ArticlePlant physiology2004
Biosynthesis of camptothecin. In silico and in vivo tracer study from [1-13C]glucose.
Article in Plant physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Development of phytochemical genomics: From decoding metabolome to functional genomics and biotechnology of plant metabolism.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- Agrobacterium-Mediated Genetic Transformation in Ashwagandha (Withania somnifera).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Bioprocesses optimization and anticancer activity of camptothecin from Aspergillus flavus, an endophyte of in vitro cultured Astragalus fruticosus.Molecular biology reports · 2022Article
- Production, Bioprocessing and Anti-Proliferative Activity of Camptothecin fromMolecules (Basel, Switzerland) · 2022Article
- Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin inHorticulture research · 2022Article
- The transcription factor OpWRKY2 positively regulates the biosynthesis of the anticancer drug camptothecin in Ophiorrhiza pumila.Horticulture research · 2021Article
- Metabolic and transcriptional analyses in response to potent inhibitors establish MEP pathway as major route for camptothecin biosynthesis in Nothapodytes nimmoniana (Graham) Mabb.BMC plant biology · 2019Article
- Tracing the biosynthetic origin of limonoids and their functional groups through stable isotope labeling and inhibition in neem tree (Azadirachta indica) cell suspension.BMC plant biology · 2018Article
- High-throughput sequencing and de novo transcriptome assembly of Swertia japonica to identify genes involved in the biosynthesis of therapeutic metabolites.Plant cell reports · 2016Article
- Function of AP2/ERF Transcription Factors Involved in the Regulation of Specialized Metabolism inFrontiers in plant science · 2016Article
- Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila.Scientific reports · 2015Article
- Hairy root transformation using Agrobacterium rhizogenes as a tool for exploring cell type-specific gene expression and function using tomato as a model.Plant physiology · 2014Article
- Article
- Coupling deep transcriptome analysis with untargeted metabolic profiling in Ophiorrhiza pumila to further the understanding of the biosynthesis of the anti-cancer alkaloid camptothecin and anthraquinones.Plant & cell physiology · 2013Article
- Article
- Transcriptome analysis reveals putative genes involved in iridoid biosynthesis in Rehmannia glutinosa.International journal of molecular sciences · 2012Article
- Contribution of the mevalonate and methylerythritol phosphate pathways to the biosynthesis of dolichols in plants.The Journal of biological chemistry · 2008Article
- NMR analysis of plant nitrogen metabolism.Photosynthesis research · 2005Review
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Authors and funding
8 authors.
Funding
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Abstract
Camptothecin derivatives are clinically used antitumor alkaloids that belong to monoterpenoid indole alkaloids. In this study, we investigated the biosynthetic pathway of camptothecin from [1-13C]glucose (Glc) by in silico and in vivo studies. The in silico study measured the incorporation of Glc into alkaloids using the Atomic Reconstruction of Metabolism software and predicted the labeling patterns of successive metabolites from [1-13C]Glc. The in vivo study followed incorporation of [1-13C]Glc into camptothecin with hairy roots of Ophiorrhiza pumila by 13C nuclear magnetic resonance spectroscopy. The 13C-labeling pattern of camptothecin isolated from the hairy roots clearly showed that the monoterpene-secologanin moiety was synthesized via the 2C-methyl-D-erythritol 4-phosphate pathway, not via the mevalonate pathway. This conclusion was supported by differential inhibition of camptothecin accumulation by the pathway-specific inhibitors (fosmidomycin and lovastatin). The quinoline moiety from tryptophan was also labeled as predicted by the Atomic Reconstruction of Metabolism program via the shikimate pathway. These results indicate that camptothecin is formed by the combination of the 2C-methyl-D-erythritol 4-phosphate pathway and the shikimate pathway. This study provides the innovative example for how a computer-aided comprehensive metabolic analysis will refine the experimental design to obtain more precise biological information.
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