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The nature of chemical innovation: new enzymes by evolution*

  • Frances H. Arnold (a1)
Abstract

I describe how we direct the evolution of non-natural enzyme activities, using chemical intuition and information on structure and mechanism to guide us to the most promising reaction/enzyme systems. With synthetic reagents to generate new reactive intermediates and just a few amino acid substitutions to tune the active site, a cytochrome P450 can catalyze a variety of carbene and nitrene transfer reactions. The cyclopropanation, N–H insertion, C–H amination, sulfimidation, and aziridination reactions now demonstrated are all well known in chemical catalysis but have no counterparts in nature. The new enzymes are fully genetically encoded, assemble and function inside of cells, and can be optimized for different substrates, activities, and selectivities. We are learning how to use nature's innovation mechanisms to marry some of the synthetic chemists’ favorite transformations with the exquisite selectivity and tunability of enzymes.

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Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
Author for correspondence: F. H. Arnold, Division of Chemistry and Chemical Engineering 210-41, California Institute of Technology, Pasadena, CA 91125, USA. Tel.: 626-395-4162; E-mail: fha@cheme.caltech.edu
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*

In honor of Professor Bengt Norden on his 70th Birthday.

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References
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Quarterly Reviews of Biophysics
  • ISSN: 0033-5835
  • EISSN: 1469-8994
  • URL: /core/journals/quarterly-reviews-of-biophysics
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