The Underexplored Genus Microbispora: A Treasure Trove of Secondary Metabolites with Diverse Chemistry, Potent Bioactivities, and Biosynthetic Insights

Marine-Derived Rare Actinomycetes: Metabolites and Their Biosynthesis

Marine-derived rare actinomycetes are a chemically prolific yet underexploited source of structurally diverse secondary metabolites. In this review, rare actinomycetes are operationally defined as marine-derived non-Streptomyces actinomycetes that remain comparatively underexplored yet possess demonstrated or predicted capacity for specialized-metabolite biosynthesis. Genome sequencing has revealed that their biosynthetic potential greatly exceeds the range of metabolites recovered under standard cultivation conditions. However, many reported compounds remain only loosely associated with the gene clusters that encode them. This review provides a biosynthesis-centered perspective on marine-derived rare actinomycetes, focusing on secondary metabolites for which biosynthetic gene clusters (BGCs) or pathways have been proposed, experimentally assessed, or functionally validated. It focuses on compounds reported after 2017, along with earlier metabolites whose biosynthetic origins were resolved only later. Representative examples are organized by genus and structural class and weighed according to the level of evidence linking each metabolite to its BGC, ranging from bioinformatic prediction and metabolomic correlation to validation by gene inactivation, heterologous expression, and enzymatic characterization. The surveyed metabolites include polyketides, nonribosomal peptides, polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids, siderophores, angucyclines, anthracyclines, macrolides, diketopiperazine derivatives, and other unusual scaffolds. Collectively, these findings indicate how integrating genome mining, metabolomics, and molecular networking with targeted biosynthetic experiments can accelerate marine natural product discovery and unravel novel enzymatic functions and biosynthetic mechanisms in rare actinomycetes.

Biosynthetic Diversity of Marine-Derived Streptomyces Natural Products: Integrating Genome Mining, Multi-Omics, and Translational Drug Discovery Strategies

Marine-derived Streptomyces are among the most prolific producers of structurally diverse and biologically active natural products. Adaptation to unique marine environments, including deep-sea sediments, hydrothermal vents, mangrove ecosystems, marine invertebrates, and hypersaline habitats, has promoted the evolution of specialized biosynthetic systems capable of generating a broad spectrum of secondary metabolites. These metabolites include polyketides, non-ribosomal peptides (NRPs), ribosomally synthesized and post-translationally modified peptides (RiPPs), terpenoids, alkaloids, and hybrid compounds with significant antibacterial, antifungal, antiviral, antiparasitic, anti-inflammatory, and anticancer activities. Recent advances in genome sequencing, bioinformatics, genome mining, metabolomics, synthetic biology, and artificial intelligence (AI)-assisted discovery have substantially expanded marine natural product research by enabling the identification and prioritization of previously inaccessible biosynthetic gene clusters (BGCs). However, major challenges remain, including silent biosynthetic pathways, low cultivation efficiency, rediscovery of known compounds, metabolite yield instability, dereplication bottlenecks, and limited ecological interpretation. These constraints continue to impede the translation of biosynthetic potential into pharmaceutical applications. This review summarizes current strategies for marine natural product discovery and highlights emerging translational approaches integrating multi-omics technologies, pathway engineering, and AI-guided prioritization. Collectively, these advances provide a roadmap for advancing marine Streptomyces research from descriptive omics-based exploration toward experimentally validated and clinically relevant drug discovery.

Aspergillus-derived indole diketopiperazines (IDKPs): chemical diversity, biosynthetic logics, and therapeutic potential.

This review emphasizes the unique capacity of Aspergillus species to generate structurally diverse IDKPs and highlights the potential of genome mining and biosynthetic gene cluster (BGC) analysis for uncovering previously unexplored IDKP biosynthetic pathways.

Unveiling the diversity, bioactive metabolites and therapeutic potential of endophytic fungi of the Apocynaceae family: a comprehensive review

Endophytic Fungi Natural Factories of Novel Bioactive Compounds

ABSTRACT Endophytic fungi represent a prolific and chemically diverse source of novel specialized metabolites with significant pharmacological potential. This systematic review examines 118 studies published between 2024 and 2025, reporting the discovery of 242 previously uncharacterized bioactive compounds. These metabolites belong to several major chemical classes, including peptides (4), terpenoids and steroids (58), alkaloids and other nitrogen‐containing compounds (51), polyketides (85), lactones (22), ketones (5), chromone compounds (3), and others (9). The genera Aspergillus (28), Penicillium (21), Diaporthe (7), Talaromyces (10), and Trichoderma (6) were identified as the most productive sources. The investigated endophytic fungi were isolated from a wide range of plant hosts and ecological niches, reflecting the extensive biodiversity of endophytic communities. Biological screening demonstrated that a substantial proportion of the tested compounds exhibited diverse bioactivities, including anti‐inflammatory, antibacterial, antifungal, antimicroalgal, and cytotoxic effects. Collectively, the remarkable structural diversity and broad biological profiles of metabolites derived from endophytic fungi highlight their strong potential as promising lead scaffolds for future pharmaceutical development.

Lichen metabolites as potential natural products: a review

Lichens, a unique and complex symbiotic association between fungi and photosynthetic partners (algae and/or cyanobacteria), represent a largely underexplored source of bioactive compounds with significant pharmaceutical, nutraceutical, and industrial potential. They produce a diverse array of secondary metabolites such as usnic acid, atranorin, and vulpinic acid, showing antimicrobial, anticancer, antiviral, antioxidant, herbicidal, insecticidal, antipyretic, and anti-inflammatory activities. The structural uniqueness and chemical diversity of lichen derived metabolites, combined with their ecological divergent distribution make them an invaluable reservoir of natural products for commercial exploitation. In recent years, growing global demand for natural therapeutics, ecofriendly cosmetics, and sustainable agricultural products has intensified interest in lichen bioresources as an alternative. This review aims to provide a comprehensive overview of the major classes of lichen metabolites reported during the period from 1986 to 2026, with particular emphasis on their bioactivities, mechanisms of action, and current and potential future applications. Lichens might become “green gold” if contemporary biotechnological tools like microbial fermentation, metabolic engineering, and synthetic biology are combined with high throughput screening methods, green extraction strategies, and government backed entrepreneurial initiatives.