Switching glycosyltransferase UGTBL1 regioselectivity toward polydatin synthesis using a semi-rational design.

The 62nd residue of glycosyltransferase UGTBL1 was identified as a "hotspot" for glycosylation at 3-OH of resveratrol. Via semi-rational design including structure-guided alanine scanning and saturation mutations, the mutation I62G significantly switched the regioselectivity from 4'-OH to 3-OH of resveratrol and mainly produced polydatin (87.7%), a therapeutic natural product.