Skip to main content

Enantioselective Enzyme-Catalyzed Aziridination Enabled by Active-Site Evolution of a Cytochrome P450

Author(s): Farwell, Christopher C.; Zhang, Ruijie K.; McIntosh, John A.; Hyster, Todd K.; Arnold, Frances H.

To refer to this page use:
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. © 2015 American Chemical Society.
Publication Date: 27-May-2015
Electronic Publication Date: 22-Apr-2015
Citation: Farwell, Christopher C., Zhang, Ruijie K., McIntosh, John A., Hyster, Todd K., Arnold, Frances H. (2015). Enantioselective Enzyme-Catalyzed Aziridination Enabled by Active-Site Evolution of a Cytochrome P450. ACS Central Science, 1 (2), 89 - 93. doi:10.1021/acscentsci.5b00056
DOI: doi:10.1021/acscentsci.5b00056
ISSN: 2374-7943
EISSN: 2374-7951
Pages: 1.2:89 - 93
Type of Material: Journal Article
Journal/Proceeding Title: ACS Central Science
Version: Final published version. This is an open access article.
Notes: ACS Central Science. Volume 1, Issue 2, 27 May 2015, Pages 89-93.

Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.