Vinca alkaloids such as vincristine and vinblastine are crucial for the treatment of several types of cancers. However, these drugs are also in short supply, because they can only be found in small amounts in one plant species, the Madagascar periwinkle.
Unfortunately, the biosynthetic pathway that the Madagascar periwinkle uses to produce vincristine and vinblastine isn’t yet fully understood. However, if we find a way to manipulate that pathway, then we may be able to upregulate production of these molecules or transfer the pathway into another plant species that is easier to grow. Recently, a team of researchers identified the last two enzymes in the vinblastine biosynthesis pathway.
To begin, this team searched periwinkle RNA expression data for genes that are expressed at the same time as known vinblastine synthesis enzymes. Consequently, they found two candidate genes, which they named taberosine synthase (TS) and catharanthine synthase (CS). They first tried knocking out the genes’ expression in periwinkle plants. As a result, plants without TS and CS expression made much less precursors to vinblastine.
Next, they expressed TS and CS in the leaves of tobacco plants. Under these circumstances, the leaves formed detectable levels of vinblastine precursors.
Conceivably, these enzymes could be used to produce vinblastine and other medically important vinca alkaloids in other plant species.
- Vincristine Sulfate
- Vinblastine Sulfate
- Vindoline
- Vinleurosine Sulfate
- Vinorelbine Base
- Vinorelbine Ditartrate
- Vinpocetine
- Catharanthine
Caputi L, Franke J, Farrow SC, et al. Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. Science. 2018 Jun 15;360(6394):1235-1239. PMID: 29724909