Beyond the isoprene rule – Synthesis of uncommon terpenes

Terpenes are the largest natural product class, for which more than 70.000 compounds are currently known. Among them, many substances are used by mankind as pharmaceuticals (e.g. artemisinin and taxol), flavor and fragrance compounds (e.g. menthol, santalol and sclareol) or structural materials (e.g. polyisoprene). Despite the extremely high structural diversity, all terpene backbones are constructed out of only two building blocks IPP (isopentenyl pyrophosphate) and DMAPP (dimethylallyl pyrophosphate), both containing five carbon atoms. This fact is reflected in the isoprene rule which is based on the findings and interpretations of Otto Wallach and Leopold Ružička and determines the number of carbon atoms in primary terpenoid products to be a multiple of 5. IPP and DMAPP can be combined to longer terpenoid precursors, e.g. the C₁₀-molecule GPP (geranyl pyrophosphate) or the C₁₅-molecule FPP (farnesyl pyrophosphates).

Our group aims at an extension of the cellular repertoire of prenyl pyrophosphates, which can be used as building blocks in terpene biosynthesis pathways to expand the possible chemical space of this important compound class. The current main approach is the use of different prenyl pyrophosphate methyltransferases to incorporate additional methyl groups into the terpenoid backbone. We see the most obvious way to apply the new biosynthetic possibilities in the synthesis of derivatives of known pharmaceuticals or fragrances, in order to create altered bioactivities or odor properties.

"New to nature" terpenes for liquid fuels from renewable raw materials

The substance class of terpenoid hydrocarbons is discussed as a resource for molecules able to substitute petrochemistry-based liquid fuels. Research done mainly by U.S. research groups and companies has already laid the foundation for microbial de novo synthesis of various terpenes including potential fuel molecules. However, it will not be possible to use a pure terpene directly in existing internal combustion engines. Instead, a mixture of various hydrocarbons is needed to obtain an engine fuel, which is compatible with the existing infrastructure.

With this research project, an extension of the product range of microbial terpene production processes is explored. During the project, the technological foundation for the synthesis of "new to nature" terpenes with bacterial enzymes will be laid. This aspect provides the substance diversity required for biotechnological production of "drop-in" fuels in a medium- and long-term perspective. Moreover, the variety of uncommon terpenoid structures might be also applied as aroma and pharma compounds.