Natural Product Reports最新文献

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.

Covering: 1950 to up to the end of 2024

Natural products containing polycyclic aromatic hydrocarbons (PAHs) feature at least two fused aromatic ring systems, conforming to Hückel's rule and representing an important class of secondary metabolites with a wide range of biological activities. Among them, the subtype of natural products containing tricyclic and greater than tricyclic systems has been neglected for a long time. This review summarizes the isolation, structural features, bioactivities, biosynthetic pathways, and chemical synthesis of this special subtype reported over the past decades. This review provides a current understanding of the tricyclic and hyper-PAHs represented by anthracene, phenanthrene, acenaphthalene, pyrene, fluoranthene, and tetraphene from organic, biosynthetic, and pharmacological perspectives.

Covering: up to 2025

Microbial interactions involve complex processes shaped by their ecological contexts. Herbivore animal dung denotes an interesting ecological niche for the study of interorganism communication and competition mediated by small molecules. Coprophilous organisms, which inhabit or are associated with animal dung, have developed resourceful defense mechanisms to survive in this competitive environment. Fungi, in particular, are renowned for their ability to produce biologically active secondary metabolites, a chemical arsenal that fosters successful colonization of the dung substrate. With recent advancements in OMICs technologies and our extensive knowledge of coprophilous fungi diversity, we can now delve into the biosynthetic machinery of these organisms and explore the opportunities they offer for discovering new antimicrobials and other beneficial natural products. This review explores the potential of coprophilous fungi in the context of the intricate microbial dynamics of this substrate, particularly the biosynthetic and chemical diversity that make this environment especially promising for natural product discovery. Notably, taxa spanning multiple families within the Sordariomycetes, Dothideomycetes, and Eurotiomycetes have been reported to thrive in dung, highlighting their potential as a reservoir of unique metabolic capabilities. Indeed, 198 secondary metabolites, derived from polyketide, amino acid derived, terpene, and hybrid pathways, have been reported from these fungi, underscoring the remarkable scope of their biosynthetic potential.

Covering: up to 2025

Microbial synthesis of glycosaminoglycans (GAGs) facilitates sustainable biomanufacturing using cost-effective carbon feedstocks. This transformative framework is driven by three core innovations: de novo GAGs biosynthesis, sulfation engineering, and new-to-nature GAGs analogs creation. Despite these advances, critical challenges hinder industrial-scale efficiency, such as suboptimal distribution of metabolic flux, insufficient sulfation environments, and host incompatibility with unnatural analogs. In this review, we present a systematic analysis of microbial hosts, biosynthetic pathways, and microbial engineering strategies for GAGs production. We first describe how strategic host optimization and pathway manipulation can tap the full potential of microorganisms for efficient GAGs biosynthesis. Then, we analyze the development of microbial cell factories (MCFs) for GAGs biosynthesis from the simple pathway transplantation to systemic de novo construction of metabolic systems, thereby establishing programmable platforms to surpass natural biosynthesis limits. Next, we present a tripartite engineering framework for GAGs sulfation that integrates precursor synthesis modules, sulfate donor accumulation systems, and sulfotransferase networks, thereby progressing sulfation control from biomimetic mechanisms to programmable artificial systems. Further, we discuss the microbial synthesis of new-to-nature GAGs analogs through the incorporation of unnatural precursors or the reprogramming of natural precursors, thereby enabling MCFs to construct non-canonical glycopolymers with designed function. Finally, we prospect the development of multifunctional customized MCFs to drive breakthroughs in industrial-scale GAGs bioproduction.