We are working on the dynamic assembly of biosynthetic enzyme complexes, termed metabolons, for the production of phytochemicals. Plants produce an immense number of bioactive compounds with potential for applications as pharmaceuticals, colorants and flavors. Despite of the chemical diversity of phytochemicals, their biosynthesis involves a highly modular assembly of specific enzyme classes such as oxidoreductases, cytochromes P450 and transferases. Assembly of metabolons facilitates direct transfer of substrates and intermediates between sequential enzymes, which results in increased flux devoid of concomitant release of toxic or labile intermediates. We are interested in understanding how plants assemble metabolons on-demand in response to environmental challenges.
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- Structural organizationWe are studying the structural organization of metabolons and their different configurations. We are interested in general mechanisms regulating the assembly of metabolons such as scaffolding proteins, protein-protein interactions and the local membrane environment.
- Dynamic assemblyWe are uncovering the dynamics of metabolon assembly at the single molecule level. The diffusion of individual enzymes and entire metabolons provides kinetic insight on the assembly and disassembly. In the process, we are developing new platforms for studying protein-protein interactions, membrane sorting and binding of soluble enzymes.
- Functional consequencesWe apply our findings to study the functional consequences of enzyme engineering and lipid composition on substrate channeling using in vivo and in vitro systems. As part of this research topic we are optimizing biomimetic membrane systems for studying multienzyme complexes.
- 2019-2024 The language of plant metabolic highways, Emerging Investigator Novo Nordisk Foundation (PI: Tomas Laursen)
- 2018-2022 Directing plant metabolism towards formation of high value bioactive products, Sapere Aude Starting Grant, Independent Research Fund Denmark (PI: Tomas Laursen)
- 2017-2019 Plant metabolon discovery, isolation and molecular characterization for optimizing metabolic highways, Postdoc Fellowship Novo Nordisk Foundation (PI: Tomas Laursen)
- Molecular snapshots of dynamic membrane-bound metabolons Bassard, J.E., Laursen, T.* (2019) Methods in Enzymology 617, 1-27
- Dynamic metabolic solutions to the sessile life style of plants Knudsen, C., Gallage, N.J., Hansen, C.C., Møller, B.L., Laursen, T.* (2018) Natural Product Reports 35()11, 1140-1155
- Direct observation of multiple conformational states in Cytochrome P450 oxidoreductase and their modulation by membrane environment and ionic strength Bavishi, K., Li, D., Eiersholt, S., Hooley, E., Petersen, T., Møller, B.L., Hatzakis, N.S.*, Laursen, T.* (2018) Scientific Reports, 8(1), 6817
- Controlling Styrene Maleic Acid Lipid Particles through RAFT Smith A.A.A., Autzen H.E., Laursen T., Wu V., Yen M., Hall A., Hansen SD., Cheng Y., Xu T. (2017) Biomacromolecules, 13;18(11), 3706-3713
- Characterization of a dynamic metabolon producing the defense compound dhurrin in sorghum Laursen, T., Borch, J., Knudsen, C., Bavishi, K., Torta, F., Martens, H.J., Silvestro, D., Hatzakis, N.S., Wenk, M.R., Dafforn, T.R., Olsen, C.E., Motawia, M.S., Hamberger, B., Møller, B.L., Bassard, J-E. (2016) Science 354(6314), 890-893
- Single molecule activity measurements of cytochrome P450 oxidoreductase reveal the existence of two discrete functional states Laursen, T.*, Singha, A.*, Rantzau, N., Tutkus, M., Borch, J., Hedegard, P., Stamou, D., Møller, B.L., Hatzakis, N.S. (2014) ACS Chemical Biology 9(3), 630-634
Our research group take an interdisciplinary basic science approach to elucidate fundamental mechanisms governing the plasticity of the biosynthesis of phytochemicals, which is well positioned between multiple groups at the Section for Plant biochemistry working on pathway discovery and heterologous production, including:
- Biochemical engineering (Sotirios Kampranis)
- Synthetic Biology (Birger Lindberg Møller)
- High-Value Phytochemicals (Irini Pateraki)
- Molecular Evolution of Specialized Metabolism (Søren Bak)
Our basic science approach will benefit from collaboration with additional internal groups with expertise in plant physiology and metabolomics, including:
- Plant Ecophysiology (Elisabeth Heather Neilson)
- Plant Metabolic plasticity (Nanna Bjarnholt)
We have established collaboration with world leading external experts, which provide access to state-of-the-art technologies and knowledge, including:
- Cryo Electron Microscopy (Bjørn Panyella Pedersen, Aarhus University, DK)
- Native Mass Spectrometry (Jonathan T. Hopper and Carol Robinson, Oxford University, UK)
- Neutron Reflectometry (Marité Cardenas, Malmö University, SE)
- SMALP technology (Timothy Dafforn, University of Birmingham, UK)
- Single Molecule Microscopy (Jay T. Groves, UC-Berkeley, USA and Nikos Hatzakis, University of Copenhagen, DK)
- Computational modeling (Flemming Jørgensen, University of Copenhagen, DK)