Integrated Enzymatic, Transcriptomic, and Metabolite Identification Insights into the Degradation of Diverse Endocrine-Disrupting Compounds by Pleurotus ostreatus GEMB-PO1

Endocrine-disrupting compounds (EDCs) represent a significant class of micropollutants that persist in environments and threaten ecological and human health. In this study, Pleurotus ostreatus GEMB-PO1 was investigated for its ability to degrade eight representative EDCs—bisphenol A (BPA), bisphenol F (BPF), tetrabromobisphenol A (TBBPA), butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), 17β-estradiol (E2), and estrone (E1). Enzymatic activity assays and inhibitor experiments confirmed the synergistic roles of CYP450s and laccases in mediating intracellular and extracellular transformation processes. Transcriptomic analysis revealed that EDC exposure triggered the activation of a coordinated gene network involving CYP450s, laccases, NAD(P)H-dependent dehydrogenases, and secondary metabolite biosynthesis pathways, suggesting a fungal-wide metabolic reprogramming to cope with oxidative and xenobiotic stress. LC-MS identified compound-specific intermediate metabolites and enabled the reconstruction of stepwise degradation pathways. While distinct degradation pathways were observed among different compounds, most converged on oxidative transformations, accompanied by dealkylation or hydrolysis depending on molecular structure. To our knowledge, this is the first study to integrate enzymatic, transcriptomic, and metabolite-level evidence to systematically resolve the degradation mechanisms of structurally diverse EDCs by a single fungal strain. These findings expand the mechanistic understanding of fungal EDC degradation and highlight the bioremediation potential of P. ostreatus GEMB-PO1.