Glycosylation through C-glycosidic linkage is a specialized feature of chemical structure found in small molecules (e.g., natural products, nucleosides) and macromolecules (e.g., pseudouridine in RNA, protein C-mannosylation). Due to their resistance to hydrolysis, small molecule C-glycosides attract interest in medicinal chemistry, as exemplified by the antidiabetic drug dapagliflozin (an aryl C-β-glucoside). In this talk, I briefly review the synthesis of C-glucosides of (poly)phenolic acceptors by sugar nucleotide-dependent glycosyltransferases. Main focus is on enzymatic strategies to degrade these C-glycosides [1]. Deglycosylation is shown to involve oxidation and elimination. Recent studies suggest a four-step pathway (oxidation-elimination-hydration-reduction) to achieve net hydrolysis of both O- and C-glycosides. The functional pathway appears to be distributed broadly in microorganisms [1].
Reference:
[1] Johannes Bitter, Martin Pfeiffer, Annika J.E. Borg, Kirill Kuhlmann, Tea Pavkov-Keller, Pedro A Sánchez-Murcia, Bernd Nidetzky, Enzymatic β-elimination in natural product O- and C-glycoside deglycosylation. Nat. Commun. 14, 7123 (2023). https://doi.org/10.1038/s41467-023-42750-0.
Bernd Nidetzky is Full Professor of Biotechnology at Graz University of Technology (TU Graz) in Austria. At TU Graz, he is Head of the Institute of Biotechnology and Biochemical Engineering. There, he also serves as Head of TU Graz Field of Expertise in Human & Biotechnology. Since 2014, he is Scientific Director (CSO) of acib (Austrian Centre of Industrial Biotechnology), the major Austrian institution for collaborative research between academia and industry in industrial biotechnology focused on bioproduction. Bernd Nidetzky is an engineer in chemistry by training from TU Graz, with specialisation in biochemistry and biotechnology. He holds a doctoral degree in engineering (biotechnology) also from TU Graz. After about 10 years at the University of Natural Resources and Life Sciences (BOKU) in Vienna where he received a Habilitation in Biotechnology and Enzymology, Nidetzky joined TU Graz in 2002 for his current academic position. The main research theme of Bernd Nidetzky is enzymes of carbohydrate processing. The research covers mechanistic and applied aspects of the enzymes, to a similar degree and always in depth. Nidetzky is interested in the biochemical engineering sciences promoting the successful use of the enzymes in industrial processes.
