SmartCell to use plant cells as pharmaceutical factories

SmartCell, an EU-funded project, has been awarded EUR 6 million to develop tools to synthesise valuable pharmaceutical products using plant cells. The project is a consortium of 18 partners from the EU, Switzerland and the US. The partners include 14 leading research institutes and universities as well as 2 small- and medium-sized enterprises and 2 major industrial enterprises. The project has a total budget of EUR 8.5 million and is scheduled to run for 4 years.

In 2004 an estimated one-fourth of all prescribed pharmaceuticals in industrialised countries contained compounds derived from plants. Some well-known plant-based drugs include morphine, codeine, quinine and digitoxin steroids. It has so far not been possible to produce synthetic substitutes that are as pharmacologically efficient and specific.

Living plants produce a wide variety of 'secondary metabolites', compounds that help the plant adapt to its environment. These secondary metabolites (resin, for example) are produced in small amounts over very long periods of time; in the case of trees it might take several years. They are sometimes considered to be waste products of plant metabolism but are of tremendous pharmaceutical significance.

Most secondary metabolites (also called phytopharmaceuticals) are currently isolated from whole, living plants because their chemical synthesis is extremely difficult and costly. However, biosynthesis is a complex and poorly understood process, and yields are low. In addition, many of the plants that produce these high-value compounds are difficult to cultivate or are overharvested.

Plant cells could be used to produce valuable pharmaceutical compounds on a large scale much in the same way that microbes are used to produce antibiotics. Dr Oksman-Caldentey of VTT Technical Research Centre, Finland, co-ordinator of the project, explained, "The difference is that in microbes the process of producing antibiotics is short and relatively simple; by contrast, the exact mechanisms by which plants can produce these small-molecular-weight compounds (are) poorly understood."

The SmartCell consortium will combine the efforts of scientists specialising in several areas of research to describe the mechanisms of secondary metabolite production. Experts in plant science, pharmacognosy (the study of medicines derived from natural sources), microbiology, phytochemistry, biochemistry, molecular biology, and fermentation technology will apply their wide knowledge base to the study of plant metabolic pathways in isolated, cloned cells. Their new understanding will be used to develop tools that exploit these secondary metabolic pathways, synthesising high volumes of pharmaceutically valuable compounds quickly. In effect, they will manipulate plant cells to act as 'green factories'.

The focus of SmartCell's initial activities will be the synthesis of terpenes, which are produced by a wide variety of plants (particularly conifers). Some examples of well-known terpene derivatives include steroids, menthol, camphor and cannabinoids. They are being used in SmartCell's initial research because preliminary studies have been promising and also because there are already some good working examples (paclitaxel, an anti-cancer drug originally extracted from the bark of 60-year-old Pacific yew trees, is produced partially from plant cell cultures). If all goes well, the same tools used to synthesise terpenes will be applied to engineer other desirable compounds.

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