PT  - JOURNAL ARTICLE
AU  - Călin-Aurel Drăgan
AU  - Daniela Buchheit
AU  - Daniel Bischoff
AU  - Thomas Ebner
AU  - Matthias Bureik
TI  - Glucuronide Production by Whole-Cell Biotransformation Using Genetically Engineered Fission Yeast <em>Schizosaccharomyces pombe</em>
AID  - 10.1124/dmd.109.030965
DP  - 2010 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 509--515
VI  - 38
IP  - 3
4099  - http://dmd.aspetjournals.org/content/38/3/509.short
4100  - http://dmd.aspetjournals.org/content/38/3/509.full
SO  - Drug Metab Dispos2010 Mar 01; 38
AB  - Drug metabolites generated by UDP glycosyltransferases (UGTs) are needed for drug development and toxicity studies, especially in the context of safety testing of metabolites during drug development. Because chemical metabolite synthesis can be arduous, various biological approaches have been developed; however, no whole-cell biotransformation with recombinant microbes that express human UGTs was yet achieved. In this study we expressed human UDP glucose-6-dehydrogenase together with several human or rat UGT isoforms in the fission yeast Schizosaccharomyces pombe and generated strains that catalyze the whole-cell glucuronidation of standard substrates. Moreover, we established two methods to obtain stable isotope-labeled glucuronide metabolites: the first uses a labeled aglycon, whereas the second uses 13C6-glucose as a metabolic precursor of isotope-labeled UDP-glucuronic acid and yields a 6-fold labeled glucuronide. The system described here should lead to a significant facilitation in the production of both labeled and unlabeled drug glucuronides for industry and academia. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics