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. 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.