Enzymatic Glycosylation of 4'-Hydroxychalcones: Expanding the Scope of Nature's Catalytic Potential

Chalcones, including 4'-hydroxychalcones, have garnered significant attention in the area of drug discovery due to their diverse pharmacological properties, such as anti-inflammatory, antioxidative, and anticancer effects. However, their low water solubility and bioavailability limit their efficacy in vivo. Glycosylation presents a promising approach to enhance the water solubility, stability, and metabolic properties of chalcones. This study investigates the enzymatic glycosylation of eight chemically synthesized 4'-hydroxychalcones using a diverse set of sugar glucosyltransferases from bacterial, plant, and fungal sources, alongside Glycine max sucrose synthase (GmSuSy) in a cascade reaction. Among the tested enzymes, five exhibited a remarkable versatility for glycoside production, and for large-scale biotransformation, flavonoid 7-O-glucosyltransferase Sbaic7OGT from Scutellaria baicalensis was selected as the most effective. As a result of the experiments conducted, eight trans-chalcone glycosides were obtained. During the purification of the reaction products, we also observed the isomerization of the products by simple sunlight exposure, which resulted in eight additional cis-chalcone glycosides. This study highlights the novel use of a cascade reaction involving Glycine max sucrose synthase (GmSuSy) for the efficient glycosylation of trans-4'-hydroxychalcones, alongside the unexpected discovery of cis-chalcone glycosides during the purification process.