Enzymatic Synthesis of Resveratrol α-Glycosides from β-Cyclodextrin-Resveratrol Complex in Water

Abstract

Although resveratrol (3,5,4′-trihydroxy-stilbene) is one of the most studied natural product because of its biological properties such as antioxidant or anticancer, its low water solubility and stability (influenced by pH, light and increased temperature), as well as its propensity to oligomerize, limit its bioavailability and applications in nutraceutic, cosmetics or pharmaceutical industries. Besides, resveratrol production at the multigram scale through vine cell culture is limited by the tedious extraction of pure resveratrol from the bioconversion medium due to its complexation by cyclodextrins, the latter being used as elicitors in the bioproduction process. In this work, we have been able to overcome all these drawbacks by performing a single organic solvent-free enzymatic α-glycosylation directly from the βcyclodextrin-resveratrol complex in water using β-cyclodextrin as glycoside-donor. The combined effects of five parameters (CGTase amount, cyclodextrin amount, cyclodextrin/resveratrol ratio, pH, and temperature) were studied by design of experiments (DoE) to maximize the glycosylation yield. The optimal setting point of parameters was obtained by response surface methodology (RSM). After optimization, an efficient α-glycosylation was performed being obtained 35% of molar yield. The major glycosidestwo monoglycosides: 3-O-α-D-glucosyl-resveratrol and 4′-O-α-D-glucosyl-resveratrol and two diglycosides: 3-O-α-D-maltosyl-resveratrol and 4′-O-α-D-maltosyl-resveratrolwere characterized using a hyphenated liquid chromatography-solid phase extraction-nuclear magnetic resonance system, then separated and purified using centrifugal partition chromatography (CPC). Their antiradical properties, as well as that of their crude mixture, were evaluated through DPPH analysis. Results confirmed that the position 4′−OH is the best position for the glycosylation to maintain the highest antiradical properties.

Enzymatic Synthesis of a Novel Pterostilbene α-Glucoside by the Combination of Cyclodextrin Glucanotransferase and Amyloglucosidase

“…(Toruzyme 3.0L) worked better than that from Bacillus macerans (CGTase Amano). The transglycosylation activity of CGTase is well reported, as it is able to glucosylate other phenolic compounds such as resveratrol [ 26 , 27 ], catechin [ 28 ], hydroquinone [ 29 ], kaempferol [ 30 ] or genistein [ 31 ].…”

Resveratrol Functionalized Carboxymethyl-β-Cyclodextrin: Synthesis, Characterization, and Photostability

“…e previous article focused on the study of the transformation of transresveratrol into the cis under UV irradiation [34]. e reason of this change was that resveratrol was an unstable polyphenol which was easily damaged by UV irradiation [19,35]. In addition, comparable results were obtained when resveratrol formed inclusion complex with CM-β-CD.…”

“…For example, a new approach to the stabilization of resveratrol is its O-glycosylation technology. Recently, Marié's group demonstrated the authentically successful O-glycosylation of trans-resveratrol to overcome its low water solubility and stability by enzymatic synthesis of resveratrol α-glycosides from β-cyclodextrin-resveratrol complex in water [19]. Torres's group reported the synthesis of a series of α-glucosyl derivatives of resveratrol by a trans-glycosylation reaction catalyzed by the enzyme cyclodextrin glucanotransferase (CGTase) using starch as glucosyl donor [20].…”

Optimization of Regioselective α-Glucosylation of Hesperetin Catalyzed by Cyclodextrin Glucanotransferase

“…(Toruzyme 3.0L) [ 30 , 33 ], employing partially hydrolyzed starch (maltodextrins with DP ≤ 60) as glucosyl donor. This enzyme has demonstrated an extraordinary ability to glucosylate other mono- and polyphenolic compounds [ 26 , 31 , 32 , 34 , 35 , 36 , 37 , 38 ].…”