P450BM3-axial mutations: A gateway to non-natural reactivity

Todd K. Hyster, Frances H. Arnold

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations


Enzymes capable of catalyzing non-natural reactions have the potential to alter the way relevant molecules are prepared on-scale. Efforts to this end have largely focused on combining non-natural cofactors with proteins lacking catalytic function to obtain non-natural reactivity. An alternative approach is to utilize a native cofactor to catalyze non-natural reactions. Recently, our group demonstrated that heme-containing cytochrome P450s are able to catalyze the highly selective cyclopropanation of alkenes. Superior activity was observed upon changing the axial cysteine to serine ("P411"). Mutation at the conserved axial ligand has enabled P450s to catalyze other non-natural reactions such as N?H insertion and C?H amination.

Original languageEnglish (US)
Pages (from-to)14-20
Number of pages7
JournalIsrael Journal of Chemistry
Issue number1
StatePublished - Jan 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Chemistry


  • P450
  • amination
  • axial ligation
  • cyclopropanes
  • enzyme catalysis


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