Ribosomal synthesis of polyketide-peptide hybrid molecules

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04762
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Biomolecular chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Goto Yuki 東京大学, 大学院理学系研究科(理学部), 准教授 (70570604)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 翻訳合成 / ポリケチド / ペプチド / 擬天然物 / 生合成

Outline of Final Research Achievements

Many polyketide-peptide hybrid molecules have been isolated as bioactive natural products. In this research, we aimed to establish a new method for ribosomal synthesis of peptides bearing unique polyketide-like moieties. To this end, we tested several different synthetic approaches, and eventually demonstrated that peptides with polyketide-like long backbone structures can be expressed by a combination of in vitro translation and posttranslational acyl transfer reaction. This synthetic method has indeed allowed for in vitro ribosomal synthesis of a model bioactive molecule.

Free Research Field

生体分子化学、生体関連化学

Academic Significance and Societal Importance of the Research Achievements

試験管内翻訳合成法は、中分子薬剤候補の化合物ライブラリー構築と探索に近年活発に活用されている。本研究により試験管内翻訳合成で合成できる化合物のバリエーションを拡大させ、実際に生物活性分子を生産できることが実証されたことは、天然物様のポリケチド－ペプチド複合分子を活用した擬天然物創薬戦略の基盤となりえる。