Improvement of the pharmacological activity of menthol via enzymatic β-anomer-selective glycosylation.

Menthol has a considerable cooling effect, but the use range of menthol is limited because of its extremely low solubility in water and inherent flavor. (-)-Menthol β-glucoside was determined to be more soluble in water (>27 times) than (-)-menthol α-glucoside; hence, β-anomer-selective glucosylation of menthol is necessary. The in vitro glycosylation of (-)-menthol by uridine diphosphate glycosyltransferase (BLC) from Bacillus licheniformis generated (-)-menthol β-glucoside and new (-)-menthol β-galactoside and (-)-menthol N-acetylglucosamine. The maximum conversion rate of menthol to (-)-menthol β-D-glucoside by BLC was found to be 58.9%. Importantly, (-)-menthol β-D-glucoside had a higher cooling effect and no flavor compared with menthol. In addition, (-)-menthol β-D-glucoside was determined to be a non-sensitizer in a skin allergy test in the human cell line activation test, whereas menthol was a sensitizer.