11023-94-2Relevant articles and documents
Leloir glycosyltransferases and natural product glycosylation: Biocatalytic synthesis of the C-glucoside nothofagin, a major antioxidant of redbush herbal tea
Bungaruang, Linda,Gutmann, Alexander,Nidetzky, Bernd
, p. 2757 - 2763 (2013)
Nothofagin is a major antioxidant of redbush herbal tea and represents a class of bioactive flavonoid-like C-glycosidic natural products. We developed an efficient enzymatic synthesis of nothofagin based on a one-pot coupled glycosyltransferasecatalyzed transformation that involves perfectly selective 3′-C-β-D-glucosylation of naturally abundant phloretin and applies sucrose as expedient glucosyl donor. C-Glucosyltransferase from Oryza sativa (rice) was used for phloretin C-glucosylation from uridine 5'-diphosphate (UDP)-glucose, which was supplied continuously in situ through conversion of sucrose and UDP catalyzed by sucrose synthase from Glycine max (soybean). In an evaluation of thermodynamic, kinetic, and stability parameters of the coupled enzymatic reactions, poor water solubility of the phloretin acceptor substrate was revealed as a major bottleneck of conversion efficiency. Using periodic feed of phloretin controlled by reaction progress, nothofagin concentrations (45 mM; 20 gL-1) were obtained that vastly exceed the phloretin solubility limit (5-10 mM). The intermediate UDP-glucose was produced from catalytic amounts of UDP (1.0 mM) and was thus recycled 45 times in the process. Benchmarked against comparable glycosyltransferase-catalyzed transformations (e.g., on quercetin), the synthesis of nothofagin has achieved intensification in glycosidic product formation by up to three orders of magnitude (μM → mM range). It thus makes a strong case for the application of Leloir glycosyltransferases in biocatalytic syntheses of glycosylated natural products as fine chemicals.
Functional Characterization and Structural Basis of an Efficient Di-C-glycosyltransferase from Glycyrrhiza glabra
Chi, Chang-Biao,He, Jun-Bin,Li, Fu-Dong,Li, Kai,Liu, Zhen-Ming,Ma, Ming,Qiao, Xue,Shi, Xiao-Meng,Su, Hui-Fei,Wang, Yu-Xi,Wang, Zi-Long,Yang, Dong-Hui,Ye, Min,Yun, Cai-Hong,Zhang, Liang-Ren,Zhang, Meng,Zhang, Zhi-Yong,Zhang, Zhong-Yi
supporting information, p. 3506 - 3512 (2020/03/06)
A highly efficient di-C-glycosyltransferase GgCGT was discovered from the medicinal plant Glycyrrhiza glabra. GgCGT catalyzes a two-step di-C-glycosylation of flopropione-containing substrates with conversion rates of >98%. To elucidate the catalytic mech
Targeting type 2 diabetes with c-glucosyl dihydrochalcones as selective sodium glucose co-transporter 2 (sglt2) inhibitors: Synthesis and biological evaluation
Jesus, Ana R.,Vila-Vi?osa, Diogo,Machuqueiro, Miguel,Marques, Ana P.,Dore, Timothy M.,Rauter, Amélia P.
, p. 568 - 579 (2017/02/05)
Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC50 = 9.23 nM) were considerably weaker inhibitors of SGLT1 (IC50 = 10.19 μM). They showed no effect on the sodium independent GLUT family of glucose transporters, and the most potent ones were not acutely toxic to cultured cells. The interaction of a C-glucosyl dihydrochalcone with a POPC membrane was modeled computationally, providing evidence that it is not a pan-assay interference compound. These results point toward the discovery of structures that are potent and highly selective inhibitors of SGLT2.
