Integrated multi-omics reveal the multidimensional mechanisms of Penicillium sp. in selenite biodegradation

Bioremediation is a green and efficient strategy for detoxifying toxic metalloids like selenite. However, the molecular mechanisms underlying microbially driven selenite transformation are still not fully understood. Here, an integrated transcriptomic and proteomic approach was employed to elucidate the molecular mechanisms of sodium selenite (Na₂SeO₃) reduction by Penicillium sp. strain PM2, which was isolated from a selenium-rich mine in Enshi City, China, shows high Se(IV) resistance, and was cultured under 0, 5 mM, or 10 mM Na₂SeO₃. Quantitative assays demonstrated effective Se(IV) removal and concurrent element selenium (Se⁰) formation. TEM, SEM and XPS confirmed the reduction of selenite to Se⁰. High-throughput RNA-Seq and TMT-based proteomics revealed 6175 differentially expressed genes and 695 differentially expressed proteins enriched in carbohydrate and amino acid metabolism, the tricarboxylic acid cycle, glutathione metabolism, redox processes, selenocompound/sulfur metabolism, and lipid remodeling. Key antioxidant enzymes, glutathione and thioredoxin systems, Fe-S cluster assembly proteins, oxidoreductases, and membrane transporters were significantly upregulated under Se(IV) stress. Four major metabolic modules-glutathione, thioredoxin, iron-sulfur cluster, and lipid metabolism-coordinated to maintain redox homeostasis, mitigate oxidative damage, and drive Se(IV) detoxification. While core redox responses are conserved across microbes, our multi-omics integration in a filamentous fungus reveals a dose-stratified deployment of fungal wall/lipid remodeling and transporter control that refines existing models. This study provides a mechanistic basis for the application of PM2 in selenium bioremediation and the green biosynthesis of Se nanoparticles (SeNPs).