2022 Fiscal Year Final Research Report
Heterologous production of Lasso peptides based on bacterial genomic information
| Project/Area Number |
20K05848
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 38040:Bioorganic chemistry-related
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| Research Institution | Shizuoka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中川 博之 国立研究開発法人農業・食品産業技術総合研究機構, 高度分析研究センター, 上級研究員 (30308192)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ペプチド / 異宿主生産 / NMR |
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| Outline of Final Research Achievements |
Middle-molecular-weight peptides are attracting attention for their properties that combine the characteristics of antibodies and low-molecular-weight peptides, and are expected to be applied to medicine. Lasso peptides are cyclic peptides that are attracting attention as targets for drug discovery due to the protease resistance and bioactivity. In this research project, we succeeded in producing several peptides by heterologous production. We established a heterologous production system using Sphingomonas as a host. Furthermore, we have successfully produced a novel peptide koreansin in a different host using the system. The chemical structure was elucidated using NMR and MS spectra, and NOE experiments were performed to clarify the three-dimensional structure.
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| Free Research Field |
応用微生物学
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| Academic Significance and Societal Importance of the Research Achievements |
中分子ペプチドは抗体と低分子の特徴を併せ持つ特性が注目され、医薬への応用が期待されている。特に発酵生産でこの中分子ペプチドを生産することはこれまで難しかった。本研究において、代謝されにくい環状ペプチドの発酵生産法が確立できた。さらに遺伝子組み換えで、配列の異なるペプチドを生合成することも明らかとなった。NMRを用いた化学分析の結果、得られたペプチドは構造的にも非常に安定な三次元構造を有していることを確認することが出来た。今後、本研究で得られた成果は、ペプチド医薬の創出研究に汎用的に用いることが期待できる。
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