Natural Product Reports最新文献

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.

Covering: 2013 to 2024

Cycloaddition reactions, which efficiently construct polycyclic ring systems and stereocenters, are powerful tools in the total synthesis of natural products. Given the significant progress and numerous elegant applications of [5 + 2] cycloaddition reactions over the past decade, this review systematically summarizes the advances in three major types of [5 + 2] cycloaddition reactions in natural product synthesis from 2013 to 2024. The advantages of [5 + 2] cycloadditions in constructing complex natural product frameworks are illustrated through comparisons with alternative strategies for the same targets. Additionally, trends and future prospects for [5 + 2] cycloadditions are discussed, offering valuable insights for further research and broader applications.

Covering: up to 2025.Non-ribosomal peptide synthetases and polyketide synthases are modular biosynthetic systems that produce structurally diverse and pharmacologically potent natural products, including antibiotics, immunosuppressants, and anticancer agents. Their programmable architecture has long inspired efforts in biosynthetic re-engineering. This review highlights recent advances that are transforming non-ribosomal peptide synthetase and polyketide synthase systems into versatile platforms for rational design. We discuss progress in genome mining, high-throughput screening, and dereplication, alongside emerging tools from synthetic biology and computational modeling. Particular focus is given to structure-based approaches-such as homology modeling, molecular docking, and molecular dynamics simulations-as well as deep learning strategies for enzyme prediction and design. Rather than replacing classical techniques, these computational methods now complement and extend them, enabling accelerating the discovery and assembly of tailor-made natural product analogs.