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 <i>in vivo</i>. 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 <i>Glycine max</i> 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-<i>O</i>-glucosyltransferase Sbaic7OGT from <i>Scutellaria baicalensis</i> was selected as the most effective. As a result of the experiments conducted, eight <i>trans</i>-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 <i>cis</i>-chalcone glycosides. This study highlights the novel use of a cascade reaction involving Glycine max sucrose synthase (GmSuSy) for the efficient glycosylation of <i>trans</i>-4'-hydroxychalcones, alongside the unexpected discovery of <i>cis</i>-chalcone glycosides during the purification process.