Generation of minimal peptide catalysts based on the macrocyclic scaffold

2018 Fiscal Year Final Research Report

• Project/Area Number: 26220204
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Biomolecular chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Suga Hiroaki 東京大学, 大学院理学系研究科(理学部), 教授 (00361668)
• Research Collaborator: NAGANO Masanobu ; Kato Bashiruddin, Nasir ; Yokosuka Ryota ; Komatsu Yamato ; Hideshima Tomoki ; Hashimoto Atsushi ; Yu Hao ; Takatsuji Ryo ; Ishida Satoshi ; Seino Jongkees ; Umemoto Shiori
• Project Period (FY): 2014-05-30 – 2019-03-31
• Keywords: ペプチド / 天然物 / 翻訳 / リボザイム / ケミカルバイオロジー / 酵素

Outline of Final Research Achievements

Protein enzymes catalyze many pivotal chemical reactions in the body. Despite the great advances of the filed of life science so far, however, how the evolution of enzymes was proceeded is still unknown. We hypothesized that the short peptides would have been main biocatalysts in the evolutional process to the “protein world”. The purpose of this research is to generate minimal peptide catalysts based on the macrocyclic scaffold. To address this, we generated the trillions of constrained macrocyclic peptides and selected out the peptides in which have the acyltransferase activity by means of a combination of the FIT system and the mRNA display technique. After the selection rounds, we discovered the acyltransferase active macrocyclic peptides and the further thorough investigation revealed that the linear short peptide has a self-acylation activity. We believe that this finding accelerates the development of a research for the “peptide world” before the “protein world”.

Free Research Field

生物分子化学

Academic Significance and Societal Importance of the Research Achievements

タンパク質酵素は、生体内の大半の触媒反応を担う生体分子である。しかしながら、現在までの生命科学分野の発展をもってしても、どのように複雑な酵素が進化してきたか、その過程は未だ多くの謎に包まれている。それに対し、本研究の結果、分子量300ほどの極小のペプチドが生体内に存在するアシル化活性を有することを発見できた。本知見は、「酵素の起源」に一石を投じるものであるといえる。またエステル結合を官能基選択的に創り出すアシル化反応は生化学分野のみならず、有機化学分野を含めた幅広い分野で非常に稀であるため学術的価値が高い。