Enantioselective enzyme-catalyzed aziridination enabled by active-site evolution of a cytochrome P450

Christopher C. Farwell, Ruijie K. Zhang, John A. McIntosh, Todd K. Hyster, Frances H. Arnold

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

One of the greatest challenges in protein design is creating new enzymes, something evolution does all the time, starting from existing ones. Borrowing from nature's evolutionary strategy, we have engineered a bacterial cytochrome P450 to catalyze highly enantioselective intermolecular aziridination, a synthetically useful reaction that has no natural biological counterpart. The new enzyme is fully genetically encoded, functions in vitro or in whole cells, and can be optimized rapidly to exhibit high enantioselectivity (up to 99% ee) and productivity (up to 1,000 catalytic turnovers) for intermolecular aziridination, demonstrated here with tosyl azide and substituted styrenes. This new aziridination activity highlights the remarkable ability of a natural enzyme to adapt and take on new functions. Once discovered in an evolvable enzyme, this non-natural activity was improved and its selectivity tuned through an evolutionary process of accumulating beneficial mutations.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalACS Central Science
Volume1
Issue number2
DOIs
StatePublished - May 27 2015

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

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