Seminar Title: Enzyme Discovery & Engineering to Create Suitable Biocatalysts

Speaker: Prof. Uwe T. Bornscheuer, Institute of Biochemistry, Dept. of Biotechnology & Enzyme Catalysis, University of Greifswald, Greifswald, Germany [website]

Abstract:

This lecture will cover recent achievements in the discovery, protein engineering and application of enzymes in biocatalysis [1]. For the asymmetric synthesis of chiral amines, we recently developed a sophisticated growth selection method and could create highly active and selective enzymes from three classes to make important chiral precursors for pharmaceutical building blocks [2]. We have engineered a P450 enzyme for the highly selective formation of ursodeoxycholic acid (UDCA) from lithocholic acid [3]. For the recycling of plastics, we have investigated PET [4], for which we determined the first structure of an MHETase in complex with a substrate analogue [5] and also provided important adjustments of a published PETase structure [6]. We also used various methods of protein engineering to improve several PET-hydrolase for higher activity and thermostability [7]. Most recently, we have identified the first urethanases in a metagenomic library able to degrade polyurethanes [8] and designed an enzyme cascade to degrade poly(vinylalcohols) [9]. Finally, we have explored the degradation of complex algal polysaccharides such as agar/porphyran [10] and ulvan [11] using a set of enzymes discovered in marine bacteria.

[1]      Yi., D. et al., Chem. Soc. Rev., 50, 8003-8049 (2021); Wu, S. et al. Angew. Chem. Int. Ed., 60, 88-119 (2021); Rudroff, F. et al., Nat. Catal. 1, 12-22 (2018); Badenhorst C.P.S., Bornscheuer, U.T., Trends Biochem. Sci., (2018), 43, 180-198; Bornscheuer, U.T. et al., Nature, 485, 185-194 (2012)

[2]      Wu, S. et al. Nature Commun., 13, 7458 (2022)

[3]      Grobe, S. et al., Angew. Chem. Int. Ed., 60, 753-757 (2021)

[4]      Wei, R. et al. (2022), ACS Catal., 12, 3382-3396 (2022); Wei, R. et al., Nature Catal., 3, 867-871 (2020); Bornscheuer, U.T., Science, 351, 1155-1156 (2016)

[5]      Palm, G.J. et al., Nature Commun., 10, 1717 (2019)

[6]      Wei, R. et al., Nature Commun., 10, 558 (2019)

[7]      Pfaff, L. et al., ACS Catal., 12, 9790-9800 (2022); von Haugwitz et al., ACS Catal., 12, 15259-15270 (2022)

[8]      Branson, Y. et al., Angew. Chem. Int. Ed., 62, e202216220 (2023)

[9]      von Haugwitz, G. et al., Angew. Chem. Int. Ed., 62, e202216962 (2023)

[10]    Reisky, L. et al., Nat. Chem. Biol., 14, 342-344 (2018); Robb, C.S. et al., Biochem. J., 475, 3875-3886 (2018); Brott, S. et al., ChemBioChem, 23, e202200269 (2022); Brott, S. et al., Appl. Microb. Biotechnol., 107, 2363-2384 (2023).

[11]    Reisky, L. et al., Nat. Chem. Biol., 15, 803-812 (2019) Bäumgen, M. et al., J. Biol. Chem., 297, 101210 (2021).