Plant Glycosides and Glycosidases: A Treasure-Trove for Therapeutics

Abstract

Plants contain numerous glycoconjugates that are metabolized by specific glucosyltransferases and hydrolyzed by specific glycosidases, some also catalyzing synthetic transglycosylation reactions. The documented value of plant-derived glycoconjugates to beneficially modulate metabolism is first addressed. Next, focus is given to glycosidases, the central theme of the review. The therapeutic value of plant glycosidases is discussed as well as the present production in plant platforms of therapeutic human glycosidases used in enzyme replacement therapies. The increasing knowledge on glycosidases, including structure and catalytic mechanism, is described. The novel insights have allowed the design of functionalized highly specific suicide inhibitors of glycosidases. These so-called activity-based probes allow unprecedented visualization of glycosidases cross-species. Here, special attention is paid on the use of such probes in plant science that promote the discovery of novel enzymes and the identification of potential therapeutic inhibitors and chaperones.

Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity

“…Sugar moiety has also been highlighted as the reason for previously confirmed stronger antifungal effect of apigenin-7O-glycoside compared to its aglycone apigenin [12]. This superiority might be related to increased solubility and amphiphilicity recorded for glycosylated plant metabolites, which may enhance their membrane transport [24].…”

Structure-based enzyme engineering improves donor-substrate recognition of Arabidopsis thaliana glycosyltransferases

“…Uridine diphosphate GTs have shown promising potential as catalysts in the synthesis of medically relevant glycosides [ 5 ]. However, incomplete understanding at the molecular level due to insufficient biochemical and structural information has hindered potential applications of most of these UGTs.…”

“…UDP activated sugars act as donors in the glycosylation reaction with UDP-glucose (UDP-Glc) serving as the primary sugar donor, followed by UDP-galactose (UDP-Gal), UDP-rhamnose, UDP-xylose, and UDP-glucuronic acid, respectively [ 4 ]. Furthermore, plant-derived natural products, as therapeutics of human health are of considerable interest to pharmaceutical industry [ 5 ]. For example, the planet-produced enzymes like ELELYSO (Protalix BioTherapeutics), is central to the production of lysosomal human GBA enzyme in carrot cells.…”

“…For example, the planet-produced enzymes like ELELYSO (Protalix BioTherapeutics), is central to the production of lysosomal human GBA enzyme in carrot cells. Another human lysosomal hydrolase is α-galactosidase A, used for treating Fabry disease [ 5 ]. As of today, there are a total of 122 Arabidopsis thaliana UGT genes, which are grouped into 14 phylogenetic groups A-N ( Supplementary Figure S1 ) [ 6 ].…”

In-vitro Evaluation of the Trypanocidal Activity of Andrographis paniculata Against Trypanosoma brucei brucei

“…Some cardioactive glycosides have been shown to exhibit activity in cough suppression (anti-tussive) and are very toxic thereby limiting their wide spread use. 16 Terpenoids/sterols were present in the ethanol and dichloromethane extracts but absent in the ethyl acetate fraction. The bioactive constituents of the A. paniculata can be attributed to its terpenoids with higher concentration and potent activity.…”