TY  - THES
T1  - Functional expression of uridine diphospho glucuronosyltransferases in fission yeast
A1  - Buchheit,Daniela
Y1  - 2011/12/13
N2  - Uridine diphospho (UDP) glucuronosyltransferases (UGTs) catalyze the transfer of a sugar moiety from UDP-sugar to endogenous or exogenous compounds. The water solubility of these substances is increased thereby and their excretion from the human body is facilitated. The resulting glycosides, mostly glucuronides, can be pharmacologically relevant and are therefore needed as purified metabolites as reference standards or for toxicity studies. In this work, a whole-cell biotransformation system using recombinant Schizosaccharomyces pombe for the production of glycosides is described. It is based on the coexpression of a single UGT isoform and human UDP glucose-6-dehydrogenase, which delivers UDP-glucuronic acid. The system existed for UGT1A9 and has been extended in this work to be established now for each of the 19 human (and one further polymorphic variant of UGT2B7) and one rat isoform. The system was applied for different purposes. In one study, the usage of alternative UDP-sugar cofactors was investigated and the glucosidation of ibuprofen was shown. Furthermore, enhanced glucoside production rates could be obtained by overexpression of the fission yeast gene fyu1, which was discovered to act as UDP glucose pyrophosphorylase. Investigations of glucuronidation properties of single isoforms and those of different functional groups were studied as well. So, the glucuronidation of two substrates, which just differed in their functional group, being a hydroxyl group or a thiol, was compared.
KW  - Schizosaccharomyces pombe
KW  - Glucuronosyltransferasen
KW  - Biotransformation
KW  - Glucuronidierung
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2011/4522
ER  -