A Broad-Spectrum Copper Oxidase Synthesizes Fungal Peptidomelanin

Peptidomelanin is a fungal biopolymer secreted during the germination of Aspergillus niger melanoliber spores. Peptidomelanin is composed of an insoluble core polymer derived from L-DOPA, surrounded and solubilized by short, heterogeneous peptide chains. In this work, we report the identification and biochemical characterization of BroSCO (gene ID: ABHI18_005222), a broad spectrum copper oxidase responsible for synthesizing peptidomelanin. Our model of BroSCO possesses a type 3 dicopper center housed in a large, solvent accessible catalytic center that can accommodate substrates possessing a range of sizes. BroSCO polymerizes L-DOPA into melanin along the Raper-Mason pathway. BroSCO oxidizes thiol groups from cysteine and cysteinylated peptides, allowing them to copolymerize with L-DOPA, forming peptidomelanin in the latter case. Our identification of BroSCO as the enzyme responsible for synthesizing peptidomelanin lead to the characterization of a previously unknown biochemical pathway, expanding our understanding of fungal biochemistry and melanogenesis.