Thorvaldsensvej 40, 1871 Frederiksberg C
Plants produce a plethora of specialized metabolites that they are using for interacting with the environment and for defending themselves against biotic and abiotic factors. Among these metabolites, terpenoids is the largest and most diverse class. Our group is interested in the biochemistry of these valuable phytochemicals and by using technologies like transcriptomics, metabolomics and biochemical tools, we aim to elucidate the biosynthetic pathways responsible for the synthesis of selected high value bioactive terpenoids which can be helpful for the wellbeing of our society.
By using pathways we have already elucidated (e.g. forskolin), we are working on understanding the regulatory points of terpenoids biosynthesis and on how we can implement these findings for the heterologous production of high value compounds in a sustainable and environmentally friendly manner. Special focus is given to the plant-based and light-driven heterologous biosynthesis.
In the recent years our group has shown that by using novel technologies, scientific advances and accumulated knowledge, it is possible to elucidate entire biosynthetic pathways in a short and cost-effective time-period. We have managed to elucidate the entire forskolin biosynthetic pathway and to functionally express it in yeast cells. Without significant engineering, yeast cells were able to produce forskolin titers at the range of 40 mg/L, in collaboration with Evolva Biotech. Thus, we have shown that yeast can be a suitable production platform for high-value terpenoids, and a suitable host for expressing the recalcitrant CYP enzymes in a functional way. Additional we have managed to manipulate in vivo the function of CYPs enzymes, to improve their efficiency and products specificity via enzymes engineering.
In a similar manner we have identify enzymes participating in the early steps of the pathways of ingenol angelate from Euphorbia peplus, ginkgolides from Ginkgo biloba, of dopaminergic diterpenoids from Vitex agnus-castus, and triptolide from T. wilfordii. Currently we are working on profiling the diterpenoid composition of all approx. 300 species of the Australian desert plant genus Eremophila and pathway elucidation of target diterpenoids based on their observed bioactivities. Several bioactive diterpenoids have been identified already.
Using combinatorial biochemistry, we have demonstrated the modular nature of terpenoids biosynthetic pathways, and we have been able to produce new to nature compounds.
Using the biosynthetic pathway of forskolin as a model system, and in collaboration with different groups, we have been able to heterologously produce diterpenoids using sunlight and photosynthetic energy, in host organisms like algae and cyanobacteria.
Using again forskolin as a model pathway, we have shown that b5 enzymes can contribute significantly in the efficiency of CYP-containing biosynthetic pathways (ongoing work).
Research Group web page