Biocatalytic Application of a Membrane‐Bound Coumarin C‐Glucosyltransferase in the Synthesis of Coumarin and Benzofuran C‐Glucosides

Abstract

A number of plant C‐glycosyltransferases (CGTs) have been recently identified, whereas the coumarin CGTs have not been found. Here we reported the first identification of a coumarin C‐glucosyltransferase MaCGT from Morus alba. The whole‐cell biocatalyst harboring MaCGT was exploited and exhibited strictly and efficiently regio‐ and stereo‐specific C‐glucosylation capacity toward structurally different coumarins. The whole‐cell of MaCGT was further applied to chemo‐enzymatically synthesize benzofuran C‐glucosides. Moreover, MaCGT is reported as the first characterized membrane‐bound CGT from plants, although sequence homology search has shown other potentially membrane‐bound CGTs from M. notabilis; and the presence of the transmembrane domain is critical for its catalytic activity and stability as demonstrated by the C‐glucosylation activity of truncated MaCGT proteins. In addition, the key residues involved in the C‐glucosylation of MaCGT were explored. These findings suggest the diversity of CGTs in the plant kingdom and demonstrate the significant potential of biocatalytic approach to produce structurally diverse C‐glycosides for drug discovery.

A double responsive fluorescent platform for sensing heavy metal ions based on a dual-emitting fluorescent covalent organic framework hydrogel film

“…Compared with other dyes, coumarin and its derivatives exhibit excellent photophysical properties and superior chemical stability, 18 and are extensively employed in various disciplines, including medicine, biology and sensing. [19][20][21][22] However, as far as we know, COF materials modified with coumarin dyes have not been reported.…”

Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica

“…Since the first experimental validation of a CGT (OsCGT, UGT72B1 ) in Oryza sativa ssp. indica, numerous key CGTs involved in the synthesis of C- glycosyl flavonoids, xanthone C- glycosides, and coumarin C- glycosides have been verified in plants ( Brazier-Hicks et al., 2009 ; Wang et al., 2020 ; Chen et al., 2021 ; Uchida et al., 2021 ). The formation process of these C- glycosides can be roughly divided into two steps.…”

“…In contrast, in Hypericum perforatum , the xanthone skeleton is directly C- glycosylated to form C- glycoside xanthone, and N4CGT1 and N4CGT2 directly catalyze the C- 4 glycosylation of norathyriol to form isomangiferin ( Uchida et al., 2021 ). In Morus alba and Angelica decursiva , MaCGT and AbCGT , respectively, are involved in C- glycoside coumarin biosynthesis ( Chen et al., 2021 ; Wang et al., 2022 ).…”

A Comprehensive Review on Benzofuran Synthesis Featuring Innovative and Catalytic Strategies

“…Besides the discovery of plant-based C -glycosyltransferase, recently coumarin-based C -glycosyltransferases have also been found. These coumarin C -glycosyltransferases 127 have been employed for the synthesis of benzofuran derivatives by Chen et al in 2021 . First, they carried out the total synthesis of coumarin C -glycosyltransferase by adding d -glucose and utilizing MACGT as a (whole cell) biocatalyst.…”

“…These coumarin C -glycosyltransferases 127 have been employed for the synthesis of benzofuran derivatives by Chen et al in 2021. 115 First, they carried out the total synthesis of coumarin C -glycosyltransferase by adding d -glucose and utilizing MACGT as a (whole cell) biocatalyst. Then, the synthesized coumarin C -glycosidase was cyclized in the presence of sodium hydroxide followed by subsequent acidification to achieve two novel carboxylic acid substituted benzofuran derivatives 128 and 129 ( Scheme 40 ).…”