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 L-DOPA-derived core polymer surrounded and solubilized by short, heterogenous 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 di-copper centre housed in a large, solvent accessible catalytic center that can accommodate substrates possessing a range of sizes. 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.