Enzymatic Synthesis of Acylphloroglucinol 3‐C‐Glucosides from 2‐O‐Glucosides using a C‐Glycosyltransferase from Mangifera indica

Chen, Fan; Sun, Lili; Chen, Ridao; Xie, Kebo; Yang, Lin; Dai, Jungui

doi:10.1002/chem.201600411

Cited by 24 publications

(33 citation statements)

References 50 publications

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“…To our knowledge, most known CGTs exhibit relatively narrow substrate promiscuity . Although two benzophenone CGTs, MiCGT and MiCGTb from M. indica , could accept a variety of substrates, the majority of them feature a 2,4,6‐trihydroxybenzophenone‐like structure fragment . Thus, TcCGT1 exhibits broader substrate promiscuity than previously reported CGTs.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the known CGTs exhibit relatively low substrate promiscuity and poor catalytic efficiency, which limit their application in the synthesis of structurally diverse C ‐glycosides. MiCGT from Mangifera indica can accept a variety of natural and unnatural substrates, but majority of them feature a 2,4,6‐trihydroxybenzophenone‐like core structure . Thus, it is critical to mine novel CGTs with catalytic promiscuity to improve the structural diversity of natural products for drug discovery.…”

Section: Introductionmentioning

confidence: 99%

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Molecular and Structural Characterization of a Promiscuous C‐Glycosyltransferase from Trollius chinensis

et al. 2019

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Herein, the catalytic promiscuity of TcCGT1, a new C‐glycosyltransferase (CGT) from the medicinal plant Trollius chinensis is explored. TcCGT1 could efficiently and regio‐specifically catalyze the 8‐C‐glycosylation of 36 flavones and other flavonoids and could also catalyze the O‐glycosylation of diverse phenolics. The crystal structure of TcCGT1 in complex with uridine diphosphate was determined at 1.85 Å resolution. Molecular docking revealed a new model for the catalytic mechanism of TcCGT1, which is initiated by the spontaneous deprotonation of the substrate. The spacious binding pocket explains the substrate promiscuity, and the binding pose of the substrate determines C‐ or O‐glycosylation activity. Site‐directed mutagenesis at two residues (I94E and G284K) switched C‐ to O‐glycosylation. TcCGT1 is the first plant CGT with a crystal structure and the first flavone 8‐C‐glycosyltransferase described. This provides a basis for designing efficient glycosylation biocatalysts.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular and Structural Characterization of a Promiscuous C‐Glycosyltransferase from Trollius chinensis

et al. 2019

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“…Over the past decade, 44 CGTs related to flavonoids and xanthonoids have been identified from different plant species (Brazier‐Hicks et al, 2009; Falcone Ferreyra et al, 2013; Nagatomo et al, 2014; Chen et al, 2015, 2016; Hirade et al, 2015; Sasaki et al, 2015; Ito et al, 2017; Wang et al, 2017; He et al, 2019; Mashima et al, 2019; Ren et al, 2020; Sun et al, 2020; Zhang et al, 2020). However, taking the numerous C ‐glycosides and their derivatives into consideration, the number of CGTs identified is still very limited, especially for CGTs involved in the biosynthesis of di‐ C ‐glycosides.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic basis for stepwise C‐glycosylation in the formation of flavonoid di‐C‐glycosides in sacred lotus (Nelumbo nucifera Gaertn.)

Feng

Taguchi

et al. 2021

The Plant Journal

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Lotus plumule, the embryo of the seed of the sacred lotus (Nelumbo nucifera), contains a high accumulation of secondary metabolites including flavonoids and possesses important pharmaceutical value. Flavonoid Cglycosides, which accumulate exclusively in lotus plumule, have attracted considerable attention in recent decades due to their unique chemical structure and special bioactivities. As well as mono-C-glycosides, lotus plumule also accumulates various kinds of di-C-glycosides by mechanisms which are as yet unclear. In this study we identified two C-glycosyltransferase (CGT) genes by mining sacred lotus genome data and provide in vitro and in planta evidence that these two enzymes (NnCGT1 and NnCGT2, also designated as UGT708N1 and UGT708N2, respectively) exhibit CGT activity. Recombinant UGT708N1 and UGT708N2 can C-glycosylate 2-hydroxyflavanones and 2-hydroxynaringenin C-glucoside, forming flavone mono-C-glycosides and di-C-glycosides, respectively, after dehydration. In addition, the above reactions were successfully catalysed by cell-free extracts from tobacco leaves transiently expressing NnCGT1 or NnCGT2. Finally, enzyme assays using cell-free extracts of lotus plumule suggested that flavone di-C-glycosides (vicenin-1, vicenin-3, schaftoside and isoschaftoside) are biosynthesized through sequentially C-glucosylating and Carabinosylating/C-xylosylating 2-hydroxynaringenin. Taken together, our results provide novel insights into the biosynthesis of flavonoid di-C-glycosides by proposing a new biosynthetic pathway for flavone C-glycosides in N. nucifera and identifying a novel uridine diphosphate-glycosyltransferase (UGT708N2) that specifically catalyses the second glycsosylation, C-arabinosylating and C-xylosylating 2-hydroxynaringenin Cglucoside.

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“…The conserved His residue acts as a proton acceptor under the assistance of a nearby Asp residue. The deprotonated sugar acceptor directly attacks the sugar donor and the precise positioning of the sugar acceptor is proposed to determine the formation of C–C or C–O glycosidic bond 35, 58–60. To develop CGTs from the existing OGTs by protein engineering, minimal active‐site remodeling was performed on OsCGT from O. sativa and PcOGT from Pyrus communis .…”

Section: Protein Engineering Of Flavonoidc‐glycosyltransferasesmentioning

confidence: 99%

FlavonoidC‐Glycosyltransferases: Function, Evolutionary Relationship, Catalytic Mechanism and Protein Engineering

Dai

Chen

et al. 2021

ChemBioEng Reviews

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C‐glycosylflavonoids are polyphenolic phytochemicals that are ubiquitously distributed in the plant kingdom and confer a wealth of health‐promoting benefits to human body. These compounds harbor one or more sugar moieties that are attached to various regions of the flavonoid scaffold through rigid C–C glycosidic bonds. The diverse structures of C‐glycosylflavonoids are granted by the prominent reactions of flavonoid C‐glycosyltransferases (CGTs). This review gives an extensive overview of CGTs that are involved in the biosynthesis of C‐glycosylflavonoids, focusing on their evolutionary relationship and substrate specificity. Furthermore, structural insights into the catalytic mechanism and protein engineering of flavonoid CGTs are summarized. This review provides an important guidance for identification of novel flavonoid CGTs, biosynthesis of C‐glycosylflavonoids, and elucidation of the function‐structure relationship of flavonoid CGTs.

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Enzymatic Synthesis of Acylphloroglucinol 3‐C‐Glucosides from 2‐O‐Glucosides using a C‐Glycosyltransferase from Mangifera indica

Cited by 24 publications

References 50 publications

Molecular and Structural Characterization of a Promiscuous C‐Glycosyltransferase from Trollius chinensis

Molecular and Structural Characterization of a Promiscuous C‐Glycosyltransferase from Trollius chinensis

Enzymatic basis for stepwise C‐glycosylation in the formation of flavonoid di‐C‐glycosides in sacred lotus (Nelumbo nucifera Gaertn.)

FlavonoidC‐Glycosyltransferases: Function, Evolutionary Relationship, Catalytic Mechanism and Protein Engineering

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