Copper-responsive <i>lcc3</i> gene confers laccase (LCC3) hyperproduction and oxidative stress resistance in the ligninolytic fungus <i>Dichomitus squalens</i>

In this study, by integrating transcriptomics, proteomics and functional genetics, we elucidated that Cu2+ specifically induces the expression of specific laccase genes to enhance laccase activity in D. squalens. lcc3 is the sole laccase gene that is massively and specifically induced by physiological Cu2+ concentrations. We further clarified the function of its encoded protein: LCC3 protein not only enhances extracellular laccase activity but also confers Cu2+ tolerance via ROS scavenging and Cu2+ chelation. These findings uncover a unique copper-responsive regulon and establish the lcc3 gene as a promising target for metabolic engineering aimed at high-yield laccase production and robust fungal performance under metal stress.