European scientists have discovered a method to improve the efficiency of the pharmaceutical production through plant biotechnology. The European SmartCell project, coordinated by VTT Technical Research Centre of Finland and funded by the European Commission, showed that biotechnological production offers a cost-effective and environmentally friendly alternative to the chemical synthesis of rare and complex pharmaceutical compounds currently isolated from plants.
Current methods to extract several anticancer alkaloid compounds, such as terpenoid indole alkaloids (e.g., vinblastine and vincristine), from the plant Catharanthus roseus (Madagascar periwinkle) are costly. Plant tissues contain low levels of these alkaloids and chemical synthesis is not an economical alternative because of the highly complex structures and specific stereochemical features of these compounds.
There has been a lot of research on the development of more accessible and cost-effective sources of these drugs. The biotechnological production of high-value plant-derived compounds using plant cell cultures is an attractive and sustainable alternative to extraction from whole plant material. This method, however, is a long and complex process involving multiple enzymatic steps that are still largely uncharacterized at the genetic level.
The aim of the SmartCell is to develop comprehensive knowledge and enabling technologies to control and engineer plants and plant cells for the rational production of high-value plant-derived compounds for industrial use. One of objectives of the SmartCell project was to understand the metabolic pathway leading to the periwinkle terpenoid indole alkaloids. The European SmartCell Consortium reported that it has successfully elucidated the complete upstream segment of the terpenoid indole alkaloid biosynthesis pathway. The article has been published in Nature Communications. The complete pathway of 12 enzymes was reconstructed in tobacco plants, paving the way for cost-effective production of diverse therapeutic compounds.
Cell-culture technologies were also developed, and the cultivation of the plant cells was scaled-up using bioreactors at VTT's pilot laboratory in Finland. "The use of plant cells as real green chemical factories is now becoming feasible for the first time. The technology developed and the experience gained on terpenoid indole alkaloids in this project can be utilized and applied to other compounds and plants as well," said Dr Kirsi-Marja Oksman-Caldentey, project coordinator from VTT, in a press statement.