Predictive Production of a New Highly Soluble Glucoside, Corylin-7-O-β-Glucoside with Potent Anti-inflammatory and Anti-melanoma Activities.

Abstract

Computational tools can now facilitate screening precursors and selecting suitable biotransformation enzymes for producing new bioactive compounds. This study applied the data-mining approach to screen for candidate precursors of glycosyltransferases to produce new glucosides from 412 commercial natural compounds. Among five candidates, experimental results showed that only corylin could be glycosylated by the bacterial glycosyltransferase, BsUGT489. Analysis of interaction potential between candidates and glycosyltransferase by molecular docking tools also found that corylin was the only compatible substrate. The new glucoside was purified and confirmed to be corylin-7-O-β-glucoside. The aqueous solubility of corylin-7-O-β-glucoside was 14.2 times more than its precursor aglycone, corylin. Corylin-7-O-β-glucoside retained anti-inflammatory activity in lipopolysaccharide-induced nitric oxide production of murine macrophage RAW 264.7 cells, with an IC₅₀ value of 121.1 ± 9.5 µM. Further, corylin-7-O-β-glucoside exhibited more potent anti-melanoma activity against murine B16 and human A2058 melanoma cells than corylin. Together, predictive studies facilitate the production of a new glucoside, corylin-7-O-β-glucoside, which is highly soluble and possesses anti-inflammatory and anti-melanoma activities and therefore has promising future applications in pharmacology.