Natural Product Reports最新文献

Correction for ‘Unpacking policy developments in marine natural product research: a scientist's guide to DSI and BBNJ’ by Federica Casolari et al., Nat. Prod. Rep., 2025, 42, 1063–1070, https://doi.org/10.1039/D4NP00070F.

Covering: up to 2025

Metallophores are metal-chelating natural products produced by microorganisms to scavenge essential metal ions in nutrient-limited environments. Among them, yersiniabactin-type metallophores (YTMs) represent a structurally and functionally distinct subgroup with a growing role in host–microbe and microbe–microbe interactions. In contrast to flexible hydroxamate- and carboxylate-type siderophores, YTMs feature a linear, pre-organized arrangement of aryl and five-membered heterocycles, often derived from modular nonribosomal peptide synthetase (NRPS) pathways in combination with polyketide synthase (PKS) domains. Their biosynthesis is encoded by gene clusters that integrate precursor formation, assembly line machinery, and metal transport components. Salicylic acid-derived aryl units and cysteine/serine-derived heterocycles are tailored through oxidation, methylation, and glycosylation, giving rise to complex chelators with a broad metal-binding profile—including Cu(II), Co(II), Ni(II), and Zn(II)—but weaker Fe(III) affinity. Due to structural ambiguity in current terminology, we propose a refined definition for YTMs based on specific connectivity of aryl and heterocyclic units and demonstrated metal chelation. We distinguish YTMs from simpler aryl-hetaryl siderophores such as anguibactin and pre-acinetobactin, and argue against broader umbrella terms like “mixed” or “salicyl-capped” siderophores. This review provides a comprehensive overview of the structural, biosynthetic, and genomic features of YTMs and introduces a classification framework based on a comprehensive biosynthetic pathway survey to facilitate the comparisons across natural product families. Given their prevalence in pathogens prioritized by the World Health Organization, including Pseudomonas aeruginosa and Mycobacterium tuberculosis, YTMs represent promising targets for both ecological and therapeutic exploration.

Covering: 2021 to 2025Microbial communities represent a vast and largely untapped source of natural products with potential applications in various fields, including medicine, agriculture, and the biomanufacturing industry. Secondary metabolites play a crucial role in mediating interspecies interactions within these communities, influencing their structure and function. Recent advances in microbial genetic engineering and multi-omics technologies have enabled the harnessing of these interactions for enhanced natural product discovery and production. These techniques, coupled with systems biology and mathematical modelling, allow for the rational design and manipulation of microbial consortia to elicit the expression of cryptic biosynthetic gene clusters and to optimize the production of desired compounds. Additionally, direct mining of microbiomes using metagenomics, metatranscriptomics, and metabolomics has revealed a wealth of novel biosynthetic gene clusters and secondary metabolites with potential therapeutic and industrial value. Despite the challenges associated with cultivating and characterizing diverse microbial species, ongoing advancements in computational tools and data analysis are rapidly expanding our ability to explore and exploit the seemingly inexhaustible reservoir of natural products hidden within microbial communities.

Covering: up to 2025This review explores the potential of bioinformatics and chemoinformatics tools to advance the exploration of natural extracts libraries (NELs). Although metabolomics has become a term used routinely in natural product (NP) research, the field remains focused on individual molecules or small sets of compounds, which restricts scalability. This narrow focus is mirrored in the computational handling of generated data, limiting broader insights. By challenging the traditional molecule-first paradigm-a framework historically shaped by practical constraints-we present our vision of using computational approaches to unlock the full potential of NELs, now and in the future.

Covering 2010 to 2025

Sponges are benthic, sessile invertebrate metazoans that are some of the most prolific sources of natural products in the marine environment. Sponge-derived natural products are often endowed with favorable pharmaceutical bioactivities, and paired with their structural complexity, have long served as title compounds for chemical syntheses. Sponges are holobionts, in that the sponge host is associated with symbiotic and commensal microbiome. Natural products isolated from sponges can be produced by the sponge host, or the associated microbiome. Recent genomic studies have shed light on the sponge eukaryotic host as the true producer of several classes of sponge-derived peptidic natural products. In this review spanning years 2010–2025, we describe peptidic natural products isolated from the sponge hosts and the associated microbiome, detail their biosynthetic processes where known, and offer forward looking insights into future innovation in discovery and biosynthesis of peptidic natural products from marine sponges.

Covering: up to April 2025

Bacterial aromatic polyketides represent a notable class of natural products that have found extensive applications in clinical treatments. In their biosynthesis, oxidative rearrangements represent critical transformations that typically afford diverse scaffolds, structural rigidity, and biological activities. In this context, it is evident that redox enzymes are frequently implicated in various rearrangement processes, whereby they facilitate the transformation of pathway precursors into mature natural products. In this review, we will elucidate how natural enzymes utilize redox chemistry to create new carbon skeletons in the field of bacterial aromatic polyketide biosynthesis. Representative unique examples of Baeyer–Villiger and Favorskii-type oxidative rearrangements catalyzed by flavin-dependent monooxygenases, innovative carbon skeleton rearrangements catalyzed by ketoreductases and dioxygenases, as well as intermolecular dimerization catalyzed by CYP450s or NmrA-like proteins, are summarized and discussed. Concurrently, the structural characteristics and catalytic mechanisms of selected enzymes will also be introduced. By revealing the intriguing chemistry and enzymology behind these oxidative rearrangement transformations, this comprehensive review will not only enhance our comprehension of this uncommon chemical regularity but also provide potent biocatalysts for the semi-synthesis or synthetic biology of complex natural molecules.

Covering upto 2025

Rotenoids are angular hybrid isoflavonoids mainly characterized by an additional six-membered ring between the B and C rings of flavonoids. The extra ring introduces further chemical diversity to the densely substituted precursors, isoflavonoids, making rotenoids a significant group of compounds within the plant kingdom. Early biosynthesis studies by L. Crombie, Nat. Prod. Rep., 1984, 1, 3–19, and subsequent revisions housed rotenoids into three groups, based on the oxygenation pattern of the bridge carbons between rings B and C. Since then, many more new structures of rotenoids have been discovered, prompting a need to revisit this classification as key structural traits of rotenoids might contribute to phylogenetic relationships and lineage diversification of plants. The new classification builds upon previous considerations, but also incorporates the defining feature of rotenoids, the additional carbon at the C-6 position, leading to nine distinct classes (Types I–IX). Types I and VII were found with the most representatives, predominantly distributed across the Pentapetalae clade, but also found in a few monocots. Rotenoids were found in phylogenetically distant lineages within the clade, raising intriguing questions about the evolutionary pathways that led to their biosynthesis and how their occurrences could inform plant taxonomy. The review addresses these questions and provides a thorough understanding of rotenoids and their chemotaxonomy significance.

Focus on 2004 to 2024The rediscovery of natural products (NPs) as a critical source of new therapeutics has been greatly advanced by the development of heterologous expression platforms for biosynthetic gene clusters (BGCs). Among these, Streptomyces species have emerged as the most widely used and versatile chassis for expressing complex BGCs from diverse microbial origins. In this review, we provide a comprehensive analysis of over 450 peer-reviewed studies published between 2004 and 2024 that describe the heterologous expression of BGCs in Streptomyces hosts. We present a data-driven overview of expression trends across time, BGC types, donor species, and host strain preferences, offering the first quantitative perspective on how this field has evolved over two decades. Our review discusses the key factors influencing successful BGC expression in Streptomyces, including genomic integration strategies, regulatory elements, codon optimization, and precursor supply. We also examine the impact of synthetic biology tools, genome engineering, and host strain tailoring in overcoming common expression barriers. Special emphasis is placed on the role of heterologous expression in accessing silent or cryptic BGCs, elucidating biosynthetic pathways, and generating new-to-nature analogues through combinatorial biosynthesis. By integrating technological advances with practical case studies, we highlight how Streptomyces-based heterologous expression is enabling not only the efficient production of known compounds but also the discovery of structurally novel and biologically potent metabolites. This review aims to serve as a resource for researchers in natural products, synthetic biology, and drug discovery who seek to harness the full potential of microbial biosynthetic diversity.

Covering: 2000 to 2025

The Lamiaceae family, the sixth largest among angiosperms, is renowned for its rich diversity of terpenoids, many of which exhibit remarkable bioactivities, including anti-inflammatory, psychoactive, anti-cancer, and antiviral effects. Notable examples with fully elucidated biosynthetic pathways include menthol from peppermint, forskolin from blue spur flower, and carnosol from rosemary. For other key Lamiaceae terpenes—such as the anti-cancer oridonin, the psychoactive salvinorin A, and bioactive marrubiin and vitexilactone—significant progress has been made. This review explores the bioactivity and biosynthesis of Lamiaceae terpenes, with a focus on mono- and diterpenes, while highlighting future research directions.

Covering: 1942–2025

Bacteriophages (phages) are obligate viruses that infect bacteria. The antibacterial effects of both phages and natural products shape microbial ecosystems and have yielded competing antibiotic strategies. Phages have also intersected many times with natural products research throughout the past century. To discover antiviral leads, natural products were screened for anti-phage activity. To discover new anti-cancer drugs, natural products were screened for the ability to trigger lysis by the λ prophage—indicating DNA damage. Now, the antibiotic resistance crisis motivates the study of natural products that can synergize with phages to improve antibacterial therapies. Beyond applications, these parallel natural “chemical” and “biological” antibacterial factors combine to shape microbial communities across our planet. Here, we provide a comprehensive overview of natural products that modulate phage activities. We discuss their mechanisms of action, and we present opportunities for future research.