TY - JOUR T1 - Microbial Models of Mammalian Metabolism JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 301 LP - 310 VL - 25 IS - 3 AU - Cecile Moussa AU - Patrick Houziaux AU - Bernard Danree AU - Robert Azerad Y1 - 1997/03/01 UR - http://dmd.aspetjournals.org/content/25/3/301.abstract N2 - This study was undertaken to validate the use of microbial biotransformation systems for drug metabolism studies. Thymoxamine 1 was rapidly hydrolyzed to desacetylthymoxamine (DAT) 2 by numerous fungi. Other known animal metabolites, such asN-desmethyl-desacetylthymoxamine 3 and desacetylthymoxamine-O-sulfate 6, were produced from DAT by Mucor rouxii and Mortierella isabellina. DAT-N-oxide 5, a putative animal microsomal metabolite, was also produced by M. isabellina. In addition, a few strains (such as Actinomucor elegans, Mucor hiemalis, and Mucor janssenii) produced a glycosylated metabolite that was identified by high-resolution1H- and 13C-NMR, MS, and enzymatic hydrolysis as the corresponding [4-(2-dimethylaminoethoxy)-5-isopropyl-2-methyl-phenyl]-1-β-d-glucopyranoside 7. A similar glucosylation reaction was observed when thymohydroquinone 10 was incubated with A. elegans. Several strains were able to produce transiently thymohydroquinone from DAT-N-oxide 5, possibly through a β-elimination mechanism. The American Society for Pharmacology and Experimental Therapeutics ER -