Genetic Optimization of Metalloenzymes: Enhancing Enzymes for Non-Natural Reactions

Todd K. Hyster, Thomas R. Ward

Research output: Contribution to journalReview articlepeer-review

118 Scopus citations


Artificial metalloenzymes have received increasing attention over the last decade as a possible solution to unaddressed challenges in synthetic organic chemistry. Whereas traditional transition-metal catalysts typically only take advantage of the first coordination sphere to control reactivity and selectivity, artificial metalloenzymes can modulate both the first and second coordination spheres. This difference can manifest itself in reactivity profiles that can be truly unique to artificial metalloenzymes. This Review summarizes attempts to modulate the second coordination sphere of artificial metalloenzymes by using genetic modifications of the protein sequence. In doing so, successful attempts and creative solutions to address the challenges encountered are highlighted.

Original languageEnglish (US)
Pages (from-to)7344-7357
Number of pages14
JournalAngewandte Chemie - International Edition
Issue number26
StatePublished - Jun 20 2016

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Catalysis


  • asymmetric synthesis
  • directed evolution
  • hybrid catalysts
  • metalloenzymes


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