A Redox‐Controlled Substrate Engineering Strategy for Site‐Specific Enzymatic Fucosylation

Fucosylation is one of the most common modifications of oligo‐N‐acetyllactosamine (oligo‐LacNAc) glycans. However, none of known fucosyltransferases (FucTs) could install the α1,3‐linked fucose to the oligo‐LacNAc substrates in a site‐specific manner. Here, we report a facile and general redox‐contr...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-12, Vol.61 (50), p.e202211032-n/a
Main Authors: Lu, Na, Li, Yun, Xia, Hui, Zhong, Kan, Jia, Chenning, Ye, Jinfeng, Liu, Xianwei, Liu, Chang‐Cheng, Cao, Hongzhi
Format: Article
Language:English
Subjects:
Aldehydes
Fucose
fucosylation
Fucosyltransferases - genetics
Fucosyltransferases - metabolism
Galactose
Galactose oxidase
glycoside
Glycosylation
oligo-LacNAc glycans
Oxidation
Oxidation-Reduction
Polysaccharides
Substrate Specificity
Substrates
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Summary:Fucosylation is one of the most common modifications of oligo‐N‐acetyllactosamine (oligo‐LacNAc) glycans. However, none of known fucosyltransferases (FucTs) could install the α1,3‐linked fucose to the oligo‐LacNAc substrates in a site‐specific manner. Here, we report a facile and general redox‐controlled substrate engineering strategy for the site‐specific α1,3‐fucosylation of complex glycans containing multiple LacNAc units. This strategy takes advantage of an operationally simple oxidation enzyme module by using galactose oxidase (GOase) to convert the LacNAc unit into oxidized C6′‐aldehyde LacNAc sequence, which is not a good substrate for recombinant α1,3‐FucT from Helicobacter pylori strain 26695 (Hpα1,3FucT), enabling the site‐specific α1,3‐fucosylation at intact LacNAc sites. The general applicability and robustness of this strategy were demonstrated by the synthesis of a variety of structurally well‐defined fucosides of linear and branched O‐ and N‐linked glycans. A galactose oxidase‐mediated redox system was coupled with enzymatic modular assembly strategy to control the site‐selectivity of α1,3‐fucosylation. This redox‐controlled site‐specific fucosylation strategy provides a general and operational simple approach for the precisely enzymatic synthesis of various complex fucosylated oligo‐N‐acetyllactosamine (oligo‐LacNAc) containing O‐ and N‐glycans with defined fucosylation patterns.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202211032