show Abstracthide AbstractCopper-azole based formulations were widely used against fungal decay for preservation of wood timbers. While efficient for wood protection, leaching of both copper and azole within the environment has deleterious impact on soils and surface waters. Moreover, no recycling process is currently available for these wood waste. By taking advantage of the fact that certain fungi have the capacity to cope with these active compounds, we propose that some ligninolytic fungi could be good biocatalysts for detoxifying copper-azole formulations. Using the white-rot fungus Phanerochaete chrysosporium as a model, we demonstrated that the main strategies implemented by this fungus to counteract the antifungal effect of the product, in particular azoles, are the modulation of the lipids and sterols content, the maintenance of DNA integrity, detoxification of azoles by extracellular degradation likely through the Fenton chemistry, biosorption at the cell wall, efflux, and intracellular detoxification by the three-step detoxification pathway. By using comparative transcriptomics between a copper-azole formulation and a copper-quaternary ammonium formulation, we manage to identify genes specifically involved in azole resistance and detoxification within this complex system, opening perspectives for both the identification of key molecular players that could be the targets for developing long-term acquired antifungal resistance mechanisms, and the management of azoles residues by mycoremediation processes. Overall design: Phanerochaete chrysosporium RP78 was cultivated with or without Tanalith E3474 and Korasit KS2. Fungal mycelium was harvested post 3 days fungal growth. Libraries from total RNA (PolyA) were constructed and 2 × 150 bp Illumina NovaSeq6000 sequencing (RNA-Seq) was performed.Three biological replicates from each treatment were generated.