Benchmarking of laboratory evolved unspecific peroxygenases for the synthesis of human drug metabolites

Patricia Gomez de Santos, Fadia V. Cervantes, Florian Tieves, Francisco J. Plou, Frank Hollmann, Miguel Alcalde

Research output: Contribution to journalArticleScientificpeer-review

8 Citations (Scopus)
58 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)1827-1831
Number of pages5
JournalTetrahedron
Volume75
Issue number13
DOIs
Publication statusPublished - 29 Mar 2019

Keywords

  • Dextromethorphan
  • Heme access channel
  • Human drug metabolites
  • Naproxen
  • Tolbutamide
  • Unspecific peroxygenase

Fingerprint Dive into the research topics of 'Benchmarking of laboratory evolved unspecific peroxygenases for the synthesis of human drug metabolites'. Together they form a unique fingerprint.

  • Cite this