Presentation Information
[1ENZ-07-KL]Enzyme Discovery and Engineering to Create Biocatalysts Suitable for Organic Synthesis and Beyond
○Uwe Bornscheuer1 (1. University of Greifswald, Institute of Biochemistry (Germany))
Keywords:
Biocatalysis,Organic Synthesis,Enzyme Engineering,Plastic recycling
This lecture will cover achievements in the discovery, protein engineering and application of enzymes in biocatalysis [1].
Examples for the creation of enzymes for biocatalytic applications include the asymmetric synthesis of chiral amines for which we discovered and improved (S)-selective amine transaminases for the acceptance of bulky ketones [2]. Later, we used machine learning tools to expand their substrate scope and enhance their activity [3]. We also 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 [4].
The introduction and removal of protecting groups under mild reaction conditions and with desired selectivities is important for organic synthesis. Very recently, we could show that so-called unspecific peroxygenases (UPO) can be highly specific in the removal of methyl, ethyl or even allyl protecting groups from a variety of compounds [5].
To address the global problem of plastic waste, we have performed extensive research for the recycling of PET, for which we have improved different esterases [6] and established a protocol enabling a comparison of PETases reported in literature [7]. We also designed an enzyme cascade to degrade poly(vinylalcohols) [8] and for low molecular weight polyethylene [19].
Recently, we have identified the first urethanases in a metagenomic library able to degrade polyurethanes, solved their X-ray structures, performed biochemical characterization and could broaden the substrate scope [10].
[1] Bayer, T. et al., Angew. Chem. Int. Ed., 64, e202505976 (2025); Buller, R. et al., Science, 382, eadh8615 (2023); Yi., D. et al., Chem. Soc. Rev., 50, 8003-8049 (2021); Wu, S. et al. Angew. Chem. Int. Ed., 60, 88-119 (2021); 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] Pavlidis, I. et al., Nature Chem., 8, 1076-1082 (2016).
[3] Weigmann, K.F.G. et al., ACS Catal., 15, 15121-15131 (2025); Menke, M.J. et al., ACS Catal., 14, 6462-6469 (2025); Ao, Y.F. et al., Angew. Chem. Int. Ed., 62, e202301660 (2023).
[4] Wu, S. et al. Nature Commun., 13, 7458 (2022).
[5] Csechala, L.A. et al. ACS Catal., 15, 17090-17100 (2025).[6] Wei, R. et al., Nature Catal., 3, 867-871 (2020); Bornscheuer, U.T. Science, 351, 1155-1156 (2016); R. Wei et al., Nature Commun., 10, 558 (2019).
[7] Arnal, G. et al., ACS Catal., 13, 13156-13166 (2023).
[8] von Haugwitz, G. et al., Angew. Chem. Int. Ed., 62, e202216962 (2023).
[9] Oiffer, T. et al., Angew. Chem. Int. Ed., 63, e202415012 (2024).
[10] Branson, Y. et al., Angew. Chem. Int. Ed., 62, e202216220 (2023); Bayer, T., et al., Angew. Chem. Int. Ed., 63, e202404492 (2024); Rotilio, L. et al. Angew. Chem. Int. Ed., 64, e202419535 (2025); Li, Z. et al., Adv. Sci., 12, 2416019 (2025)
Examples for the creation of enzymes for biocatalytic applications include the asymmetric synthesis of chiral amines for which we discovered and improved (S)-selective amine transaminases for the acceptance of bulky ketones [2]. Later, we used machine learning tools to expand their substrate scope and enhance their activity [3]. We also 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 [4].
The introduction and removal of protecting groups under mild reaction conditions and with desired selectivities is important for organic synthesis. Very recently, we could show that so-called unspecific peroxygenases (UPO) can be highly specific in the removal of methyl, ethyl or even allyl protecting groups from a variety of compounds [5].
To address the global problem of plastic waste, we have performed extensive research for the recycling of PET, for which we have improved different esterases [6] and established a protocol enabling a comparison of PETases reported in literature [7]. We also designed an enzyme cascade to degrade poly(vinylalcohols) [8] and for low molecular weight polyethylene [19].
Recently, we have identified the first urethanases in a metagenomic library able to degrade polyurethanes, solved their X-ray structures, performed biochemical characterization and could broaden the substrate scope [10].
[1] Bayer, T. et al., Angew. Chem. Int. Ed., 64, e202505976 (2025); Buller, R. et al., Science, 382, eadh8615 (2023); Yi., D. et al., Chem. Soc. Rev., 50, 8003-8049 (2021); Wu, S. et al. Angew. Chem. Int. Ed., 60, 88-119 (2021); 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] Pavlidis, I. et al., Nature Chem., 8, 1076-1082 (2016).
[3] Weigmann, K.F.G. et al., ACS Catal., 15, 15121-15131 (2025); Menke, M.J. et al., ACS Catal., 14, 6462-6469 (2025); Ao, Y.F. et al., Angew. Chem. Int. Ed., 62, e202301660 (2023).
[4] Wu, S. et al. Nature Commun., 13, 7458 (2022).
[5] Csechala, L.A. et al. ACS Catal., 15, 17090-17100 (2025).[6] Wei, R. et al., Nature Catal., 3, 867-871 (2020); Bornscheuer, U.T. Science, 351, 1155-1156 (2016); R. Wei et al., Nature Commun., 10, 558 (2019).
[7] Arnal, G. et al., ACS Catal., 13, 13156-13166 (2023).
[8] von Haugwitz, G. et al., Angew. Chem. Int. Ed., 62, e202216962 (2023).
[9] Oiffer, T. et al., Angew. Chem. Int. Ed., 63, e202415012 (2024).
[10] Branson, Y. et al., Angew. Chem. Int. Ed., 62, e202216220 (2023); Bayer, T., et al., Angew. Chem. Int. Ed., 63, e202404492 (2024); Rotilio, L. et al. Angew. Chem. Int. Ed., 64, e202419535 (2025); Li, Z. et al., Adv. Sci., 12, 2416019 (2025)
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