Natural Product Reports最新文献

Covering: 1966 to 2026γ-Amino acids are structurally diverse non-proteinogenic building blocks that endow bacterial natural products with unique conformational, physicochemical, and biological properties. Although individual γ-amino acid-containing metabolites have been extensively investigated, their structural diversity, biosynthetic origins, and functional significance have rarely been considered from a unified perspective. Here, we review nearly six decades of research on bacterial γ-amino acid-containing natural products, covering from 1966 and the discovery of bleomycin to genome-guided discoveries in 2026. We discuss the major structural classes of γ-amino acids, including GABA-derived, β-keto, statine-type, vinylogous, fully reduced, and masked amino acid-derived motifs, and highlight how these building blocks are generated through primary metabolism, hybrid NRPS-PKS assembly lines, and specialized tailoring reactions. Particular emphasis is placed on the relationships between γ-amino acid structure, biosynthetic logic, and biological function, including their roles in protease inhibition, covalent target engagement, metallophore activity, and microbial ecology. Finally, we discuss emerging opportunities for genome mining and biosynthetic engineering that are expected to accelerate the discovery and exploitation of γ-amino acid-containing natural products.

Covering: 2021 to 2026Methyltransferases (MTs) using S-adenosyl-L-methionine (SAM) and its analogs enable highly selective alkylation reactions. Until lately, broader application was limited by the inefficiency of SAM regeneration and laborious synthesis of SAM analogs. Recent advances in enzymatic in situ supply and regeneration overcome these barriers, facilitating progress toward in vivo alkylation, advanced MT-based labeling in cells as well as application in preparative synthesis. We summarize advances in one-step regeneration, biomimetic multi-enzyme pathways, and engineered whole-cell systems that (re)generate SAM analogs from methionine analogs, alkanethiols, haloalkanes and related alkylation reagents, covering the period from 2021 to 2026. Cofactor modifications include variations at the methyl unit, amino acid moiety, and nucleobase to expand scope, enhance stability and offer orthogonality in complex reaction mixtures. Together, these advances extend transferase chemistry beyond methylation, opening new avenues in biocatalysis, drug discovery, synthetic-method development, and synthetic biology.

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

Covering: up to July 2026The vinylogous Mannich reaction (VMR) enables γ-selective carbon-carbon bond formation between vinylogous nucleophiles and imines or iminium ions, yielding δ-aminocarbonyl frameworks. Compared with the classical Mannich reaction, VMR shows distinct advantages in remote functionalization and convergent bond formation, facilitating the rapid assembly of nitrogen-containing heterocycles, multiple stereogenic centers, and densely functionalized intermediates. As a result, this reaction has become an increasingly valuable strategy for generating complexity in the total synthesis of alkaloids and has been successfully applied to a wide range of alkaloid families, including piperidine, pyrrolidine, indole, Securinega, Stemona, phthalideisoquinoline, steroidal, and Daphniphyllum. This review presents a structured and concept-oriented overview of VMR-based alkaloid synthesis. Representative applications are organized according to the nature of the vinylogous nucleophiles, including both acyclic and cyclic dienol equivalents. Particular emphasis is placed on reaction design, stereochemical control, complexity generation, and the integration of VMR into asymmetric, collective, and biomimetic synthetic strategies. Overall, this review highlights the evolution of VMR from a methodological variant of the classical Mannich reaction into a broadly applicable approach for the efficient synthesis of structurally diverse alkaloids. It also provides perspectives on its future development in alkaloid synthesis.

Focuses on the period 2020-2025Antibiotics remain a cornerstone of modern medicine, with natural products representing many of the molecules used in the clinic or in agriculture. Nonribosomal peptides represent a significant class within our antibiotic arsenal, with the tantalising prospects for engineering the megaenzyme machineries that produce these molecules continuing to captivate the fields of enzymology, biocatalysis and discovery. Recent studies have demonstrated that there is significant diversity yet to be elucidated within both the types of molecules produced by these assembly lines and the enzymatic machineries that produce them, and thus the field of antibiotics produced by NRPS biosynthesis will continue to grow. This review seeks to highlight the impressive nature of recent discoveries made by the field over the period from 2020-2025, including the identification of novel antimicrobial peptides produced by NRPS assembly lines, exemplars of novel substrates and transformations within the assembly of these peptides, the role of chemistry in supporting both the discovery and engineering of these pathways, and key discoveries that challenge established paradigms within the field in terms of how nature can assemble bioactive antimicrobial peptides.

Covering: 2019 to April 2026Bile acids, originally identified as digestive emulsifiers, are now recognized as signaling molecules at the nexus of metabolism and immunity. Recent advances in metabolomics have revealed unexpected chemical diversity of BAs, derived from previously unrecognized conjugation pathways involving both the gut microbiota and the host. This includes microbial conjugation of the bile acid carboxy terminus with diverse amino acids and other biogenic amines as well as host-derived conjugation with cysteamine derivatives. In addition, microbial acylation of the steroid core has been shown to introduce succinyl, acetyl, and other chemical modifications, including expansion of the canonical bile acid carbon skeleton. This review synthesizes recent discoveries (2019-2026) in bile acid conjugation chemistry and highlights how the expanded bile acid diversity regulates host physiology through activation of different nuclear receptors and G-protein coupled receptors, including therapeutic implications for metabolic and immune disorders such as non-alcoholic steatohepatitis, inflammatory bowel disease, and cardiometabolic diseases. The emerging picture reveals that bile acid pools result from an intricate network of host-microbe metabolic pathways, and that considering both host and microbial contributions is essential for understanding bile acid biology in health and disease.

Covering: up to the end of April 2026Chimeric natural products are formed when biosynthetic inputs from distinct pathways, gene clusters, or metabolic branches are integrated into a single scaffold. In bacteria, such crosstalk-driven assembly can generate structurally diverse metabolites with distinct biological activities. However, these metabolites remain underexplored because most discovery pipelines are optimized to connect one metabolite family to one co-localized biosynthetic gene cluster (BGC). As a result, metabolites produced through inter-pathway collaboration, recruitment of primary-metabolic intermediates, or non-enzymatic coupling of products from separate pathways are often deprioritized as genome-metabolome mismatches. Here, we describe chimeric natural products as an important yet overlooked class of bacterial metabolites and present a discovery framework that prioritizes candidate hybrid scaffolds from LC-MS-based metabolomics. We suggest that public-repository spectral searching, multi-class MS/MS annotation, retrospective genome-to-metabolite linkage, and isotope-guided validation can improve discovery of these overlooked scaffolds. Prioritizing such metabolites can expand natural product discovery beyond canonical frameworks, uncover new biosynthetic design principles, and inform future efforts to engineer hybrid molecules.

Covering: 1944-2025Nature's biosynthetic repertoire extends far beyond conventional CHON(S) chemistry and encompasses a rare but diverse array of natural products that incorporate atypical elements such as arsenic, selenium, fluorine, iodine, boron, and vanadium. These metabolites reveal how living systems have evolved to harness atypical atoms through both enzyme-mediated and spontaneous chemical strategies. Biological C-F and Se-C bond formation, SAM-dependent arsenic methylation, and non-enzymatic boron complexation exemplify nature's ingenuity in overcoming extreme energetic or coordination constraints. Despite their scarcity, these compounds play critical ecological and physiological roles in detoxification and redox regulation (As, Se), defense, and signaling (F, I, B), and in some cases, sustain global biogeochemical cycles (Mo, V). Structurally, they exhibit exceptional chemical stability, redox versatility, and metal-ligand diversity. Functionally, these findings expand our understanding of enzyme evolution, chemical defense strategies, and symbiotic metabolism in both marine and terrestrial ecosystems. Recent genomic and biochemical advances have uncovered new families of atypical natural products and the specialized enzymes responsible for their formation. Taken together, these discoveries define the limits of biogenic chemistry and highlight promising avenues for sustainable biocatalysis and drug discovery, particularly in the fluorination, selenation, and boronation pathways that bridge biological and synthetic chemistry.

Covering: up to 2026Strigolactones dominate the research on parasitic plant germination. Nevertheless, other types of natural products have roles in stimulating or inhibiting the germination and subsequent growth of parasitic weeds, including synergistic interactions with other compounds released by host roots that mediate host recognition and chemotropism. This review focuses on the bioactive non-strigolactone compounds, classified as terpenes and terpenoids, aromatic metabolites, N-containing metabolites and miscellaneous structures. Terpenes and terpenoids are the most common germination stimulants (51.0% of the total, among which sesquiterpene lactones represent the most common structures), while aromatic (41.7%) and N-containing (36.5%) metabolites are the leading inhibitors of germination or seedling development. The clog P trends suggest that molecular lipophilicity alone does not allow distinguishing between stimulants or inhibitors, but the data showed that two main intervals are particularly enriched in bioactive structures: moderately lipophilic compounds (47%, with clog P values between 1.0 and 3.0) and hydrophilic molecules (24%, with clog P below 0). An evaluation of germination-induced specificity indicated that sesquiterpene lactones are the strongest elicitors for O. cumana, P. aegyptiaca and S. asiatica, karrikin₁ and different terpenoids for O. minor and S. hermonthica, and isothiocyanates for P. ramosa. Notably, several sesquiterpene lactones and isothiocyanates induced germination at concentrations comparable to those of natural strigolactones. Beyond germination, recent findings implicate non-strigolactone cues in haustorium initiation and host chemotropism, underscoring the complexity of chemical signaling in parasitic plant development. Overall, the evidence gathered herein shows that parasitic development is influenced by a wider chemical space than strigolactones alone, opening perspectives for eco-rational bioherbicide development and for understanding host-parasite communication.

Covering: up to the end of 2025.Plant specialized metabolites shape plant color, aroma, and stress adaptation while providing high-value natural products. Although transcription factors have long been regarded as central regulators of specialized-metabolite biosynthesis, increasing evidence indicates that chromatin-associated epigenetic regulatory mechanisms provide additional layers of control over transcriptional responsiveness, chromatin accessibility, and metabolic output. Here, we briefly discuss how distinct epigenetic regulatory mechanisms, including DNA methylation, chromatin remodeling, histone methylation, and histone acetylation, contribute to plant specialized metabolism through different regulatory principles. Among these mechanisms, histone acetylation/deacetylation appears particularly important for rapidly reversible and environmentally responsive transcriptional regulation. Using anthocyanin biosynthesis as the most mechanistically resolved paradigm, we highlight how dynamic histone acetylation integrates environmental and phytohormonal cues with transcriptional networks to fine-tune metabolic gene expression. This framework provides new insights into chromatin-mediated metabolic regulation and offers opportunities for achieving precise, predictable, and durable metabolic engineering in plants.