Frontier Research Institute for Interdisciplinary Sciences
Tohoku University

Researcher

Yasunori Okamoto

Assistant ProfessorAdvanced Basic Science

Mentor Information
Professor
Shin Mizukami (Institute of Multidisciplinary Research for Advanced Materials)
Research Fields Bioinorganic chemistry, Protein engineering, Coordination Chemistry, Chemoenzymatic Synthesis
Research Subjects
  • Artificial metalloenzymes for systems catalysis and intracellular catalysis
Academic Society Membership The Chemical Society of Japan
Research Outline  

A living system consists of myriad biochemical reaction networks. In an engineering spirit, chemists and biologists have respectively re-designed the biochemical reaction networks by using either isolated enzymes and synthetic catalysts (in vitro level engineering) or transgene-encoded proteins (cell level engineering). Because of potential contributions to metabolic engineering or medicinal chemistry, emerging the two approaches, introducing non-canonical chemical transformation into living cells, has become increasingly prevalent.(Chem. Rev. 2019, 119, 829)

Artificial metalloenzymes (ArMs) are constructed by introduction of a synthetic catalyst into a protein scaffold.(Chem. Rev. 2018, 118, 142) The ArMs technology can merge various reactions of homogeneous catalysts with reaction selectivity of enzymes. In addition to this attractive feature as a catalyst, ArMs demonstrate their biocompatibility against biomolecules. Accordingly, ArMs can be promising modules to implement non-canonical reaction into cells, leading to intracellular catalysis. I have been working on delivering ArMs into mammalian cells by attaching a cell-penetrating module to the ArM. This proof-of-concept has been successfully demonstrated.(Nat. Commun. 2018, 9, 1943) For further improvements, however, various challenges need to be addressed. At the FRIS, I am now tackling 1) high-throughput preparation methodologies for ArMs assembly and 2) efficient delivery of large ArM cargo into cells to provide ArMs as a powerful tool to metabolic engineering or medicinal chemistry.

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