Activation of fungal silent secondary metabolite gene clusters using the CRISPR/Cas9 system.
| Project/Area Number |
18K05420
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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 38020:Applied microbiology-related
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| Research Institution | The University of Tokyo (2021-2022)
Institute of Physical and Chemical Research (2018-2020) |
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Principal Investigator |
YUN CHOONGSOO 東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (40432801)
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| Co-Investigator(Kenkyū-buntansha) |
本山 高幸 国立研究開発法人理化学研究所, 環境資源科学研究センター, 専任研究員 (70291094)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 菌類 / 二次代謝 / ゲノム編集 / 糸状菌 / CRISPR/Cas9 |
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| Outline of Final Research Achievements |
The recent large-scale sequencing of fungal genomes has shown that fungi are richer in secondary metabolism-related genes than once believed. However, the majority of these genes are silent under laboratory culture conditions. Silent gene clusters represent a promising resource for the development of new therapeutic agents. Unfortunately, the characterization of secondary metabolites produced by these clusters is frequently hampered owing to our inability to express these gene clusters. To overcome this bottleneck, here I conducted the research project for activation of fungal silent secondary metabolite biosynthesis gene clusters using the powerful genome editing technology, CRISPR/dCas9-transcriptional activation factor system and I succeed that activating the tenuazonic acid production in P. oryzae using this system.
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| Academic Significance and Societal Importance of the Research Achievements |
昨今、世界的に抗生物質が効かない多剤耐性菌の増加や新しい感染症の拡散が問題視されているなか、新規抗生物質や治療剤のリード化合物になり得る糸状菌二次代謝産物発掘は大いに注目されている。この観点から休眠二次代謝遺伝子群の活性化及び代謝産物の獲得は社会に大きく貢献できると考えられる。本研究で提案したCRIPSR/dCas9システムを応用した休眠二次代謝遺伝子群の活性化方法は新規有用代謝産物獲得に適用できる可能性を示した。まだ細部的なシステムの改良などが必要であるが今後の研究で解決できると考えている。
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Report
(6 results)
Research Products
(9 results)
