2021 Fiscal Year Final Research Report
Elucidation of the biosynthetic pathway of terrestrial tetrodotoxin via metagenomic analysis
Project/Area Number |
20K15405
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
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Research Institution | Tohoku University |
Principal Investigator |
Kudo Yuta 東北大学, 学際科学フロンティア研究所, 助教 (60824662)
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Project Period (FY) |
2020-04-01 – 2022-03-31
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Keywords | テトロドトキシン / イモリ / 生合成 / 構造解析 / メタゲノム |
Outline of Final Research Achievements |
The biosynthesis of tetrodotoxin (TTX), a potent neurotoxin distributed in pufferfish and newt, has not yet been elucidated. With the aim of elucidating the biosynthetic pathway of TTX in terrestrial organisms, we conducted metagenomic analysis of environmental DNA obtained from the toxic newt habitats, and screening for new TTX-related compounds from toxic newts. New TTX analogues was identified from the toxic newt extract. The structure of the previously reported TTX analogue was revised in this study. We discovered novel cyclic guanidino compounds including two novel skeletal tricyclic compounds. The chemical structures of the obtained compounds provided insight into the biosynthetic/shunt pathways of TTX in terrestrial organisms. The fosmid metagenomic library was prepared from the environmental samples of the toxic newt habitat. PCR screening of possible biosynthetic genes of TTX and sequencing of the library by Next Generation Sequencer were performed.
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Free Research Field |
天然物化学
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Academic Significance and Societal Importance of the Research Achievements |
最も有名な自然毒の一つで、重要な食中毒原因物質でもあるテトロドトキシン(TTX)の生合成に関する研究を行った。有毒イモリより新たなTTX類縁体を2種同定することができ、さらに既報の成分1種の構造改訂を行った。新規骨格構造を持つ化合物2種を含む新規環状グアニジノ化合物を得て、その構造を詳細に解析した。陸上におけるTTXの推定生合成およびシャント経路において多様な化合物が生成することを示し、新規化合物の構造から生合成経路への新たな知見が得られたことから、学術的・社会的な意義がある。有毒イモリ生息地の環境メタゲノムの塩基配列を解読し、今後、生合成経路の解明に貢献し得るデータが取得できた。
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