Microbial models of mammalian metabolism: stereoselective metabolism of warfarin in the fungus Cunninghamella elegans.
作者： Yiu W. J. Wong , Patrick J. Davis
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摘要: Biotransformation stereoselectivity of warfarin was studied in the fungus Cunninghamella elegans (ATCC 36112) as a model mammalian metabolism. This organism previously shown to produce all known phenolic metabolites warfarin, including 6-, 7-, 8-, and 4′-hydroxywarfarin, unreported 3′-hydroxywarfarin, well diastereomeric alcohols, diketone, aliphatic hydroxywarfarins. Using S-warfarin R-warfarin substrates, an HPLC assay with fluorescence detection analyze metabolite profiles, biotransformation found be highly substrate product stereoselective. Both aromatic hydroxylation ketone reduction were stereoselective for R-warfarin. Ketone enantiomers exhibited high level that predominantly reduced its S-alcohol, while primarily corresponding R-alcohol.
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