Research Theme

Development of designer enzymes for biomolecular systems engineering

Keywords

Artificial metalloenzyme, Protein engineering, Coordination chemistry, Intracellular catalysis, Chemo-enzymatic synthesis

Life processes are sustained by a complex network of interconnected biochemical reactions. There has been a growing interest in re-engineering these biochemical reaction networks, which has implications for synthesis of chemicals and medical applications. We believe that the integration of unnatural chemical reactions, not found in nature but developed by humans, into this biochemical reaction network will pave the way for new ventures, leading to the production of various high-value-added compounds and the development of novel drugs with unique modes of action. With this ultimate objective in mind, our group is focusing on artificial enzymes that catalyze unnatural chemical transformations. We are conducting a comprehensive study on the development of artificial enzymes, drawing on coordination chemistry, catalytic chemistry, and protein engineering, as well as the development of technologies for their delivery into cells and organisms.

Research overview : By combining the development of synthetic catalysts through organic synthetic chemistry methods and the modification of protein functions through genetic engineering methods, we can construct designer enzymes that possess non-natural functions. Utilizing these designer enzymes, we aim to design chemical reaction networks within flasks and intervene in biochemical events within cells.

Selected Publications

1. Y. Okamoto, T. Mabuchi, K. Nakane, A. Ueno, S. Sato, “Switching Type I/Type II Reactions by Turning a Photoredox Catalyst into a Photo-Driven Artificial Metalloenzyme” ACS Catal. 2023, 13, 4134-4141.
2. H. J. Davis, D. Häussinger, T. R. Ward, Y. Okamoto,　“A Visible‐Light Promoted Amine Oxidation Catalyzed by a Cp* Ir Complex” ChemCatChem 2020, 12, 4512-4516.
3. Y. Okamoto, R. Kojima, F. Schwizer, E. Bartolami, T. Heinisch, S. Matile, M. Fussenegger, T. R. Ward, “A Cell-penetrating Artificial Metalloenzyme Regulates a Gene Switch in a Designer Mammalian Cell” Nat. Commun. 2018, 9, article number 1943.
4. Y. Okamoto, T. R. Ward “Cross-Regulation of an Artificial Metalloenzyme” Angew. Chem. Int. Ed. 2017, 56, 10156-10160.
5. Y. Okamoto, V. Köhler, T. R. Ward “An NAD(P)H-Dependent Artificial Transfer Hydrogenase for Multienzymatic Cascades” J. Am. Chem. Soc. 2016, 138, 5781-5784.