Natural Product Reports最新文献

Covering: up to 2025S-Adenosylmethionine (SAM) belongs to the class of group-transferring coenzymes, whereby alkyl group transfers, especially electrophilic methylations, on the one hand, and radical reactions, which are characterised by initial H radical abstractions, on the other hand, are predominant. From an evolutionary point of view, these types of reactions are fundamental e.g. in the modification of nucleobases and fatty acids but also in methionine biosynthesis. At which point of chemical and biological evolution did SAM come into play? Since SAM is closely tied to nucleotide biochemistry both structurally and biosynthetically, a discussion linking it to RNA appears to be reasonably. Apart from general overviews of the early evolutionary role of coenzymes and cofactors, the appearance of SAM on the evolutionary stage has only been dealt with superficially so far. This report attempts to achieve such a classification, both prebiotically and biosynthetically within the RNA world theory.

Covering: up to May 2025C-Methylation is a widespread transformation that occurs in all domains of life. It plays a central role in numerous biological processes and drives the diversification of natural products. These S_N2-type methylation reactions are often catalyzed by S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTs). The frequent occurrence and structural diversity of C-methylated natural products is remarkable, especially considering that carbon is the least electronegative atom that typically serve as a methyl acceptor. Compared to polarizable heteroatoms, C-methylation requires an activation of the carbon atom by an adjacent functional group to form a nucleophilic carbanion and allow nucleophilic attack on the methyl donor SAM. This reactivity can be observed, for example, in activated aromatic compounds. In organic synthesis, direct aromatic methylation remains a challenge as it usually requires stringent conditions that often lead to overalkylation and poor regioselectivity. Nature has developed strategies to facilitate this electrophilic aromatic substitution reaction with remarkable regio- and chemoselectivity, ranging from selective C-monomethylation of ubiquitous molecules such as L-tyrosine to geminal dimethylation of complex polyketides resulting in dearomatization. This comprehensive review highlights the diversity of aromatic SAM-dependent MTs, their versatile substrates, and the resulting natural products.

Covering up to 2025Natural products (NPs) from the terrestrial biodiversity play a key role in oncology drug discovery. While historically identified through bioactivity-guided fractionation, recent advances in high-content screening (HCS) assays, metabolomics, and in silico modeling have significantly enhanced the potential and attractiveness of flora-derived NPs for the development of anticancer therapeutics. This includes immunomodulatory molecules that are able to target the tumor microenvironment to promote immune-mediated clearance of the tumor, thereby improving patient response. This review highlights the untapped potential of molecules extracted from the South Pacific's terrestrial flora in the search for novel antitumor and immunomodulatory compounds. The unique biodiversity of Oceania, including Australia, New Zealand, and Pacific Island Countries and Territories (PICTs) across Micronesia, Melanesia and Polynesia, offers a promising yet largely unexplored reservoir for discovering plant-derived molecules with antitumor and immunomodulatory activities. Herein, we examine the recent pharmacological advances in this field and highlight the need for sustainable and collaborative research. Leveraging cutting-edge technologies could help overcome the challenge of NP-based drug discovery on these geographically isolated islands, unlocking the region's vast potential for plant-derived cancer therapeutics.

Covering: up to the end of August, 2025Spirooxindole-containing natural products are widely distributed in actinomycetes, cyanobacteria, fungi, plants, and invertebrates and have attracted significant attention due to their intricate chemical skeletons and diverse biological activities. Some of these compounds have made substantial contributions to the human health, particularly in the treatment of the central nervous system disorders and cardiovascular conditions as well as in agricultural applications. Accordingly, their biosynthetic pathways have been extensively investigated. Current studies reveal that cytochrome P450 enzymes and flavin-dependent monooxygenases (FMOs) are the primary enzymes involved in triggering carbocation, radical or epoxidation reactions following semipinacol rearrangement during the formation of spirooxindole. In some cases, spontaneous intramolecular Diels-Alder cycloaddition also yields spirooxindole skeletons. This review presents a comprehensive overview of the discovery and structure of spirooxindole alkaloids (SOAs), together with their bioactivities and distinctive biosynthetic pathways.

Covering: up to 2025Amino acid and peptide prenylation leads to a large variety of natural products, including neurotoxins, alkaloids and (non-)ribosomal peptides, with potent bioactivities. The key biosynthetic enzymes are structurally diverse prenyltransferases, which attach short, linear prenyl donors to amino acid acceptor substrates, and show impressive regio- and chemo-selectivity. The emerging number of characterized prenyltransferases, along with their scope, promiscuity, and engineering, provides an expanded chemoenzymatic toolbox for amino acid prenylation and peptide late-stage functionalization with potential in industrial applications such as peptide-based drug development.

Covering: up to the end of 2025Organic synthesis is mastering the newly emerged field of skeletal editing-minimal, core-scaffold rewiring-for the fast and efficient modulation of bioactivity in the pursuit of speeding-up drug discovery. The related goal of modulation of bioactivity by structure modification was evolutionary pursued by microorganisms for ages. In this review, we aim to demonstrate that transformations following skeletal editing logic (such as atom swap/addition/deletion) are already operable by the biosynthetic machinery of actinobacteria. The pathways that are utilized to solve the issues of structure editing are analyzed on the selected examples and organized into four distinct groups, namely, carbon-to-oxygen swaps, carbonyl deletions with ring contraction and fully carbocyclic edits, carbon-to-nitrogen swaps and skeletal reorganizations that retain the atomic formula but alter the connectivity. Most of these transformations are guided by monooxygenase enzymes. Among the diverse skeletal editing cases, the modification of angucycline polyketides, in particular, the ring B modification of dehydrorabelomycin is the most "developed"-disclosed transformations include three types of molecular edits. It displays a close analogy to the diversity-oriented skeletal editing: the action of a single homologous enzyme of the AlpJ family initiates the editing and is able to generate high chemical diversity of the bioactive derivatives. Herein, we also compare the disclosed "natural" skeletal editing strategies with the related "chemical" methods that have emerged in recent years, bridging natural and synthetic repertoires. Further analysis of the separate enzymatic steps and the logic behind them could inspire the development of new reactions and methods for the late-stage modification of complex bioactive molecules.