Is the set of 20 Canonical amino acids essential for Life: from viewpoints of alternative genetic codes

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H00985
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Waseda University
• Principal Investigator: Kiga Daisuke 早稲田大学, 理工学術院, 教授 (30376587)
• Co-Investigator(Kenkyū-buntansha): 村田 昇 早稲田大学, 理工学術院, 教授 (60242038)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: タンパク質 / 機械学習 / 合成生物学 / 遺伝暗号 / 進化分子工学

Outline of Final Research Achievements

The purpose of this synthetic-biology study was to pursue the question of whether all 20 amino acids are necessary to constitute life. For the pursuit, protein variants were created by artificial evolution using engineered genetic codes with the support of computational prediction. For predicting the activity of protein mutants, we compared two methods: the ancestral sequence reconstruction method and a deep learning method called variational autoencoder. As a result, we obtained enzymes with sufficient activity without tryptophan for all steps of the glycolytic pathway. As an example of engineering application, we also created an active mutant of GFP without sulfur atoms.

Free Research Field

合成生物学

Academic Significance and Societal Importance of the Research Achievements

天然のタンパク質合成に用いられる20種類のアミノ酸からトリプトファンを除いたセットで生物の中心代謝系である解糖系の活性を構築できたことは、生命の起原と初期進化のシナリオに物質的証拠を提示したことになり、学術的意義が大きい。また、酸化耐性を発揮させるために硫黄原子を持たずとも十分な活性があるタンパク質を創出できたことは、今後のタンパク質産業への貢献が強く期待できる。