Natural Product Reports最新文献

Covering: up to 2025Cardiac glycosides (CGs), a class of metabolites found in nature, comprise sugar residues, unsaturated lactone rings, and steroidal cores. As renowned phytotoxins, they play vital roles in maintaining ecological balance. CGs have been widely used in the treatment of cardiovascular diseases such as heart failure and tachyarrhythmia for more than 200 years. Recent studies have revealed that CGs have numerous applications in various disease therapeutic areas, including anticancer, immunomodulatory, anti-inflammatory, antiviral, and neuroprotective effects. However, the medicinal resources of CGs are mainly reliant on natural plant and animal extracts, which not only limits their sustainable supply but also increases development costs. With the growing understanding of the pharmacological value of CGs and their increasing demand in the pharmaceutical industry, the sustainable supply of medicinal resources will become a bottleneck limiting their further development. Therefore, the artificial synthesis of target active ingredients, including chemical (semi)synthesis and biosynthesis, is becoming a hot topic among scholars worldwide. This paper presents the first systematic review of recent research advances in the structure, distribution, chemical ecology, biological activities, and artificial synthesis of CGs. Finally, we discuss the current challenges and urgent issues in this field, aiming to promote the widespread application of CGs in medicine through comprehensive pharmacological studies and exploration of synthesis techniques.

Covering: 2014/2015 up to 2025.The global rise of antimicrobial resistance imposes a strong demand to develop new antibacterial drugs, and microbes have been a prime source for their discovery. Albicidins and cystobactamids, isolated from xanthomonadaceae and myxococcaceae, respectively, span a novel class of oligoarylamide antibiotics with a unique chemical scaffold featured by para-aminobenzoic acid building blocks. Both compounds exhibit broad spectrum and potent activity against Gram-positive and Gram-negative pathogens through inhibiting DNA gyrase and topoisomerase IV. This article summarizes the insights gained on this class since its initial disclosure in 2014/2015 up to 2025. It discusses natural derivatives, their biosynthesis and chemical synthesis, the unique binding mode to DNA gyrase, and systematic medicinal chemistry programs with >700 analogs that led to resistance-breaking antibiotics with in vivo efficacy. The review illustrates the importance of natural product research to address the global need for new antibiotics.

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: 1948 to 2025Ryanodane diterpenes (RDs) are a unique class of plant-derived natural products characterized by their complex, polyoxygenated pentacyclic frameworks. They have been primarily identified in plants from the Salicaceae and Lauraceae families. In recent years, RDs have garnered significant interest due to their notable bioactivities, particularly their modulation of ryanodine receptors (RyRs) and their insecticidal properties. Since the initial isolation of ryanodine from the shrub Ryania speciosa Vahl in 1948, a total of 135 natural RDs across nine subtypes have been discovered. These compounds exhibit a range of biological activities, including insecticidal, cardiac activity, and immunomodulatory effects. However, the limited natural abundance of RDs has posed challenges for their comprehensive biological evaluation. Fascinated by their high affinity for RyRs and their intricate polycyclic structures, synthetic chemists have pursued the total synthesis of RDs since the 1990s, with notable progress in recent decades. Advances in synthetic methodology have enabled the successful construction of key RD scaffolds, facilitating further exploration of their biological potential. This review provides a comprehensive overview of RDs from 1948 to May of 2025, highlighting their significance in drug discovery and development. It also emphasizes the need for interdisciplinary collaboration to fully harness the therapeutic potential of these complex natural products.

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: January 2014-June 2025. Previous review: Natural Product Reports, 2014, 31, 1612Natural products (NPs) have long been foundational in medicine, from ancient herbal remedies to the discovery of transformative drugs like morphine and quinine. The mid-20th century marked a 'golden age' for antibiotic discovery from natural sources, which then expanded into other therapeutic areas. However, by the late 20th century, other technological advances had shifted NPs from being a central component of the discovery process to one of several options. This review explores the current role of NPs in pharmaceuticals by analysing NP-derived (NP-D) drugs approved since 2014 and clinical candidates in development as of the end of 2024. 58 NP-related drugs launched between January 2014 and June 2025 were identified, which included 45 NP and NP-D new chemical entities (NCEs) and 13 NP-antibody drug conjugates (NP-ADCs). Next, all 579 drugs-388 (67%) of which were NCEs and 191 (33%) were new biological entities (NBEs)-approved globally from 2014 to 2024 were analysed. In total, 56 (9.7%) of these 579 drugs were classified as NPs or NP-Ds using this review's NP definition: 44 NCEs (7.6% overall; 11.3% of NCEs) and 12 NP-ADCs (2.1% overall; 6.3% of NBEs). The number of new NP-D NCEs and NP-ADCs has fluctuated between 0 and 8 annually since 2014, with an average of five approvals per year. Next, 125 NP and NP-D compounds were identified that were undergoing clinical trials or in the registration phase at the end of December 2024. Thirty-three new pharmacophores not previously found in approved drugs are now in development; however, only one has been discovered in the past 15 years. This review highlights the enduring promise of NPs, despite their diminished role in drug discovery, and advocates for renewed emphasis on bioassay-guided isolation and mode of action studies to identify new drug leads.