Enzymatic rutinosylation of phenolic compounds by 6-O-α-rhamnosyl-β-glucosidase from Sarocladium strictum and evaluation of their antitumoral effects

GONZALEZ A; WEIZ G; MOLEJON MI; BRECCIA J

Congreso; Biotrans2021; 2021

α-L-rhamnosyl-β-D-glucosidases are diglycosidases that catalyze the cleavage of theglycosidic bond between the aglycone and the disaccharide rutinose (α-L-rhamnopyranosyl-(1→6)-β-D- glucopyranose) of specific flavonoid glycosides [1]. Some α-L-rhamnosyl-β-D-glucosidases exhibit transglycosylation activities which provide an approach for obtainingnovel rutinosylated molecules with enhanced capacities. These rutinosides could exhibitnovel biological and biomedical activities [2]. Specifically, the presence of rhamnose asterminal unit of the rutinosides can change the pharmacokinetic properties of compounds astherapeutic agents [3]. Rhamnose-capped molecules appear to be resistant to hydrolysis inhuman tissues due to the absence of endogenous rutinosidases and α-L- rhamnosidaseswhich would normally hydrolyze the respective glycosidic bonds. Thus, the rhamnose-capped molecules target specifically the sites where L-rhamnose receptors are located. Thisis an interesting strategy for enhancing the antitumoral effects of drugs [4]. We have recently described a new α-L-rhamnosyl-β-D-glucosidases from the fungusSarocladium strictum DMci 093557. Regarding substrate scope the enzyme hydrolyzed 7-O-β-rutinosyl- and 3-O-β-rutinosyl- flavonoids. The enzyme also exhibited transglycosylationactivities, transferring rutinose (6-O-α-L-rhamnosyl-β-D-glucose) from rutin onto a broadspectrum of alcoholic acceptors, primary, secondary and phenolic alcohols. Remarkably, therutinosylation of short chains length alcohols as acceptor (methanol, ethanol) was notdetected and phenolic acceptors such as resveratrol, 4-methylumbelliferone, resorcinol andphloroglucinol, were rutinosylated with reasonable yields. Moreover, the synthesis ofrutinosides of phenolic compounds were optimized and their antitumoral effects weresuccessfully tested in liver cancer cell lines and compared with the respective aglycone.