Abstract
Glycosylation, which is catalyzed by UDP-glycosyltransferases (UGTs), is an important biological modification for the structural and functional diversity of ginsenosides. In this study, the promiscuous UGT109A1 from Bacillus subtilis was used to synthesize unnatural ginsenosides from natural ginsenosides. UGT109A1 was heterologously expressed in Escherichia coli and then purified by Ni-NTA affinity chromatography. Ginsenosides Re, Rf, Rh1, and R1 were selected as the substrates to produce the corresponding derivatives by the recombinant UGT109A1. The results showed that UGT109A1 could transfer a glucosyl moiety to C3-OH of ginsenosides Re and R1, and C3-OH and C12-OH of ginsenosides Rf and Rh1, respectively, to produce unnatural ginsenosides 3,20-di-O-β-d-glucopyranosyl-6-O-[α-l-rhamnopyrano-(1→2)-β-d-glucopyranosyl]-dammar-24-ene-3β,6α,12β,20S-tetraol (1), 3,20-di-O-β-d-glucopyranosyl-6-O-[β-d-xylopyranosyl-(1→2)-β-d-glucopyranosyl]-dammar-24-ene-3β,6α,12β,20S-tetraol (6), 3-O-β-d-glucopyranosyl-6-O-[β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl]-dammar-24-ene-3β,6α,12β,20S-tetraol (3), 3,12-di-O-β-d-glucopyranosyl-6-O-[β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl]-dammar-24-ene-3β,6α,12β,20S-tetraol (2), 3,6-di-O-β-d-glucopyranosyl-dammar-24-ene-3β,6α,12β,20S-tetraol (5), and 3,6,12-tri-O-β-d-glucopyranosyl-dammar-24-ene-3β,6α,12β,20S-tetraol (4). Among the above products, 1, 2, 3, and 6 are new compounds. The maximal activity of UGT109A1 was achieved at the temperature of 40 °C, in the pH range of 8.0–10.0. The activity of UGT109A1 was considerably enhanced by Mg2+, Mn2+, and Ca2+, but was obviously reduced by Cu2+, Co2+, and Zn2+. The study demonstrated that UGT109A1 was effective in producing a series of unnatural ginsenosides through enzymatic reactions, which could pave a way to generate promising leads for new drug discovery.
Highlights
Ginseng (Panax ginseng Meyer) has been widely used in traditional herbal medicine for thousands of years in Asia [1]
Glycosylation, Glycosylation, which isprotopanaxadiol catalyzed by UDP-glycosyltransferase (UGT), plays an important which role inis catalyzed by UDP-glycosyltransferase (UGT), plays an important role in ginsenoside biosynthesis
Glycosylation catalyzed by UGTs is usually the last step of natural product biosynthesis, but it catalyzed by UGTs is usually last step of[28]
Summary
Ginseng (Panax ginseng Meyer) has been widely used in traditional herbal medicine for thousands of years in Asia [1]. Ginsenosides, the principal active constituents of ginseng, have demonstrated a wide spectrum of pharmacological activities, including antitumor, anti-oxidation, anti-aging, and anti-inflammatory effects, and so on [2,3,4,5,6]. Molecules2018, 22of of the tetracyclic triterpenoid aglycones, protopanaxadiol (PPD), and protopanaxatriol (PPT) [7]. Position, and type of sugar moieties attached to Variation in the position, andtheir type structural of sugar moieties attached to ginsenosides can markedly ginsenosides cannumber, markedly increase diversity, and lead to changes in their increase their structural diversity, and lead to changes in their bioactivities [8,9,10]. Bioactivities [8,9,10].
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