Computation-Driven Mechanistic Understanding of the Cellular Cost and Role of Defensive Pigment Production in a Polyextremotolerant Fungus

The polyextremotolerant black yeast Exophiala dermatitidis is a tractable model system for investigation of adaptations under extreme conditions. Foremost amongst these adaptations is production of the defensive pigments melanins and carotenoids. A particularly important question is their metabolic production cost. However, this investigation has been hindered by a relatively poor systems-level understanding of E. dermatitidis metabolism. To address this challenge, a genome-scale model (iEde2091) was developed. Using iEde2091, 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 of photo-protection under high-energy visible light. Furthermore, multiple defensive pigments with overlapping functions might allow E. dermatitidis to minimize cost. Because iEde2091 revealed that E. dermatitidis synthesizes 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.