[P006] Poster

1:00 PM - 1:50 PM JST(4:00 AM - 4:50 AM UTC)

[P03-338] Enzymatic Synthesis and Comparative Study of α- and β-Anomeric Glycosides of 6-Gingerol: Impact on Solubility and Bioactivity

○Jiumn-Yih Wu¹, Tzi-Yuan Wang², Hsiou-Yu Ding³, Han-Ying Lin⁴, Te-Sheng Chang⁴ (1. National Quemoy University (Taiwan), 2. Academia Sinica (Taiwan), 3. Chia Nan University of Pharmacy and Science (Taiwan), 4. National University of Tainan (Taiwan))

Keywords:

Biotransformation,Anomeric Glycosides,Enzymatic Glycosylation,6-Gingerol,Solubility,Anti-inflammatory

6-Gingerol (6G), the primary bioactive component of ginger (Zingiber officinale), exhibits significant therapeutic potential, including anti-inflammatory, antioxidant, and anti-tumor properties. However, its application in pharmaceuticals and nutraceuticals is constrained by poor aqueous solubility, which is influenced by the length of its side chain. To address this, our study utilized a biotransformation platform involving glycoside hydrolases (GHs) and glycosyltransferases (GTs) to synthesize novel α- and β-anomeric glycosides of 6G, aiming to enhance its physicochemical and biological profiles.In the α-glycosylation pathway, the enzyme ArG (an α-glucosidase from Agrobacterium radiobacter DSM 30147) was uniquely effective among screened GHs. Utilizing maltose as an economical sugar donor, ArG catalyzed regioselective glycosylation at the C-5 hydroxyl group of the 6G side chain, yielding 6-gingerol-5-O-α-glucoside. This α-anomer achieved an aqueous solubility of 3,520 mg/L, a 5.5-fold increase over the aglycone (643 mg/L), and demonstrated a significantly enhanced antioxidant potency with an IC₅₀ of 15.3 μM, representing a 10-fold improvement compared to the parent 6G.Conversely, the β-glycosylation process, catalyzed by Bacillus-derived GTs (specifically BsUGT489) using UDP-glucose, resulted in a more diverse product profile. This complexity arises from the simultaneous occurrence of enzymatic catalysis at both the C-5 and C-4' positions and a chemical β-elimination reaction. Five distinct derivatives were identified, including the novel molecules 6-gingerol-5,4'-O-β-diglucoside and 6-gingerol-5-O-β-glucoside. Notably, 6-gingerol-5-O-β-glucoside exhibited the highest water solubility at 10,900 mg/L, while the diglucoside reached 14,900 mg/L. Furthermore, the study identified 6-shogaol-4'-O-β-glucoside as a highly potent anti-inflammatory agent with an IC₅₀ of 10.3 μM, the most effective among all glycosylated products.These results demonstrate that enzymatic anomeric glycosylation not only resolves the solubility limitations of 6-gingerol but also allows for the strategic modulation of its biological activities. The discovery of these novel glycosides, particularly the high-solubility β-anomers and the potent anti-inflammatory shogaol-glycoside, provides a valuable foundation for developing high-value ginger-based therapeutic agents.