Enzyme experts trying to make the anticancer APIs vincristine and vinblastine with engineered cell lines say the technology could be used to produce a wide range of plant-derived drug actives including alkaloids like morphine.
The claim was made by scientists at VTT Technical Research Centre in Finland who are trying to replicate the chemical pathway through which vincristine and vinblastine are synthesised in the Madagascan periwinkle (Catharanthus roseus) plant.
Project leader Kirsi-Marja Oksman-Caldentey told us making the expensive drug actives in culture is attractive because Madagascan periwinkles yield only small amounts - around 0.0003% of the leaf dry weight – meaning hundreds of kilograms of plants are needed to obtain 1 g of product.
“However,” she continued “we have worked out the major part of the extremely long and complicated terpenoid indole alkaloid up to strictosidine, a major intermediate, but not yet solved the whole pathway.”
Oksman-Caldentey said her team identified 12 enzyme encoding genes involved in strictosidine production and confirmed the finding by reconstructing the partial synthesis pathway in a tobacco plant
Cell culture tools
The research project – which Oksman-Caldentey describes as being about “half way” completed – was funded by the European Commission as part of its Seventh Framework project (FP7) has resulted in the development of a lot of analysis tools.
“This European project took 4 years to obtain these results and a lot of different tools were developed to speed up the gene discovery and the functional analysis. Also the same tools can be used to other medicinal plants” she said.
Last month, in-Pharmatechnologist.com reported about GSK’s efforts to convince the Australian government to allow cultivation of opium poppies outside drought striken Tasmania to bolster limited global supplies of morphine for drug production .
But, if it can be scaled-up successful, the cell culture technology VTT is developing could help make prevent shortages according to Oksman-Caldentey who said: “The enabling technologies we have developed are largely applicable to the other plant species.
"Indeed, there are many important medicinal plants which are used for obtaining pharmaceuticals, for example the opium poppy,” she continued, adding that “chemical synthesis is not a feasible option due to highly complex chemical structures."