Relevance: While the EU has committed to becoming the world’s first climate-neutral continent by 2050, almost 70% of its gross available energy is currently still obtained from fossil fuels. Therefore, the EU aims to replace fossil fuels with renewable alternatives.
A promising sustainable alternative is obtaining bioenergy from lignocellulosic biomass waste, which can be upcycled into biofuels, biochemicals, and other bioproducts.  However, this is only possible if the decomposition of the recalcitrant lignocellulose becomes more efficient.
Overall topic: Transition to a green society may be facilitated by a recently discovered family of metalloenzymes called lytic polysaccharide monooxygenases (LPMOs): LPMOs have shown to significantly boost the degradation of several polysaccharides, among them the major components of lignocellulose.  Very recently, it was also shown that LPMOs are highly relevant for food secu-rity: a study in Science  showed that LPMOs are key players in the two most destructive fungal crop diseases in the world (rice blast and grey mold). This project will concern the elucidation of the LPMO mechanism, employing advanced electronic structure methods.
Goals and methods: Intriguingly, the reaction mechanism of LPMOs has remained elusive, alt-hough this mechanism is essential to unfold the full industrial potential of LPMOs. However, exper-imental and methodological limitations have complicated mechanistic studies.  Another complica-tion is the continuous discovery of new LPMOs: Currently, eight LPMO families (AA9-AA11, AA13-AA17) have been classified, displaying remarkably diverse substrate specificities, regioselectivities, and active site compositions.  Yet, very few LPMO families have been investigated with theoreti-cal methods. Thus, it is unknown if different families employ the same or different mechanisms.
My group investigates the LPMO mechanism with quantum mechanics (QM) as well as with QM combined with molecular mechanics (QM/MM) . We mainly employ DFT as the QM method, but we also develop and employ multiconfigurational methods . Our hypothesis in this project is that the LPMO mechanism has remained elusive because existing theoretical studies considered too few LPMO families and lacked an accurate theoretical methodology. The project will therefore de-velop new electronic structure methods for metalloproteins. We will employ these methods for LPMO families whose mechanism has not been scrutinized by theoretical methods. The project offers training in advanced multiconfigurational methods as well as polarizable embedding QM/MM models.
The project is supervised by Associate Prof. Erik D. Hedegård (EDH) at the University of Southern Denmark (SDU). The project is designed to enable the candidate to become an innovative and in-dependent researcher in the field of theoretical bio-inorganic chemistry.
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 (a) Vaaje-Kolstad, G., et. al. (2010). Science, 330, 219. (b) Harris, P. V., et. al. (2010). Bioche-mistry, 49, 3305. (c) Johansen, K. S. (2016). Biochem. Soc. Trans., 44, 143. (d) Ipsen, J. Ø., et. al. (2021). Biochem. Soc. Trans., 49, 531.
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 (a) Hedegård, E. D., Ryde, U. (2018). Chem. Sci., 9, 3866. (b) McEvoy, A et al. (2021). Chem. Sci. 12, 352.
 (a) Larsson, E. D. et al. (2020). Dalton Trans., 49, 1501. (b) Hedegård, E. D. et al. (2018). J. Chem. Phys. 148, 214103.
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