Evolutionary diversity of sphingolipid metabolism proteins in fungi

Fungi are adapted to survive across environments with fluctuating oxygen availability. Transition to terrestrial and parasitic lifestyles required remodeling of the cell membrane, including sphingolipid composition. Ceramides occupy a central position in sphingolipid metabolism, a topic of growing biotechnological interest due to the high lipid-producing capacity of fungi. However, current knowledge of fungal metabolism is largely derived from Dikarya. Here, we characterize the repertoire of proteins involved in sphingolipid metabolism across the fungal tree of life and trace the evolutionary history of selected proteins. We identify 59 protein subfamilies, over half of which are widely conserved, while the remaining exhibit lineage-specific duplications and losses, suggesting roles in adaptive processes. Protein diversity is higher in lineages associated with aerobic conditions compared to anaerobic, often parasitic or endosymbiotic groups. Flagellated and non-flagellated fungi also differ, particularly in ceramide synthesis and sphingomyelin-processing enzymes. The divergence times of key sphingolipid-metabolizing enzymes, such as acid sphingomyelin phosphodiesterase and UDP-glucuronosyltransferase, correspond to the period of fungal terrestrialization in non-flagellated fungi, except in Glomeromycota and Dikarya, where the divergence of acid sphingomyelin phosphodiesterase coincides with the evolutionary radiation of flowering plants. These findings show the diversification of sphingolipid metabolism, suggesting its role in adaptation and membrane specialization during fungal evolution.