Computational Insights into the Selectivity of Lipases in the (−)-Epigallocatechin Gallate (EGCG) Esterification Reaction Based on Molecular Docking

The lipase-catalyzed esterification reaction of (-)-epigallocatechin gallate (EGCG) is an effective method to improve its lipophilicity. However, the determinants of EGCG and acyl donors influencing the selectivity of EGCG esterification sites catalyzed by lipases have rarely been systematically investigated. In this study, molecular docking was used to predict the binding modes of EGCG with the catalytic pockets of lipases and acyl-lipases to reveal the selectivity of EGCG esterification sites at the molecular level. Acetylated EGCG was also synthesized, and its structure was analyzed using liquid chromatography-mass spectrometry (LC-MS). The docking results showed that compared with lipases, acyl-lipases were more accurate models for analyzing the EGCG esterification sites selectivity. Under conditions of the affinity ≤-5 kcal/mol and minimum D1 value (the distance between the H atom on the Nε of His imidazole group in catalytic triad and the hydroxyl O atom of EGCG), acyl-lipases showed a clear preference for the hydroxyl groups on the D-ring of EGCG. LC-MS results suggested that the substitution sites of monoacetylated EGCG were the hydroxyl groups on the D-ring of EGCG. This study indicated that the binding modes of acyl-lipases with EGCG could predict the selectivity of EGCG esterification sites catalyzed by lipases.