2021 Fiscal Year Annual Research Report
Systems biology approach to unravel biosynthesis and evolution of camptothecin, a potent anti-cancer natural product
| Project/Area Number |
19K16391
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| Research Institution | Institute of Physical and Chemical Research |
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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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| Keywords | Metabolic gene clusters / Ophiorrhiza pumila / Pangenome / Comparative genomics / Ophiorrhiza japonica / Evolution / Camptothecin / Nothapodytes foetida |
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| Outline of Annual Research Achievements |
The research achievements are as follows- (1) We established a high-quality genome assembly of camptothecin producing plant Ophiorrhiza pumila, one of the best plant genomes assembled ever. (2) We identified critical enzymes involved in the biosynthesis of camptothecin. (3) We established a pan-genome for monoterpene indole alkaloids biosynthesis using whole-genome assemblies of O. pumila, Catharanthus roseus, Camtotheca accuminata, and Gelsemium sempervirens. (4) We established the whole-genome assembly of Ophiorrhiza japonica, a close species of Ophiorrhiza pumila, which does not produce camptothecin. (5) We also established whole genome assembly for Nothapodytes foetida, which has a genome size of 9.79Gb. (6) In this study, we established metabolome resources to expand the study on camptothecin biosynthesis using complete carbon and nitrogen labeling approaches. (7) In this study, we established the emergence of STR (strictosidine synthase enzyme) as the key evolutionary event for the evolution of MIAs and camptothecin biosynthesis. Our results proposed a way to identify putative candidate genes associated with camptothecin biosynthesis. (8) We established STR knockout, an enzyme that catalyzes the biosynthesis of strictosidine. The line established in this study will be used to identify candidate genes associated with camptothecin biosynthesis, which will be used for further functional characterization. (9) We performed transcriptome analysis using Ophiorrhiza pumila hairy roots for four phytohormones across 8-time points. The coexpression analysis is ongoing.
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| Remarks |
The website is Ophiorrhiza pumila genome database, publically available, for use to study MIA biosynthesis in plants.
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