Discovery and biosynthesis of antifungal microbial secondary metabolites

SUMMARYThe high mortality associated with invasive fungal infections, coupled with limited therapeutic options, underscores the urgent need for antifungal agents with novel mechanisms of action. Natural products represent a particularly valuable resource, providing structurally diverse and evolutionary refined scaffolds that often outperform those found in synthetic libraries. Historically, microorganisms have proven to be a rich source of antibiotics and other therapeutic agents. Access to diverse phylogenetic lineages and biosynthetic pathways has been essential for antifungal drug development. In this review, we highlight the chemical and biosynthetic diversity of antifungal natural products derived from both fungi and bacteria. We emphasize that microbial natural products continue to play a crucial role in antifungal development, particularly through the integration of natural product chemistry, microbiology, genetics, and advanced omics technologies.