Highly regioselective biotransformation of ginsenoside Rg1 to 25-OH derivatives of 20(S/R)-Rh1 by Cordyceps Sinensis

Abstract

25-OH ginsenosides are potent and rare prodrugs in natural sources. However current strategies for such modification always end up in undesirable side products and unsatisfied yield that hinders them from further applications. Herein, ginsenoside Rg1 was thoroughly converted into 20(S/R)-Rh1 and 25-OH-20(S/R)-Rh1 by Cordyceps Sinensis in an optimum medium. The chemical correctness of either 25-OH-20(S/R)-Rh1 epimers was validated by LC-IT-TOF-MSn and ¹³C NMR spectrometry. The biocatalytic pathway was established as Rg1 → 20(S/R)-Rh1 → 25-OH-20(S/R)-Rh1. The molar bioconversion rate for total 25-OH-20(S/R)-Rh1 was calculated to be 82.5%, of which S-configuration accounted for 43.2% while R-configuration 39.3%. These two 25-OH derivatives are direct hydration products from 20(S/R)-Rh1 without other side metabolites, suggesting this is a highly regioselective process. In conclusion, this biocatalytic system could be harnessed to facilitate the preparation of diversified 25-OH ginsenosides with high yields of the target compound and simple chemical background in the reaction mixture.

Keywords: 25-OH derivative; Deglycosylation; Ginsenoside Rg1; Hydration; Microbial biotransformation.