Microbial Transformation of Zearalenone. 2. Reduction, Hydroxylation, and Methylation Products

Microbial transformations have been employed as a means of preparing analogues of the resorcylic acid lactone zearalenone. Microbial transformation products were initially identified by thin-layer chromatography of fermentation extracts and then prepared by large-scale incubations. Each metabolite was subjected to structural elucidation employing carbon-13 and proton NMR, mass spectrometry, and infrared analysis. Metabolites were identified as α- and β-zearalenol, α- and β-zearalanol, zearalanone, 8’(S)-hydroxyzearalenone, 2,4-dimethoxyzearalenone, and 2-methoxyzearalenone. Binding affinities to rat uterine estrogen receptors were carried out. Only those metabolites having a free 4-phenolic group were capable of binding to the estrogen receptor. However, S’-hydroxyzearalenone, even with a 4-phenolic hydroxyl, did not bind to the receptor. It is possible that hydrogen bonding of the aliphatic hydroxyl groups to the C-6’ carbonyl of zearalenone or equilibrium between the hydroxy ketone and its tautomeric hemiketal may lead to distortion of the conformation of the molecule resulting in loss of binding to the receptor.