European scientists have made ground-breaking discoveries for improving the
efficiency of the production of pharmaceuticals through plant biotechnology.
Biotechnological production offers a cost-effective and environmentally
friendly alternative to the chemical synthesis of rare and complex
pharmaceutical compounds currently isolated from plants. The results have been
achieved in the European SmartCell project coordinated by VTT Technical
Research Centre of Finland.
Several expensive anticancer alkaloid blockbusters used in chemotherapy, such
as terpenoid indole alkaloids - vinblastine and vincristine, are currently
extracted from the plant Catharanthus roseus (Madagascar periwinkle) at
high price. These compounds are used to treat Hodgkin’s lymphoma, breast
cancer, small-cell lung cancer and leukemia. Typically, very low levels
accumulate in plant tissues, but chemical synthesis is not an economical
alternative either due to their highly complex structures and specific
stereochemical features. Internationally, much effort has been invested to
develop 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. However, the biosynthetic pathway leading to these
compounds in plants is long and complex, with multiple enzymatic steps that
are still largely uncharacterized at the genetic level. One of the main goals
of the European Consortium SmartCell was to unravel the metabolic pathway
leading to the periwinkle terpenoid indole alkaloids.
The SmartCell Consortium succeeded in elucidating the complete upstream
segment of the terpenoid indole alkaloid biosynthesis pathway, as described in
a ground-breaking article published in the journal Nature Communications
(Publication date: April 7th, 2014).
The complete pathway of twelve enzymes was reconstructed in tobacco plants,
paving the way for cost-effective production of diverse therapeutic compounds.
Moreover, cell culture technologies were developed, and the cultivation of the
plant cells was scaled-up using bioreactors at VTT’s pilot laboratory in
“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”, says the project coordinator
Dr Kirsi-Marja Oksman-Caldentey from VTT.
SmartCell was a four-year FP7 framework project, funded by the European
Commission with a total budget of 8.5 million euros.
The Consortium was coordinated by Dr Kirsi-Marja Oksman-Caldentey at VTT. It
comprised 14 academic partners from leading European universities and research
institutes, and four industrial members.
The SmartCell project aimed at developing 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.
The findings of the SmartCell project have thus far resulted in a total of 118
peer-reviewed scientific publications.
The European Consortium SmartCell: http://www.smart-cell.org
K. Miettinen, L. Dong, N. Navrot, T. Schneider, V. Burlat, J. Pollier, L.
Woittiez, S. van der Krol, R. Lugan, T. Ilc, R. Verpoorte, K.-M.
Oksman-Caldentey, E. Martinoia, H.J. Bouwmeester, A. Goossens, J. Memelink &
D. Werck-Reichhart (2014): The seco-iridoid pathway from Catharanthus roseus.
Nature Communications. Publication date: April 7th, 2014.
Photo: The main source of
vinblastine and vincristine is the Madagascar periwinkle (Catharanthus
roseus), also known as an ornamental plant. The SmartCell Consortium
succeeded in elucidating the complete upstream segment of the biosynthetic
pathway leading to these valuable anticancer pharmaceuticals, and thus
creating the basis for their biotechnological production. (Photo: VTT)