A DES-assisted microbial transformation strategy integrating choline chloride/ethylene glycol-based deep eutectic solvent (DES) with Lactobacillus plantarum fermentation was developed to optimize isofraxidin yield from Acanthopanax senticosus. Systematically optimized parameters (pH 6.0, 25:1 mL/g liquid-solid ratio, 37 °C, 0.6 mol/L DES) achieved a 2.3-fold yield increase (0.274 mg/g) versus conventional methods. Multi-omics analysis suggested that DES treatment was associated with changes in glycoside hydrolase-related genes, phenylpropanoid-related pathways, and hydroxylation-related metabolic responses. Targeted metabolomics confirmed accelerated substrate-product conversion (42.5% lilacoside depletion, 2.3× isofraxidin accumulation). DES synergistically improved phytochemical mass transfer, enzymatic stability, and metabolic rewiring, establishing a sustainable framework for natural product biosynthesis via DES-biological hybrid systems.
Keywords: Biotransformation; deep eutectic solvent; metabolome; transcriptome.