2020 Fiscal Year Research-status Report
Metabolomics-driven approach to understand antibiotics induction ability mechanism in Streptomyces coelicolor
| Project/Area Number |
20K05787
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| Research Institution | Osaka University |
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Principal Investigator |
PUTRI SASTIA 大阪大学, 工学研究科, 助教 (50729796)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | metabolomics / antibiotics production / induction / Streptomyces / strain improvement |
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| Outline of Annual Research Achievements |
In this study, liquid chromatography tandem mass spectrometry (LC-MS/MS)based metabolome analysis with wide metabolite coverage and RNAseq-based transcriptome analysis were employed for comparative analyses of strains with differing antibiotic production phenotypes. To identify the possible factors affecting secondary metabolite production and to provide a more detailed understanding of the regulation of secondary metabolites, a comparative multi-omics analysis was conducted on S. coelicolor strains that either produce the secondary metabolite actinorhodin (Act) or lack most secondary metabolite biosynthesis pathways, including Act. The results revealed that antibiotic production is correlated with cAMP levels, and cAMP supplementation to S. coelicolor culture led to improvements of cell growth and antibiotic production. In addition, cAMP-supplemented S. coelicolor cultures showed an increase of guanine levels and the expression level of purine metabolism genes. Inhibition of guanine utilizing reactions by the analog 7-methylguanine confirmed that reactions inhibited by 7-methylguanine mediate the positive effect of cAMP supplementation on growth and antibiotic production.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
In the first year of this project, the first comprehensive metabolite profiling of Streptomyces coelicolor was demonstrated and resulted in new insight on the correlation between cAMP and actinorhodin production. Two manuscripts in good peer reviewed journals describing the metabolome of Streptomyces coelicolor during the production of antibiotics were published in this fiscal year.
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| Strategy for Future Research Activity |
From the work conducted in FY2020, a new hypothesis is generated on the role of specific metabolite in controlling antibiotics production, namely cAMP and purine metabolism. Construction of strains with improved antibiotics production and new ways to control antibiotics production will be the focus of FY2021. In addition, comparative metabolite analysis will be conducted to investigate the role of gamma butyrolactone signaling molecule and its relationship to actinorhodin production.A combination of transcriptome and metabolome analysis is expected to reveal new insights on how to control the production of antibiotics in S. coelicolor.
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| Causes of Carryover |
Due to the COVID 19 pandemic situation, several plans to visit domestic conferences had to be cancelled and there is no cost on travel expenses. The usage plan for next fiscal year will be to purchase consumables and attend conference.
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