Zearalenone Biotransformation by Tibetan Plateau-Derived Yeast Hannaella zeae: Biological Pattern Elucidation, Metabolite Safety, and Environmental Tolerance

Zearalenone (ZEN) poses serious risks to human and animal health. Compared with physical and chemical methods, microbial transformation offers a safer and more sustainable strategy for ZEN detoxification. The yeast <i>Hannaella zeae</i>, isolated from the Qinghai-Tibet Plateau, showed the highest ZEN removal efficiency among 11 strains, achieving an 85.87% transformation rate within 36 h. Optimal conditions for ZEN transformation were determined by varying culture time, temperature, and pH. The products were putatively identified as zearalenone-14-β-D-glucopyranoside (C₂₄H₃₂O₁₀) and zearalenone-16-β-D-glucopyranoside (C₂₄H₃₂O₁₀) by UHPLC-Q-Orbitrap-HRMS. The safety of the mixed culture medium extract was further evaluated using a <i>Caenorhabditis elegans</i> model, showing significantly lower toxicity than untreated ZEN. <i>H. zeae</i> maintained high transformation efficiency under low temperature (57.48%) and acidic stress (47.10%), supported by active antioxidant enzymes (SOD, CAT, APX, GPx) and stress metabolites (trehalose, proline). Overall, this study identifies <i>H. zeae</i> as a promising, stress-tolerant biocontrol agent and elucidates its glycosylation-based detoxification mechanism, providing a foundation for future application in real food and feed systems.