Ribosome modification to synthesize peptides containing beta-amino acids

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14332
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: Nagoya University
• Principal Investigator: Fujino Tomoshige 名古屋大学, 工学研究科, 助教 (00772378)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: リボソーム / 無細胞翻訳系 / β-アミノ酸 / D体アミノ酸 / ペプチド

Outline of Final Research Achievements

The aim of this study was modifying ribosome, which is the organelle producing proteins in a cell, to improve the incorporation efficiency of non-proteinogenic amino acids into peptide. We successfully developed a method to pick up the desired mutant ribosome from the pool of highly diverse mutant ribosomes containing random mutations in their rRNA sequences. Although we found the rRNA sequence with an improved activity to introduce D-amino acid into peptide, the expression and purification of the mutant ribosome from E. coli cells were difficult because the structural stability of the mutant ribosome was low.

Free Research Field

進化分子工学

Academic Significance and Societal Importance of the Research Achievements

本研究では、目的の機能を持ったリボソームを、進化分子工学によって取得する手法を開発した。この手法は、本研究で対象としたβ-アミノ酸・D体アミノ酸に限定されず、さまざまな特殊アミノ酸を翻訳可能なリボソームの開発に利用できる。今後、特殊アミノ酸の翻訳が自由に行えるようになれば、現在注目されている進化分子工学を利用したペプチド薬剤の開発など、実用的な分野への応用も可能になると期待される。