2021 Fiscal Year Final Research Report
Systems biology approach to unravel biosynthesis and evolution of camptothecin, a potent anti-cancer natural product
| Project/Area Number |
19K16391
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 47050:Environmental and natural pharmaceutical resources-related
|
|---|
| Research Institution | Institute of Physical and Chemical Research (2020-2021)
Chiba University (2019) |
|---|
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)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | Camptothecin / Medicinal plants / MIAs / Whole genome sequencing / Phytogenomics / Ophiorrhiza pumila / Comparative genomics / Systems biology |
|---|
| 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.
|
| Free Research Field |
環境および天然医薬資源学関連
|
| 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.
|
