Journal
TETRAHEDRON
Volume 75, Issue 13, Pages 1827-1831Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tet.2019.02.013
Keywords
Unspecific peroxygenase; Human drug metabolites; Dextromethorphan; Tolbutamide; Naproxen; Heme access channel
Categories
Funding
- Spanish Government [BIO2016-79106-R-Lignolution, BI02016-76601-C3-1-R, CTQ2016-70138-R]
- CSIC [PIE-201580E042]
- Comunidad de Madrid Synergy CAM Project [Y2018/BIO-4738-EVOCHIMERA-CM]
- Ministry of Science, Innovation and Universities (Spain) [BES-2017-080040]
- CONACYT (Mexico)
Ask authors/readers for more resources
By mimicking the role of human liver P450 monooxygenases, fungal unspecific peroxygenases (UPOs) can perform a range of highly selective oxyfunctionalization reactions on pharmacological compounds, including O-dealkylations and hydroxylations, thereby simulating drug metabolism. Here we have benchmarked human drug metabolite (HDM) synthesis by several evolved UPO mutants, focusing on dextromethorphan, naproxen and tolbutamide. The HDM from dextromethorphan was prepared at the semi-preparative scale as a proof of production. The structural analysis of mutations involved in the synthesis of HDMs highlights the heme access channel as the main feature on which to focus when designing evolved UPOs. These variants are becoming emergent tools for the cost-effective synthesis of HDMs from next-generation drugs. (C) 2019 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available