How Plant Cells Synthesize Pharmaceutical Compounds

Plants produce small-molecular-weight compounds, which are used for example to attract pollinators and in various defence-related reactions. These secondary metabolites are often produced in low quantities in plants. Moreover, they are often structurally very complex molecules, and therefore their chemical synthesis is challenging. Alkaloids, such as morphine and paclitaxel, are secondary compounds which are used as pharmaceuticals. Using cell cultures these often valuable plant-based compounds can be produced in controlled conditions.

In her thesis, VTT research scientist Suvi Häkkinen (MSc, Tech) shows that increased knowledge of regulation of biosynthesis is needed to be able to engineer the production of these compounds in cell cultures.

In this work, a functional genomics-based technology for the discovery of genes involved in plant secondary metabolism was developed. As a result, two novel genes were discovered, which were suggested to be involved in tobacco alkaloid biosynthesis. In addition, a novel alkaloid in tobacco cell cultures was isolated and it was shown to exist in two isomeric forms. When a gene involved in the alkaloid metabolism in Egyptian henbane was overexpressed in tobacco hairy roots, it was shown that added hyoscyamine was efficiently converted into pharmaceutically more valuable scopolamine.

In addition, a majority of the produced scopolamine was secreted out of the cells, which facilitates the product recovery. The transportation of secondary metabolites was also studied by overexpressing a yeast transporter gene in tobacco cell cultures, and it was suggested that PDR5-type transporters can be used to stimulate the secretion of secondary metabolites in plant cells.

Suvi Häkkinen will defend her thesis "A functional genomics approach to the study of alkaloid biosynthesis and metabolism in Nicotiana tabacum and Hyoscyamus muticus cell cultures" at the Helsinki University of Technology (address: Kemistintie 1, Espoo, Finland) on 7 November 2008.