Hui Li, Yu-Yen Yang, Santosh Chokkakula, Kuppusamy Sathishkumar, Mohammed Mujahid Alam, Abdullah G. Al-Sehemi, Xi Zhang, Siomui Chong, Gnanaprakash Jeyaraj
Fungi play a dual role as indispensable ecological engineers and as major agents of disease in humans, animals, and plants. Recent estimates highlight their substantial impact, with millions of invasive infections annually and severe agricultural losses threatening food security. At the same time, fungi underpin ecosystem services such as decomposition, soil aggregation, and carbon sequestration, while also serving as prolific sources of enzymes, metabolites, and sustainable biomaterials. Advances in single-cell and spatial omics, cryo-electron microscopy, AlphaFold-based structural predictions, and machine learning applied to biosynthetic gene clusters are transforming the study of fungal pathogenicity, symbiosis, and metabolism. These approaches are shifting fungal research from descriptive biology toward predictive, translational pipelines that connect mechanistic insights to drug discovery, resistance management, and biotechnological innovation. Nevertheless, challenges remain, including antifungal resistance, climate-driven emergence of new pathogens, limited therapeutic options, and bottlenecks in scaling fungal applications for sustainability. Addressing these requires integrated One Health strategies that bridge clinical, agricultural, and environmental perspectives. By uniting structural biology, omics, genome editing, and computational tools within a global framework, fungal biology can be harnessed not only to mitigate emerging risks but also to drive innovations in medicine, agriculture, and green technologies.