| Project/Area Number |
19K16391
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47050:Environmental and natural pharmaceutical resources-related
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| Research Institution | Institute of Physical and Chemical Research (2020-2021)
Chiba University (2019) |
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Principal Investigator |
Rai Amit 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, 研究員 (60760535)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Camptothecin / Medicinal plants / MIAs / Whole genome sequencing / Phytogenomics / Ophiorrhiza pumila / Comparative genomics / Systems biology / Metabolic gene clusters / Pangenome / Ophiorrhiza japonica / Evolution / Nothapodytes foetida / STR / Secoiridoids / Metabolic gene cluster / OpCYP1 / Pan-Genome / Genome analysis / Metabolite profiling / Specialized metabolites / Systems Biology / Indole Alkaloids / Biosynthesis |
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| Outline of Research at the Start |
Camptothecin (CPT) is one of the most potent anti-cancer compound derived from the plant source. Lack of stable supply for CPT is a grave concern and the reason for the exorbitant cost for cancer treatment. This study aims to understand camptothecin biosynthesis in order to derive a sustainable source of its production.
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| Outline of Final Research Achievements |
During this study, we finalized high-quality genome assemblies of Ophiorrhiza pumila (genome size 440Mb), Ophiorrhiza japonica (genome size 800Mb), and Nothapodytes foetida (genome size 9.79Mb). We also used complete carbon labeling and nitrogen labeling of the Ophiorrhiza pumila metabolome to establish a high-quality metabolome resource to discover unknown intermediates of camptothecin biosynthesis.
Comparative genome analysis showed strictosidine synthase (STR) as the key enzyme that guided the emergence of camptothecin biosynthesis, loss of which resulted in losing the ability of its biosynthesis in coffee. We showed the importance of metabolic gene clusters towards the evolution and retaining the ability to synthesize specialized metabolites in plants. We also identified putative metabolite intermediates from camptothecin biosynthesis. Finally, we established STR knockout lines, which block camptothecin biosynthesis to identify candidate genes associated with biosynthesis pathways.
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| Academic Significance and Societal Importance of the Research Achievements |
This study have produced three high quality genome assemblies of important medicinal plants to explore evolutionary basis of camptothecin biosynthesis, one of the most potent anti-cancer drug in the world. Results and resources will be useful to establish sustainable source of camptothecin.
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