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Extending the Structural Diversity of α‐Flavonoid Glycosides with Engineered Glucansucrases
Author(s) -
Malbert Yannick,
PizzutSerin Sandra,
Massou Stéphane,
Cambon Emmanuelle,
Laguerre Sandrine,
Monsan Pierre,
Lefoulon François,
Morel Sandrine,
André Isabelle,
RemaudSimeon Magali
Publication year - 2014
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201402144
Subject(s) - chemistry , flavonoid , luteolin , glycosylation , combinatorial chemistry , bioavailability , mutant , stereochemistry , docking (animal) , biochemistry , biology , antioxidant , bioinformatics , gene , medicine , nursing
Flavonoids constitute an important class of bioactive molecules, the physicochemical properties of which can be modulated by glucosylation. A structurally guided approach has been used to isolate glucansucrases modified in their acceptor‐binding site and specialized for luteolin glucosylation. Of a small‐size library, we isolate mutants showing up to an 8‐fold increase in flavonoid conversion rate over that observed with the parental enzyme. Di‐ and triglucosylated luteolin derivatives never described before have been obtained. They exhibit 282‐ and 17 708‐fold increases in water solubility, respectively, and are protected from oxidation by the glucosylation reaction. Molecular docking enables insight into the product specificity of the best mutants. These results demonstrate that α‐transglucosylase engineering is a powerful means to generate highly specific catalysts for flavonoid glucosylation and deliver new structural scaffolds with increased bioavailability and high relevance for therapeutic applications.