| Summary: | Resveratrol is a natural polyphenol with antioxidant activity and numerous health benefits. However, in vivo application of this compound is still a challenge due to its poor aqueous solubility and rapid metabolism, which leads to an extremely low bioavailability in the target tissues. In this work, rXynSOS-E236G glycosynthase, designed from a GH10 endoxylanase of the fungus <i>Talaromyces amestolkiae,</i> was used to glycosylate resveratrol by using xylobiosyl-fluoride as a sugar donor. The major product from this reaction was identified by NMR as 3-<i>O</i>-ꞵ-<span style="font-variant: small-caps;">d</span>-xylobiosyl resveratrol, together with other glycosides produced in a lower amount as 4′-<i>O</i>-ꞵ-<span style="font-variant: small-caps;">d</span>-xylobiosyl resveratrol and 3-<i>O</i>-ꞵ-<span style="font-variant: small-caps;">d</span>-xylotetraosyl resveratrol. The application of response surface methodology made it possible to optimize the reaction, producing 35% of 3-<i>O</i>-ꞵ-<span style="font-variant: small-caps;">d</span>-xylobiosyl resveratrol. Since other minor glycosides are obtained in addition to this compound, the transformation of the phenolic substrate amounted to 70%. Xylobiosylation decreased the antioxidant capacity of resveratrol by 2.21-fold, but, in return, produced a staggering 4,866-fold improvement in solubility, facilitating the delivery of large amounts of the molecule and its transit to the colon. A preliminary study has also shown that the colonic microbiota is capable of releasing resveratrol from 3-<i>O</i>-ꞵ-<span style="font-variant: small-caps;">d</span>-xylobiosyl resveratrol. These results support the potential of mutagenic variants of glycosyl hydrolases to synthesize highly soluble resveratrol glycosides, which could, in turn, improve the bioavailability and bioactive properties of this polyphenol.
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