| Project/Area Number |
20K05787
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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 |
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| Project Period (FY) |
2020-04-01 – 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 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | メタボロミクス / 抗生物質 / Streptomyces / Actinomyces / 代謝経路 / microbiology / 微生物学 / Streptomyces coelicolor / antibiotics production / metabolomics / antibiotics control / gamma-butyrolactones / induction / strain improvement |
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| Outline of Research at the Start |
A combination of untargeted metabolomics and synthetic biology approaches will be used for a systematic and comprehensive study on the metabolism of an engineered Streptomyces coelicolor M145. This strain will be used as a background strain to elucidate the metabolic changes that occur upon changes in environmental stimuli. Using untargeted metabolomics approach, the activation of cryptic biosynthetic gene clusters for new antibiotics discovery will be monitored.
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| Outline of Final Research Achievements |
This is the first study to apply metabolome-based multi-omics analysis in S. coelicolor strains to identify metabolites that contribute to antibiotic production and to partially elucidate their mechanisms of action. Metabolomic analysis showed that antibiotic production correlated with the amount of intracellular and extracellular cAMP, and that the addition of cAMP to the culture medium increased the productivity of antibiotics such as actinorhodin and germicidin. Metabolomic analysis of cAMP addition to the cell culture suggests the importance of guanine in the positive regulation of cAMP.The knowledge on the mechanism of antibiotics control and induction resulted from this study can contribute to increasing antibiotics production and discovery of new antibiotics in the future
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，代謝物および遺伝子発現の点から多くのデータを取得しており，今後の当該分野における各種オミクス解析の結果と統合することで，S. coelicolor における抗生物質生産に関連した制御機構の更なる解明が期待される．また本研究で得られた知見は，抗生物質生産における制御機構の理解の一端を広げることを可能にする知見である．本知見の作用機序の更なる理解によって，新規抗生物質の発見を可能にすることや抗生物質のより効率的な生産に資する知見が特定されることが期待される．
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