potential catalytic reactions. In this review, we summarize most of the Fe/2OG DOs whose structures have been resolved in recent years, focus on their structural features, and explore the relationships between various structural elements and unique catalytic mechanisms and their associated reaction type classification.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 1","pages":"Pages 67-92"},"PeriodicalIF":10.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453667","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

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-14 DOI: 10.1039/d4np00025k

Shengxin Sun , Xia Wang , Nvdan Hu , Shiqi Fu , Shengkun Li

{"title":"Siccanin-related drimane meroterpenoids: biological activities and synthesis†‡","authors":"Shengxin Sun , Xia Wang , Nvdan Hu , Shiqi Fu , Shengkun Li","doi":"10.1039/d4np00025k","DOIUrl":"10.1039/d4np00025k","url":null,"abstract":"<div><div>Covering: 1962 to 2023</div></div><div><div>Drimane (hydro)quinones biosynthetically arise from the combination of drimane-type terpenoids with phenols or equivalents. Since the isolation of siccanin in 1962 (structure identified in 1967), over 200 natural drimane (hydro)quinones have been reported. They are widespread with remarkably diverse architectures and biological functions, which are achieved by varying either the drimane subunit, hydroquinone segment, or the fusion types of drimane and hydroquinone segment both of them. This type of natural products has drawn increasing attention in the discovery of novel pharmaceutical leads. Enormous efforts have been devoted to developing efficient and divergent synthesis approaches to facilitate the SAR study of drimane (hydro)quinones, aiming for more promising functional leads. This review is arranged mainly in terms of scaffold types of drimane (hydro)quinones and further categorized on the basis of biological functions. The mechanisms of action are also briefly discussed. Synthetic methods are categorized according to the strategies forging the Csp<sup>2</sup>–Csp<sup>3</sup> linker between drimane segments and (hydro)quinone subunits.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 1","pages":"Pages 113-150"},"PeriodicalIF":10.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566518","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

Chemical diversity of cyanobacterial natural products† 蓝藻天然产品的化学多样性。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-14 DOI: 10.1039/d4np00040d

Márcio B. Weiss , Ricardo M. Borges , Peter Sullivan , João P. B. Domingues , Francisco H. S. da Silva , Victória G. S. Trindade , Shangwen Luo , Jimmy Orjala , Camila M. Crnkovic

引用次数: 0

Volatile organic compounds (VOCs) in terrestrial extreme environments: implications for life detection beyond Earth 陆地极端环境中的挥发性有机化合物（VOCs）：对地球以外生命探测的影响。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-14 DOI: 10.1039/d4np00037d

Claire A. Batty , Victoria K. Pearson , Karen Olsson-Francis , Geraint Morgan

{"title":"Volatile organic compounds (VOCs) in terrestrial extreme environments: implications for life detection beyond Earth","authors":"Claire A. Batty , Victoria K. Pearson , Karen Olsson-Francis , Geraint Morgan","doi":"10.1039/d4np00037d","DOIUrl":"10.1039/d4np00037d","url":null,"abstract":"<div><div>Covering: 1961 to 2024</div></div><div><div>Discovering and identifying unique natural products/biosignatures (signatures that can be used as evidence for past or present life) that are abundant, and complex enough that they indicate robust evidence of life is a multifaceted process. One distinct category of biosignatures being explored is organic compounds. A subdivision of these compounds not yet readily investigated are volatile organic compound (VOCs). When assessing these VOCs as a group (volatilome) a fingerprint of all VOCs within an environment allows the complex patterns in metabolic data to be unravelled. As a technique already successfully applied to many biological and ecological fields, this paper explores how analysis of volatilomes in terrestrial extreme environments could be used to enhance processes (such as metabolomics and metagenomics) already utilised in life detection beyond Earth. By overcoming some of the complexities of collecting VOCs in remote field sites, a variety of lab based analytical equipment and techniques can then be utilised. Researching volatilomics in astrobiology requires time to characterise the patterns of VOCs. They must then be differentiated from abiotic (non-living) signals within extreme environments similar to those found on other planetary bodies (analogue sites) or in lab-based simulated environments or microcosms. Such an effort is critical for understanding data returned from past or upcoming missions, but it requires a step change in approach which explores the volatilome as a vital additional tool to current ‘Omics techniques.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 1","pages":"Pages 93-112"},"PeriodicalIF":10.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/np/d4np00037d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453668","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

Synthetic-bioinformatic natural product-inspired peptides† 合成生物信息学天然产品启发肽。

IF 10.2 1区化学

Natural Product Reports Pub Date : 2024-11-14 DOI: 10.1039/d4np00043a

Samantha Nelson , Elizabeth I. Parkinson

{"title":"Synthetic-bioinformatic natural product-inspired peptides†","authors":"Samantha Nelson , Elizabeth I. Parkinson","doi":"10.1039/d4np00043a","DOIUrl":"10.1039/d4np00043a","url":null,"abstract":"<div><div>Covering: 2016 to 2024</div></div><div><div>Natural products, particularly cyclic peptides, are a promising source of bioactive compounds. Nonribosomal peptide synthetases (NRPSs) play a key role in biosynthesizing these compounds, which include antibiotic and anticancer agents, immunosuppressants, and others. Traditional methods of discovering natural products have limitations including cryptic biosynthetic gene clusters (BGCs), low titers, and currently unculturable organisms. This has prompted the exploration of alternative approaches. Synthetic-bioinformatic natural products (<em>syn</em>-BNPs) are one such alternative that utilizes bioinformatics techniques to predict nonribosomal peptides (NRPs) followed by chemical synthesis of the predicted peptides. This approach has shown promise, resulting in the discovery of a variety of bioactive compounds including peptides with antibacterial, antifungal, anticancer, and proteasome-stimulating activities. Despite the success of this approach, challenges remain especially in the accurate prediction of fatty acid incorporation, tailoring enzyme modifications, and peptide release mechanisms. Further work in these areas will enable the discovery of many bioactive peptides that are currently inaccessible.</div></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":"42 1","pages":"Pages 50-66"},"PeriodicalIF":10.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542952","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