Polyprenylated xanthones are natural products which are found in various Hypericum species. The prenylation of the core structure which is catalyzed by prenyltransferases considerably increases the bioactivity of a number of products. For example, patulone and hyperixanthone A were found to possess significant antibacterial properties. Polyprenylated xanthones are difficult to synthesize and present in their plant sources in only low amounts, which makes extensive research on these attractive substances challenging. To overcome this obstacle, a transfer of the entire biosynthetic pathway that leads to polyprenylated xanthones from Hypericum to yeast is considered. The chosen model organism (baker's yeast, Saccharomyces cerevisiae) will not only simplify and cheapen handling and cultivation but also result in a more targeted and higher yield of the desired substances. Another possibility is to synthesize unnatural polyprenylated xanthones with increased antibacterial effects by specifically modifying individual biosynthetic steps.
A major challenge for the efficient biosynthesis of polyprenylated xanthones in yeast is the modification of the prenyltransferases to obtain a higher in vivo activity. To receive information about the impact of the modifications made regarding the enzymatic activity of the prenyltransferases, in vivo and in vitro activity assays are performed and analyzed by HPLC.
Furthermore, intracellular localization of the enzymes in yeast cells is part of this work. In Hypericum, the prenyltransferases are integral membrane proteins with multiple transmembrane helices, which are located in the envelope of the chloroplasts. However, yeast cells lack chloroplasts. Therefore, it will be interesting to study the effect of the modifications on both the localization of the prenyltransferases in yeast cells and the enzymatic activity. Reporter fusions of prenyltransferases are localized by fluorescence microscopy.
Name of Doctoral Researcher
Rebekka Mögenburg
Name of Supervisor
Prof. Dr. Ludger Beerhues
Institute / Department
Institute of Pharmaceutical Biology, TU Braunschweig