A Non-Canonical Proximal Heme Ligand Affords an Efficient Peroxidase in a Globin Fold

Research output: Contribution to journalArticle

  • External authors:
  • Moritz Pott
  • Takahiro Hayashi
  • Takahiro Mori
  • Peer R. E. Mittl
  • Donald Hilvert


Expanding the range of genetically encoded metal coordination environments accessible within tunable protein scaffolds presents excellent opportunities for the creation of metalloenzymes with augmented properties and novel activities. Here, we demonstrate that installation of a non-canonical Nδ-methyl histidine (NMH) as the proximal heme ligand in the oxygen binding protein myoglobin (Mb) leads to substantial increases in heme redox potential and promiscuous peroxidase activity. Structural characterization of this catalytically modified myoglobin variant (Mb NMH) revealed significant changes in the proximal pocket, including alterations to hydrogen bonding interactions involving the prosthetic porphyrin cofactor. Further optimization of Mb NMH via a combination of rational modification and several rounds of laboratory evolution afforded efficient peroxidase biocatalysts within a globin fold, with activities comparable to those displayed by Nature’s peroxidases.

Bibliographical metadata

Original languageEnglish
JournalJournal of the American Chemical Society
Early online date8 Jan 2018
Publication statusPublished - 2018

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