Pan-Genome-Scale Metabolic Reconstruction Reveals Conserved Metabolic Functions in Candida albicans

Candida albicans is a major cause of human mucosal and invasive fungal infections, but the relationship between its intraspecific genomic diversity and metabolic variation remains poorly understood. Here, we integrated 80 public C. albicans genome assemblies, published fungal genome-scale metabolic models (GEMs), public reaction databases, and orthogroup-linked gene–protein–reaction (GPR) evidence to construct a species-level C. albicans pan-GEM and derived 80 strain-specific GEMs (ssGEMs) through genome projection. The pan-genome comprised 10,308 orthogroups, including 4215 core, 5947 accessory, and 146 singleton orthogroups. The final pan-GEM contained 1986 reactions, 1777 metabolites, and 865 genes. After feasibility rescue, all 80 ssGEMs met the feasibility criterion for predicted growth and passed the closed-uptake energy-generating-cycle test. Among experimentally essential genes with resolvable GPR associations, 23 were consistently predicted as model-essential across all final ssGEMs. As an application of the ssGEM collection, nutrient-boundary simulations showed that increasing D-glucose uptake markedly increased predicted growth across 79 feasible ssGEMs. This framework provides a reusable resource for comparing conserved metabolic functions and genome-projected reaction differences across C. albicans strains.