Glutamate dehydrogenases in fungi: From biology to biotechnology

Glutamate dehydrogenases (GDH; EC 1.4.1.2 and EC 1.4.1.4) play a pivotal role in fungal nitrogen metabolism by catalyzing the reversible conversion of 2-ketoglutarate to L-glutamate. In fungi, NAD- as well as NADP-dependent GDHs function at the interface of ammonia assimilation and glutamate catabolism, contributing to growth, differentiation, and morphogenesis. The evolution of fungi to adapt and occupy various ecological niches is closely aligned to the diversity of regulations of the functions of GDHs, their localisation and biochemical characteristics. This review explores the biochemical, molecular, and structural studies on fungal GDHs, emphasizing their catalytic diversity, coenzyme specificity, and regulatory mechanisms, including phosphorylation, thiol modulation, and allosteric control. Structural elucidations of NADP-GDHs from Aspergillus niger, Aspergillus terreus, and Candida albicans provide new insights into cofactor binding, substrate recognition, and inhibitor interactions. Molecular analyses reveal distinct evolutionary trajectories for NAD- and NADP-GDHs across fungal taxa, with GDH-mediated transitions linked to morphogenetic processes such as the yeast-to-hypha (Y-H) switch, highlighting GDHs as promising antifungal drug targets. The comprehensive survey of fungal GDHs presented here emphasises their biochemical versatility, evolutionary significance, and translational potential in agriculture, biosensor development and in industry. The review also highlights gaps in our understanding of fungal GDHs and potential areas for further research.