(118e) Computation-Driven Analysis of Model Polyextremotolerant Fungus Exophiala Dermatitidis: Defensive Pigment Metabolic Costs and Human Applications

The polyextremotolerant black yeast Exophiala dermatitidis is a tractable model system for investigation of adaptations that support growth under a variety extreme conditions such as pH, light, radiation, anti-fungal compounds, temperature, and more. Foremost amongst these adaptations is melanogenesis and carotenogensis, which produce the two primary defensive pigment classes in E. dermatitidis: melanins and carotenoids. A particularly important question is their metabolic production cost, which can give insight into the costs and trade-offs associated with and limits to polyextremotolerance. However, investigation of this issue has been hindered by a relatively poor systems-level understanding of the E. dermatitidis genome and metabolism. To address this challenge, a genome-scale model (iEde2091) was developed using a variety of tools to overcome current knowledge gaps such as BLASTp and OptFill. By applying the concept of shadow price to the production of pigments in iEde2091, carotenoids were found to be more expensive to produce than melanins. Given that all functions performed by carotenoids are also known to be performed by melanins and that melanins are the first line of defense, this suggests that carotenoids have an underexplored yet important role, possibly in photo-protection. Furthermore, given that defensive pigments with overlapping functions generally have different shadow prices under different growth conditions, this might indicate that E. dermatitidis may minimize the cost of polyextremotolerance through selective production of the least expensive pigment. In addition to shadow price analyses, 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.

Publication: W. L. Schroeder, S. D. Harris, and R. Saha. “Computation-driven analysis of model polyextremotolerant fungus Exophiala dermatitidis: defensive pigment metabolic costs and human applications”. iScience, vol. 23, no. 4, Apr. 24, 2020. Available: https://www.cell.com/iscience/fulltext/S2589-0042(20)30164-4 (doi: https://doi.org/10.1016/j.isci/2020.100980)