Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein

• Published in: Angewandte Chemie International Edition 2019-03, Vol.58 (10), p.3138-3142
• Main Authors: Cho, Inha, Prier, Christopher K., Jia, Zhi‐Jun, Zhang, Ruijie K., Görbe, Tamás, Arnold, Frances H.
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohols; Alkenes; amino alcohols; Anaerobic conditions; Antiviral agents; Bioactive compounds; biocatalysis; Biological activity; Cytochrome; Cytochrome c; Cytochromes; Directed evolution; Enantiomers; heme proteins; Iron; Neurotransmitters; nitrenes; Protein engineering; Proteins; Reactive nitrogen species; Reagents; Selectivity
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201812968

Chiral 1,2‐amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes to unprotected, enantioenriched amino alcohols remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable cytochrome c that directly transforms alkenes to amino alcohols with high enantioselectivity (up to 2500 TTN and 90 % ee) under anaerobic conditions with O‐pivaloylhydroxylamine as an aminating reagent. The reaction is proposed to proceed via a reactive iron‐nitrogen species generated in the enzyme active site, enabling tuning of the catalyst's activity and selectivity by protein engineering. Go direct: A hemoprotein catalyst was engineered to transform alkenes directly to amino alcohols with high enantioselectivity. Derived by directed evolution from a thermostable cytochrome c, the protein catalyst uses O‐pivaloylhydroxylamine to generate a reactive iron‐nitrogen species.