摘要:SummaryThe polyextremotolerant black yeastExophiala dermatitidisis a tractable model system for investigation of adaptations that support growth under extreme conditions. Foremost among these adaptations are melanogenesis and carotenogenesis. A particularly important question is their metabolic production cost. However, investigation of this issue has been hindered by a relatively poor systems-level understanding ofE.dermatitidismetabolism. To address this challenge, a genome-scale model (iEde2091) was developed. UsingiEde2091, carotenoids were found to be more expensive to produce than melanins. Given their overlapping protective functions, this suggests that carotenoids have an underexplored yet important role in photo-protection. Furthermore, multiple defensive pigments with overlapping functions might allowE.dermatitidisto minimize cost. BecauseiEde2091 revealed thatE.dermatitidissynthesizes the same melanins as humans and the active sites of the key tyrosinase enzyme are highly conserved this model may enable a broader understanding of melanin production across kingdoms.Graphical AbstractDisplay OmittedHighlights•Exophiala dermatitidiscan be a model polyextremotolerant and melaninized organism•Its genome-scale model is reconstructed to study melanin and carotenoid metabolism•The shadow price analysis indicates a potential underexplored role of carotenoids•Comparisons between human andE. dermatitidismelanin synthesis are madeMicrobiology; Bioinformatics; Metabolic Engineering