Natural Product Reports最新文献

Covering: 1960s to 2024Harmful algal blooms pose a major threat to aquatic ecosystems and can impact human health. The frequency and intensity of these blooms has increased over recent decades, driven primarily by climate change and an increase in nutrient runoff. Algal blooms often produce toxins that contaminate water sources, disrupt fisheries, and harm human health. These blooms may also result in oxygen-deprived environments leading to mass fish deaths that threaten the survival of other aquatic life. In freshwater and estuarine ecosystems, traditional chemical strategies to mitigate algal blooms include the use of herbicides, metal salts, or oxidants. Though effective, these agents are non-selective, toxic to other species, and cause loss of biodiversity. They can persist in ecosystems, contaminating the food web and providing an impetus for cost-effective, targeted algal-control methods that protect ecosystems. In marine ecosystems, harmful algal blooms are even more challenging to treat due to the lack of scalable solutions and the challenge of dispersal of algal control agents in open ocean settings. Natural products derived from algae-bacteria interactions have led to the evolution of diverse bacteria-derived algaecidal natural products, which are highly potent, species specific and have potential for combating harmful algal blooms. They provide valuable starting points for the development of eco-friendly algae control methods. This review provides a comprehensive overview of all bacterial algaecides and their activities, categorized into two major groups: (1) algaecides produced in ecologically significant associations between bacteria and algae, and (2) algaecides with potentially coincidental activity but without an ecological role in specific bacteria-algae interactions. This review contributes to a better understanding of the chemical ecology of parasitic algal-bacterial interactions, "the warfare under the waves", and highlights the potential applications of bacteria-derived algaecides to provide solutions to harmful algal blooms.

Covering: 2009 up to the end of 2023Stilbenes, an emblematic group of polyphenols, have attracted the attention of numerous researchers owing to their intriguing polycyclic architectures and diverse bioactivities. In this updated review, natural stilbenes were analysed, especially oligomeric stilbenes, which are an emblematic group of polyphenols that harbor intriguing polycyclic architectures and diverse bioactivities compared with those previously anticipated. Oligomeric stilbenes with unique skeletons comprise a large majority of natural stilbenes owing to their structural changes and different substitutions on the phenyl rings. These compounds can be promising sources of lead compounds for studying new drugs and medicines. In addition, the exploration of unusual structures of oligomeric stilbenes such as polyflavanostilbenes A and B, analysing their absolute stereochemistry, and improving their yield using synthetic biology methods have recently gained interest. This review provides a systematic overview of 409 new stilbenes, which were isolated and identified over time from January 2009 to December 2023, focusing on the classification and biomimetic syntheses of oligomeric stilbenes, in addition to presenting meaningful insights into their structural diversity and biological activities, which will inspire further investigations of biological activities, structure-activity relationships, and screening of drug candidates.

Covering 2010-April 2024There have been tremendous new discoveries and developments since 2010 in anticancer research based on marine cyanobacteria. Marine cyanobacteria are prolific sources of anticancer natural products, including the tubulin agents dolastatins 10 and 15 which were originally isolated from a mollusk that feeds on cyanobacteria. Decades of research have culminated in the approval of six antibody-drug conjugates (ADCs) and many ongoing clinical trials. Antibody conjugation has been enabling for several natural products, particularly cyanobacterial cytotoxins. Targeting tubulin dynamics has been a major strategy, leading to the discovery of the gatorbulin scaffold, acting on a new pharmacological site. Cyanobacterial compounds with different mechanisms of action (MOA), targeting novel or validated targets in a range of organelles, also show promise as anticancer agents. Important advances include the development of compounds with novel MOA, including apratoxin and coibamide A analogues, modulating cotranslational translocation at the level of Sec61 in the endoplasmic reticulum, largazole and santacruzamate A targeting class I histone deacetylases, and proteasome inhibitors based on carmaphycins, resembling the approved drug carfilzomib. The pipeline extends with SERCA inhibitors, mitochondrial cytotoxins and membrane-targeting agents, which have not yet advanced clinically since the biology is less understood and selectivity concerns remain to be addressed. In addition, efforts have also focused on the identification of chemosensitizing and antimetastatic agents. The review covers the state of current knowledge of marine cyanobacteria as anticancer agents with a focus on the mechanism, target identification and potential for drug development. We highlight the importance of solving the supply problem through chemical synthesis as well as illuminating the biological activity and in-depth mechanistic studies to increase the value of cyanobacterial natural products to catalyze their development.

Covering: 2014 to 2023 for metabolomics, 2002 to 2023 for information visualizationLC-MS/MS-based untargeted metabolomics is a rapidly developing research field spawning increasing numbers of computational metabolomics tools assisting researchers with their complex data processing, analysis, and interpretation tasks. In this article, we review the entire untargeted metabolomics workflow from the perspective of information visualization, visual analytics and visual data integration. Data visualization is a crucial step at every stage of the metabolomics workflow, where it provides core components of data inspection, evaluation, and sharing capabilities. However, due to the large number of available data analysis tools and corresponding visualization components, it is hard for both users and developers to get an overview of what is already available and which tools are suitable for their analysis. In addition, there is little cross-pollination between the fields of data visualization and metabolomics, leaving visual tools to be designed in a secondary and mostly ad hoc fashion. With this review, we aim to bridge the gap between the fields of untargeted metabolomics and data visualization. First, we introduce data visualization to the untargeted metabolomics field as a topic worthy of its own dedicated research, and provide a primer on cutting-edge visualization research into data visualization for both researchers as well as developers active in metabolomics. We extend this primer with a discussion of best practices for data visualization as they have emerged from data visualization studies. Second, we provide a practical roadmap to the visual tool landscape and its use within the untargeted metabolomics field. Here, for several computational analysis stages within the untargeted metabolomics workflow, we provide an overview of commonly used visual strategies with practical examples. In this context, we will also outline promising areas for further research and development. We end the review with a set of recommendations for developers and users on how to make the best use of visualizations for more effective and transparent communication of results.

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as dicitrinol A from Penicillium citrinum.

Covering: up to 2024.For many years, the value of complex polyketides lay in their medical properties, including their antibiotic and antifungal activities, with little consideration paid to their native functions. However, more recent evidence gathered from the study of inter-organismal interactions has revealed the influence of these metabolites upon the ecological adaptation and distribution of their hosts, as well as their modes of communication. The increasing number of sequenced genomes and associated transcriptomes has also unveiled the widespread occurrence of the underlying biosynthetic enzymes across all kingdoms of life, and the important contributions they make to physiological events specific to each organism. This review depicts the diversity of roles fulfilled by type I polyketides, particularly in light of studies carried out during the last decade, providing an initial overall picture of their diverse functions.

Covering: up to 2024

Fungal pathogens are a major threat to public health, with emerging resistance to all three classes of antifungals that are currently available and increased incidence of invasive fungal infections among hospitalized patients. Ibrexafungerp is a semi-synthetic analog of enfumafungin and the first antifungal agent approved in more than 20 years since the launch of caspofungin, the first of echinocandins. This new drug approval was made possible after a long arduous journey lasting 25 years by dedicated and talented medicinal chemists from two companies that undertook tedious atom-by-atom chemical modification of the natural product enfumafungin, a glycosylated fernane-type triterpenoid isolated from the fungus Hormonema carpetanum. This highlight will cover the discovery of enfumafungin, its biosynthesis and the characterisation of its antifungal profile and mode of action that led to the development of ibrexafungerp. We will discuss the challenges encountered during this long preclinical program and the clinical trial validation of this first-in-class oral antifungal approved to treat vulvovaginal candidiasis with an enormous therapeutic potential to treat future major threatening drug-resistant fungal pathogens.

Covering: 2016 to the end of 2024

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.

Covering: 1974 to 2024Human 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.

Covering: 2010 to 2023Cyanobacterial natural products are a diverse group of molecules with promising biotechnological applications. This review examines the chemical diversity of 995 cyanobacterial metabolites reported from 2010 to 2023. A computational analysis using similarity networking was applied to visualize the chemical space and to compare the diversity of cyanobacterial metabolites among taxonomic orders and environmental sources. Key examples are highlighted, detailing their sources, biological activities, and discovery processes.