An Artificial Heme Enzyme for Cyclopropanation Reactions

Lara Villarino, Kathryn Splan, Eswar Reddem, Cora Gutiérrez de Souza, Lur Alonso-Cotchico, Agustí Lledós, Jean-Didier Maréchal, Andy-Mark Thunnissen, Gerard Roelfes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)
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Abstract

An artificial heme enzyme was created through self-assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre-catalytic structures.

Original languageEnglish
Pages (from-to)7785-7789
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number26
Early online date2018
DOIs
Publication statusPublished - 25-Jun-2018

Keywords

  • artificial metalloenzymes
  • biocatalysis
  • carbenes
  • enzyme design
  • heme enzymes
  • OLEFIN CYCLOPROPANATION
  • MULTIDRUG RECOGNITION
  • METALLO-HYDRATASE
  • CARBENE TRANSFER
  • CYTOCHROME-C
  • DESIGN
  • IRON
  • MYOGLOBIN
  • LMRR
  • PROTEINS

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