Tomas Laursen

Current research

Our research group, Dynamic Metabolons, are working on the plasticity of biosynthetic membrane protein 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 glycosyltransferases. Formation of enzyme complexes, metabolons, facilitate direct transfer of substrates and intermediates between sequential enzymes, which results in increased flux and avoid release of toxic or labile intermediates. In order to produce phytochemicals in heterologous hosts it is imperative to understand the mechanisms facilitating the organization of biosynthetic metabolons and their dynamic nature

Projects

• Elucidate key enzymes and lipids involved in stabilizing metabolons for biosynthesis of cyanogenic glucosides and diterpenoids
• Elucdate the structure of biosynthetic metabolons
• Single molecule behavior of cytochrome P450 oxidoreductase

Student projects available

• Guiding metabolism through binding of small molecule drugs
• Protein Design for Plant Metabolite Diversity

Major Collaborations

Most of the research conducted is highly interdisciplinary, which is why I am fortunate to have established both new and long-lasting collaborations with experts in several fields.

Associate Professor Nikos Hatzakis - Single Molecule Microscopy/Spectroscopy - Dept. of Chemistry, University of Copenhagen, DK

Associate Professor Marite Cardenas - Neutron Reflectometry - Malmö University, SE

Assistent Professor Bjørn Panyella Pedersen - Cryo Electron Microscopy - Dept. of Molecular Biology and Genetics, Aarhus University, DK

Professor Timothy Dafforn - SMALP technology - School of Biosciences, University of Birmingham, UK

Funding

2018-2022     The Danish Council for Independent Research - Sapere Aude Starting Grant

2017-2019     Novo Nordisk Foundation Postdoc fellowship

2015-2017     VILLUM Foundation Postdoc Fellowship

2013               The Danish Council for Independent Research - EliteForsk travelgrant

Links

https://plen.ku.dk/english/research/plant_biochemistry/dynamic-metabolons/

http://plantplasticity.ku.dk/research/enzymes/

http://plantplasticity.ku.dk/research/supramolecules/

http://synbio.ku.dk/researchers/tomas-laursen/

Selected Publications

1. Knudsen, C.,Gallage, N.J., Hansen, C.C., Møller, B.L., Laursen, T. "Dynamic metabolic solutions the sessile life style of plants". Nat. Prod. Rep. 2018, 35(11), 1140-1155
2. Bavishi, K., Li, D., Eiersholt, S., Hooley, E., Petersen, T., Møller, B.L., Hatzakis, N.S., Laursen, T. "Direct observation of multiple conformational states in Cytochrome P450 oxidoreductase and their modulation by membrane environment and ionic strength". Scientific Reports 2018, 8(1), 6817
3. Laursen T., Stonebloom S.H., Pidatala V.R., Birdseye D.S., Clausen M.H., Mortimer J.C., Scheller H.V. "Bifunctional glycosyltransferases catalyze both extension and termination of pectic galactan oligosaccharides." The Plant Journal 2018, 94(2), 340-351
4. Smith A.A.A., Autzen H.E., Laursen T., Wu V., Yen M., Hall A., Hansen SD., Cheng Y., Xu T. “Controlling Styrene Maleic Acid Lipid Particles through RAFT”. Biomacromolecules. 2017, 13;18(11), 3706-3713
5. 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. “Characterization of a dynamic metabolon producing the defense compound dhurrin in sorghum”. Science 2016, 354(6314), 890-893
6. Laursen, T., Møller, B.L., Bassard, J-E. “Plasticity of specialized plant metabolism as mediated by dynamic metabolons”. Trends Plant Sci. 2015, 20(1), 20–32
7. Laursen, T., Singha, A., Rantzau, N., Tutkus, M., Borch, J., Hedegard, P., Stamou, D., Møller, B.L., Hatzakis, N.S. “Single Molecule Activity Measurements of Cytochrome P450 Oxidoreductase Reveal the Existence of Two Discrete Functional States”. ACS Chem. Biol. 2014, 9(3), 630-634
8. Wadsater, M., Laursen, T., Singha, A., Hatzakis, N.S., Stamou, D., Barker, R., Mortensen, K., Feidenhans'l, R., Møller, B.L., Cardenas, M. “Monitoring Shifts in the Conformation Equilibrium of the Membrane Protein Cytochrome P450 Reductase (POR) in Nanodiscs”. J. Biol. Chem. 2012, 287(41), 34596-34603