@article{oai:shiga-med.repo.nii.ac.jp:00000181, author = {生城, 真一}, issue = {1}, journal = {滋賀医科大学雑誌}, month = {Mar}, note = {Departmental Bulletin Paper, Xenobiotic phase I and II reactions generally render a compound more water soluble and pharmacologically inactive, thereby eliminating the need for further evaluation. However, if the metabolite forms a toxic compound such as acylglucuronide additional safety assessment may be needed. Glucuronidation is the most common pathway for detoxification and elimination of hydrophobic xenobiotics in mammals. Thus, development of an efficient in vitro synthesis of glucuronides from parent drugs often becomes critical during studies of drug metabolism undertaken in the development of a new pharmaceutical product. In order to produce glucuronides as drug metabolites, we have developed coexpression systems for mammalian cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT), and UDP-glucose dehydrogenase in Saccharomyces cerevisiae cells, and combination between each of human CYPs and UGTs was achieved. Glucuronide formation in yeast cells was performed in reaction medium containing 8% glucose, and most of glucuronides were readily recovered from cell medium. In addition, we have expressed human sulfotransferase (SULT) with CYPs in Saccharomyces cerevisiae cells, and successfully obtained sulfoconjugates from the cell medium. In conclusion, our coexpression systems have made it possible to produce human phase I and phase II metabolites in the milligram to gram scale.}, pages = {a12--a14}, title = {遺伝子改変出芽酵母株を用いた医薬品代謝物調製技術の開発(第11回基礎・臨床融合の学内共同研究発表会)}, volume = {27}, year = {2014} }