Natural Product Reports最新文献

Covering: 1961 to 2024Discovering 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.

Covering: up to 2024Fe(II) 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.

Covering: up to August 2024Enzymes play an essential role in synthesizing value-added chemicals with high specificity and selectivity. Since enzymes utilize substrates derived from renewable resources, biocatalysis offers a pathway to an efficient bioeconomy with reduced environmental footprint. However, enzymes have evolved over millions of years to meet the needs of their host organisms, which often do not align with industrial requirements. As a result, enzymes frequently need to be tailored for specific industrial applications. Combining enzyme engineering with high-throughput screening has emerged as a key approach for developing novel biocatalysts, but several challenges are yet to be addressed. In this review, we explore emergent strategies and methods for isolating, creating, and characterizing enzymes optimized for bioproduction. We discuss fundamental approaches to discovering and generating enzyme variants and identifying those best suited for specific applications. Additionally, we cover techniques for creating libraries using automated systems and highlight innovative high-throughput screening methods that have been successfully employed to develop novel biocatalysts for natural product synthesis.

Covering: 2013 to 2023In an era where antimicrobial resistance severely threatens our ability to treat infections, the discovery of new drugs that belong to different chemical classes and/or bear original modes of action is urgently needed. In this case, diterpenoids comprise a productive field with a proven track record in providing new anti-infectives to tackle bacterial infections and malaria. This review highlights the potential of both naturally occurring and semi-synthetic bi- and tricyclic diterpenoids to become leads in search of new drugs to treat infections caused by bacteria, fungi, viruses and protozoan parasites. The literature from the last decade (2013-2023) is covered, focusing on naturally occurring and semi-synthetic bicyclic (labdanes and labdane-type) and tricyclic (all classes) diterpenoids, detailing their relevant biological activities in the context of infection, which are explained through structure-activity relationships.

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as asperochone A from Aspergillus sp. MMC-2.

Covering: up to June 2024Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites derived from L-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 Papaver somniferum and Coptis japonica 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, e.g., 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.

Covering: 2019 to 2023Isoquinoline alkaloids, an important class of N-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.

Covering: up to March 2024.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.