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A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Terpenoid indole alkaloid profile changes in Catharanthus pusillus during development
R Zárate1, C Dirks, R van der Heijden
1Gorlaeus laboratories, Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, PO Box 9502, 2300 RA, Leiden, The Netherlands
Summary
Catharanthus pusillus accumulates high levels of vindoline and catharanthine, key intermediates for anticancer drugs. These terpenoid indole alkaloids are primarily found in young leaves during the plant's flowering and fruiting stages.
Area of Science:
- Plant biochemistry
- Natural product chemistry
- Pharmacognosy
Background:
- Terpenoid indole alkaloids (TIAs) are a diverse class of plant secondary metabolites with significant pharmacological properties.
- Catharanthus species are known sources of valuable TIAs, including anticancer drugs like vinblastine and vincristine.
- Understanding TIA accumulation in different plant organs and developmental stages is crucial for optimizing extraction and potential drug development.
Purpose of the Study:
- To investigate the accumulation patterns of TIAs in Catharanthus pusillus throughout its developmental stages.
- To identify the primary plant organs responsible for TIA biosynthesis and storage.
- To assess the potential of C. pusillus as a source for specific TIA precursors.
Main Methods:
- Analysis of TIA content in various organs (leaves, stems, roots) of C. pusillus at different developmental time points.
- Quantification of major alkaloids, including vindoline and catharanthine, using analytical techniques.
- Correlation of alkaloid levels with plant age and developmental phases (e.g., flowering, fruiting).
Main Results:
- New leaves of C. pusillus were identified as the main repository for TIAs, with vindoline (approx. 4.8 mg/g DW) and catharanthine (approx. 2.2 mg/g DW) being the major metabolites.
- Highest yields of these monomeric alkaloids were observed at 51 and 70 days, coinciding with flowering and fruiting stages.
- Roots showed significant accumulation of tubotaiwine, while stems and older leaves had lower TIA levels. The dimeric alkaloids vincristine and vinblastine were not detected.
Conclusions:
- Catharanthus pusillus is a rich source of vindoline and catharanthine, essential precursors for synthesizing important anticancer dimeric alkaloids.
- TIA accumulation is developmentally regulated, with peak levels in young leaves during reproductive stages.
- This species holds potential for the sustainable production of key TIA intermediates, though it does not accumulate the final dimeric drugs.
