Rational design for activation of cryptic natural products in streptomycetes
| Project/Area Number |
18K05390
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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 | Osaka University |
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Principal Investigator |
Kitani Shigeru 大阪大学, 生物工学国際交流センター, 准教授 (10379117)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 応用微生物 / 放線菌 / 抗生物質 / 二次代謝 / シグナル物質 / 抗生物質生産 / 二次代謝シグナル / 休眠二次代謝 / シグナル伝達 |
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| Outline of Final Research Achievements |
Actinomycetes have a large number of secondary metabolite biosynthetic gene clusters, many of which are silent. Activation of the expression of these gene clusters could lead to identifying new bioactive compounds efficiently. This study aimed to awaken the secondary metabolism of actinomycetes by manipulating the signaling pathways that regulate secondary metabolism and to provide new useful compounds. Here, we have identified several actinomycetes that produce butenolide-type Streptomyces hormones, and have shown that the signaling system is universal among actinomycetes. Furthermore, we focused on the β-carboline compounds identified by modification of the Streptomyces-hormone signaling pathway and found a unique β-carboline biosynthetic system, which rare in microorganisms. By modifying this biosynthetic system, we have succeeded in producing non-natural bioactive compounds.
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| Academic Significance and Societal Importance of the Research Achievements |
放線菌の二次代謝産物の多くは、生理活性物質として活用されるにも関わらず、一つの放線菌種が生産する有用物質は極僅かであり、大半の物質がゲノムに潜在する状態にある。本研究により、ブテノライド型の二次代謝シグナルが放線菌に普遍的に存在することが明らかとなった。これにより、本シグナル系の改変は、新たな休眠物質を発掘できる可能性を示した。一方、休眠物質β-カルボリン化合物の生合成系を解析したところ、従来にない合成機構であったこと、また、生合成系の応用は非天然型物質を創出すること、が明らかとなったことから、放線菌潜在能の開拓は生理活性物質の構造多様性拡大に資することが示唆された。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Identification of biosynthetic genes for the β-carboline alkaloid kitasetaline and production of the fluorinated derivatives by heterologous expression2019
Author(s)
Ueda, S., Ikeda, H., Namba, T., Ikejiri, Y., Nishimoto, Y., Arai, M., Nihira, T., Kitani, S.,
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Journal Title
J. Ind. Microbiol. Biotechnol.
Volume: -
Issue: 5
Pages: 739-750
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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