Biomass-derived solvent engineering enhances whole-cell-catalyzed regioselective acylation of prim-O-glucosylcimifugin

Prim-O-glucosylcimifugin (POG) is a bioactive chromone C-glycoside whose pharmaceutical applicability is limited by its low lipophilicity. Structural modification through acylation provides a means of tuning the physicochemical properties of natural products. In this study, Aspergillus oryzae whole cells were used for the regioselective acylation of POG in biomass-derived solvent systems. Among the media tested, the tetrahydrofuran/diethyl carbonate (THF/DEC, 1:1, v/v) system gave the best catalytic performance, with an initial reaction rate of 22.20 mmol·L⁻¹ ·h⁻¹ , 99% conversion, and 99% 6′′-regioselectivity. Kinetic analysis showed that THF/DEC also gave the highest apparent catalytic efficiency (V max /K m ) of all the solvent systems tested. In THF/DEC, the whole-cell biocatalyst retained 95.94% of its initial activity after six consecutive cycles, compared with only 12.84% in pure THF. Under the optimized conditions, nine POG ester derivatives were synthesized, and their ClogP values increased systematically with acyl chain length. These results show that biomass-derived solvent systems can improve whole-cell catalytic performance and provide a practical route to lipophilic glycoside derivatives.