Functional redundancy and divergence of UDP-glucose 4-epimerases in galactose metabolism and cell wall biosynthesis in Aspergillus nidulans

Galactose-containing polysaccharides in the cell walls of filamentous fungi are vital for hyphal formation, mycelial aggregation, and adhesion. Uridine diphosphate (UDP)-glucose 4-epimerase, an enzyme capable of reversibly converting UDP-glucose to UDP-galactose, plays a key role in galactose metabolism. This study investigates the functional specialization and overlapping roles of UDP-glucose 4-epimerases, UgeA and UgeB, in Aspergillus nidulans. Enzyme activity assays revealed that UgeA catalyzes the interconversion of UDP-glucose and UDP-galactose, while UgeB facilitates both UDP-glucose/UDP-galactose and UDP-N-acetylglucosamine/UDP-Nacetylgalactosamine interconversions. Both UgeA and UgeB successfully restored growth in a yeast gal10 disruptant, indicating their involvement in galactose metabolism in vivo. Additionally, the ugeB disruptant of A. nidulans exhibited growth retardation during galactose metabolism, a defect that was alleviated by complementation with ugeB or multiple-copy expression of ugeA. These findings elucidate the complex interplay between sugar metabolism and cell wall synthesis in filamentous fungi and offer insights for the development of novel antifungal therapies.