S-Glycosides chemo-enzymatic synthesis

Two strategies are currently developed in the group to biocatalyze the synthesis of S-glycosides, using a sugar donor, and a sulfur-containing acceptor:

  • Glycosidases mutated in their active site that can potentially act as thioglycoligases.
  • S-Glycosyltransferases , only enzymes that synthesize S-glycosides found in Nature.

 

  • Thioglycoligases

Mutation of the catalytic acid/base residue in glycosidases can sometimes lead to a new enzymatic activity. These mutants can catalyze the formation of S-glycosidc bond using thiol instead of alcohol as a sugar acceptor. Our group aim to identify new potential thioglycoligases, as well as to understand the molecular mechanism underlying this reaction.

These thioglycoligases can then serve as efficient and useful biocatalysts to synthesize a broad range of S-glycosides that can be later used in cosmetics or therapeutics.

 

  • S-Glycosyltransferases

Glucosinolates are plant metabolites that have long been of interest to human society because of their role in flavor and taste of Brassicaceae vegetables or condiments. A critical part of their biosynthesis is catalyzed by a rare enzyme: S-glucosyltransferases, such as UGT74B1. This enzyme can catalyze the formation of an original glycosidic C-S bond, instead of C-O, or C-N bonds usually found in glycoconjugates.

The purpose of this project is to study some of plant S-UGT, and understand their mechanism and structure. They will eventually be used as biocatalysts for the synthesis of original S-glycosides, not related to the natural glucosinolates. This collaborative project combines the expertises of several research groups: organic synthesis in Pr. Tatibouët group (ICOA), Structural biology in Pr. Oulyadi group (Univ. Rouen) and biochemistry and enzymology in our group.

 

Industrial partner :

Glycodiag

Funding :

Région Centre –GLYCOPEPS Project

Conseil Général 45 –GlycoCosm Project

 

For more information:

Is the acid/base catalytic residue mutation in β-d-mannosidase DtMan from Dictyoglomus thermophilum sufficient enough to provide thioglycoligase activity?

L. Guillotin, N. Richet, P. Lafite, R. Daniellou

Biochimie, 2017

UGT74B1 from Arabidopsis thaliana as a versatile biocatalyst for the synthesis of desulfoglycosinolates

S. Marroun, S. Montaut, S. marques, P. Lafite, G. Coadou, P. Rollin, G. Jousset, M. Schuler, A. Tatibouet, H. Oulyadi, R. Daniellou

Org. Biomol. Chem., 2016

Chapter 10: Enzymatic thioglycosylation: current knowledge and challenges

L. Guillotin, P. Lafite, R. Daniellou

in RSC Carbohydrate Chemistry: Volume 40, 2014