Selective Synthesis of the Human Drug Metabolite 5′-Hydroxypropranolol by an Evolved Self-Sufficient Peroxygenase

• Published in: ACS catalysis Vol. 8; no. 6; pp. 4789 - 4799
• Main Authors: Gomez de Santos, Patricia, Cañellas, Marina, Tieves, Florian, Younes, Sabry H. H, Molina-Espeja, Patricia, Hofrichter, Martin, Hollmann, Frank, Guallar, Victor, Alcalde, Miguel
• Format: Journal Article
• Language: English
• Published: American Chemical Society 01.06.2018
• Subjects: human drug metabolites; unspecific peroxygenase; 5′-hydroxypropranolol; peroxygenative activity; peroxidative activity; in situ H2O2 generation system; directed evolution

Propranolol is a widely used beta-blocker that is metabolized by human liver P450 monooxygenases into equipotent hydroxylated human drug metabolites (HDMs). It is paramount for the pharmaceutical industry to evaluate the toxicity and activity of these metabolites, but unfortunately, their synthesis...