Natural Product Reports最新文献

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 Melicope chunii.

Covering: 2000 to 2025This review explores the potential of artificial intelligence (AI) in addressing challenges and accelerating molecular insights in biosynthetic pathway research, which is crucial for developing bioactive natural products with applications in pharmacology, agriculture, and biotechnology. It provides an overview of various AI techniques relevant to this research field, including machine learning (ML), deep learning (DL), natural language processing, network analysis, and data mining. AI-powered applications across three main areas, namely, pathway discovery and mining, pathway design, and pathway optimization, are discussed, and the benefits and challenges of integrating omics data and AI for enhanced pathway research are also elucidated. This review also addresses the current limitations, future directions, and the importance of synergy between AI and experimental approaches in unlocking rapid advancements in biosynthetic pathway research. The review concludes with an evaluation of AI's current capabilities and future outlook, emphasizing the transformative impact of AI on biosynthetic pathway research and the potential for new opportunities in the discovery and optimization of bioactive natural products.

Covering: 2000 to 2024The cycloaddition of nitrile oxides with olefins (NOC), followed by reductive cleavage of the resulting isoxazolines, has been widely recognised as a convenient and powerful synthetic strategy for constructing the aldol motif in natural product synthesis. Different modes of NOC (intermolecular, fused and bridged intramolecular) enable the synthesis of diverse isoxazoline products, which can be converted into highly substituted cyclic and acyclic aldol frameworks. This review examines the advances in this field over the past 25 years. More than 50 total syntheses are discussed, encompassing various classes of natural compounds, including macrolides, alkaloids, terpenoids, steroids, pseudosugars, sulfolipids and some others. Moreover, the basic aspects of this methodology are outlined, including methods for the generation of nitrile oxides and isoxazoline ring cleavage, as well as stereochemical models for intramolecular nitrile oxide cycloaddition.

Covering: up to early 2025Privileged compound classes of anti-inflammatory natural products are those where there are many reported members that possess anti-inflammatory properties. The identification of these classes is of particular relevance to drug discovery, as they could serve as valuable starting points in developing effective and safe anti-inflammatory agents. The privileged compound classes of natural products include the polyphenols, coumarins, labdane diterpenoids, sesquiterpene lactones, isoquinoline and indole alkaloids, each offering a variety of molecular scaffolds and functional groups that enable diverse interactions with biological targets. From a medicinal chemistry point of view, natural products are both a boon and a bane. The multi-targeting nature of natural products is a boon in the treatment of multi-factorial diseases such as inflammation, but promiscuity, poor potency and pharmacokinetic properties are significant hurdles that must be addressed to ensure these compounds can be effectively used as therapeutics. In addition, there are continued controversies regarding the efficacies of some of these natural products that will continue to polarise their use. In this review, examples of natural products of six privileged compound classes will be discussed for their potential use and possible further development as anti-inflammatory drugs.

Natural product peptides embody a suite of inherent bioactivities and serve as a template to inspire new chemistries and molecular scaffolds in drug discovery and agrotechnology. Mapping the vast and diverse bioactive peptidome, however, is largely obfuscated by unpredictable molecular transformations in both non-ribosomal sequences and highly post-translationally modified ribosomal protein products. Mass spectrometry is a powerful analytical technique with modern instrumentation achieving unprecedented resolving power, rapid and sensitive gas-phase separations, and versatile multistage fragmentation techniques. As such, mass spectrometry can be (1) leveraged to characterize traditionally difficult-to-sequence natural product peptide modifications via enhanced gas-phase technologies and (2) coupled with complementary 'Omics' approaches to predict peptide structure through transcripts, motifs, biosynthetic pathways, and the biomolecular machinery involved in peptide biogenesis. Herein, the challenges of and recent innovations in mass spectrometry towards the discovery and characterization of natural product bioactive peptides are profiled.

Covering 2015 to 2024Cycloaddition of nitrones with alkenes forms isoxazolidines, which are five-membered heterocycles containing nitrogen and oxygen atoms. This transformation functionalizes alkenes by forming C-C and C-O bonds. The N-O bond in the resultant isoxazolidines is easily cleaved. Additionally, when the cycloaddition is carried out intramolecularly, the regioselectivity of the reaction is influenced by the tether connecting the nitrone and alkene and can differ from the selectivity governed by frontier molecular orbital interaction. These features make the intramolecular cycloaddition of nitrones attractive in the synthesis of complex molecules. In this review, we discuss the intramolecular cycloaddition of nitrones used in the total synthesis of natural products.

Covering: 2019 to 2024Peptide macrocyclization stands as the pivotal step in the biosynthesis journey of bioactive cyclic peptide natural products, spanning both ribosomal and non-ribosomal origins. Beyond the enzymatic N- to C-terminus macrocyclization, natural cyclic peptides frequently display side chain-to-side chain crosslinks, which markedly bolster their stability and biological potency. Traditionally, histidine, with its imidazole side chain, has been regarded as chemically unreactive, leading to relatively sparse reports of histidine-containing crosslinks in cyclic peptide natural products. However, recent advancements in research have illuminated a novel perspective on the role of histidine (His) residues in peptide macrocyclization, revealing that His participation in this process is far more ubiquitous than previously envisioned. This highlight underscores the significance of His-containing crosslinks in natural cyclic peptides and delves into the enzymatic mechanisms underlying their formation.

Covering: 2000 up to the first half of 2024Milk and its derived dairy products have long been integral to the human diet, with evidence of consumption dating back over 9000 years. Milk's high nutritional value renders dairy products an important element of human diet while also offering a fertile environment for microbial growth. Beneficial microorganisms in dairy products are often associated with biogenic and probiotic effects, whereas spoilage or pathogenic microorganisms can pose health risks. Fermentation is a key method to preserve milk. Whereas dairying practices in most parts of the world have been highly altered by industrialization over the past century, nomadic pastoralists in Mongolia notably retain a rich tradition of household-level dairy fermentation that has been practiced since 3000 BC. Milk-associated microorganisms produce a vast number of low molecular weight natural products that can mediate beneficial and detrimental interactions. Bacteria of the genus Pseudomonas are found in traditional Mongolian dairy products and are common contaminants in commercial dairy products, and they can strongly impact the quality and shelf-life of dairy products. These bacteria are well known for their ability to produce a variety of secondary metabolites, including nonribosomal (lipo)peptides, which are both structurally and functionally diverse. Lipopeptides can have antimicrobial properties, act as quorum sensing molecules, and contribute to biofilm formation due to their amphiphilic nature. Although often associated with spoilage, some of these natural products can also exhibit positive effects with potential beneficial applications in the dairy industry. This review aims to provide a comprehensive overview of the interplay between culinary fermentation and the production and activities of microbial-derived natural products.

Covering: 2015 to 2024Mass spectrometry (MS)-based methods have been implemented extensively for enzyme engineering due to their label-free nature, making them suitable for screening a wide range of biochemical systems. Over the past decade, advancements in mass spectrometry, separation science, and the implementation of hyphenated methods have allowed for more streamlined analysis of large volumes of samples while maximizing the richness and dimensionality of the data collected. In this review we highlight recent advancements in mass spectrometry that have allowed for more efficient, robust, and rigorous enzyme engineering for various applications relating to natural products chemistry.

Covering: up to the end of 2024Microbial life dominates the extreme continent Antarctica, playing a pivotal role in ecosystem functioning and serving as a reservoir of specialized metabolites known as natural products (NPs). NPs not only contribute to microbial adaptation to harsh conditions but also modulate microbial community structure. Long-term isolation and environmental pressures have shaped the genomes of Antarctic bacteria, suggesting that they also encode unique NPs. Since NPs are also an important source of drugs, we argue that investigating Antarctic bacterial NPs is essential not only for understanding their ecological role and evolution, but also for discovering new chemical structures, biosynthetic mechanisms, and potential new drugs. Yet, despite advances in omics technologies and increased scientific activities in Antarctica, relatively few new bacterial NPs have been discovered. The lack of systematic research activities focused on the exploration of Antarctic bacteria and their NPs constitutes a big problem considering the climate change issue, to which ecosystems in polar regions are the most sensitive areas on the Earth. Here, we highlight the currently available data on Antarctic bacteria, their biosynthetic potential, and the successful NP discoveries, while addressing the challenges in NP research and advocating for systematic, collaborative efforts aligned with the Antarctic Treaty System and the Antarctic Conservation Biogeographic Regions.