A distinct zearalenone detoxification strategy mediated by cytochrome P450

Developing the bio-detoxification of estrogenic mycotoxin zearalenone (ZEN) and its more potent metabolite α-zearalenol (α-ZOL) represents a research priority in food safety. Here, we report a variant cytochrome P450 enzyme termed T8F3 that consumes 54% ZEN and 63.9% α-ZOL in an initial screening assay. The hydroxylated products of ZEN and α-ZOL, termed ZEN-P and ZOL-P, respectively, were isolated, purified and structurally characterized. The estrogenicity of ZEN-P and ZOL-P is suppressed by 21- and 105-fold, respectively, compared with their parental compounds. Structural elucidation shows that T8F3-catalyzed hydroxylation at β-C8' (ZEN) and α-C3' (α-ZOL) positions, which might introduce steric hinderance that compromises the binding to estrogen receptor α, establishing a structure-detoxification relationship. Altogether, our study reports the first P450-mediated hydroxylation of ZEN and α-ZOL, resolves the mechanism of detoxification and addresses the behaviors of the hydroxylated ZEN and α-ZOL. These results should offer novel bio-detoxification machineries toward ZEN and derivatives.