Construction of a New Catalyst Having a Protein Cavity as a Reaction Scaffold

2020 Fiscal Year Final Research Report

• Project Area: Precise Formation of a Catalyst Having a Specified Field for Use in Extremely Difficult Substrate Conversion Reactions
• Project/Area Number: 15H05804
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Osaka University
• Principal Investigator: Hayashi Takashi 大阪大学, 工学研究科, 教授 (20222226)
• Project Period (FY): 2015-06-29 – 2020-03-31
• Keywords: 反応場 / 人工金属酵素 / 生体触媒 / ヘム / 補因子 / 高難度変換反応

Outline of Final Research Achievements

Many metalloenzymes exist in nature and are responsible for various redox reactions and hydrolysis that support biosynthesis and metabolic degradation. The active centers are formed by unique metal cofactors which bind to the protein cavities, and the amino acid residues constituting the cavity act as a coordination sphere, controlling the activity and selectivity of the catalytic reactions. Learning from the structure of the metalloenzymes, our group has designed and created new biocatalysts consisting of artificial metal cofactors and protein reaction fields. These biocatalysts are found to promote several reactions, which may be highly difficult to convert substrates into products via C-H bond activation, C-C bond formation, or hydrogen generation.

Free Research Field

生物無機化学

Academic Significance and Societal Importance of the Research Achievements

酵素は温和な条件下で難しい反応を加速する優れた触媒であるが、反応の種類や基質の選択性で多くの制限がある。研究代表者は、この課題を克服するために、合成金属錯体をタンパク質の空洞に挿入し、新しい生体金属触媒を開発した。本研究では、高難度の反応をつかさどる生体触媒の構築とともに、その反応の中間体の検出を行い、学術的には生物無機化学の分野の中で近年注目されている人工金属酵素の創成に大きく貢献した。また、人工金属補因子を結合するタンパク質マトリクスの構造を遺伝子工学的にチューニングすることにより、反応の加速だけでなく、選択性を制御することを実践し、物質変換を担う生体触媒への提案を行った。