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

Abstract

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.

Structure–function relationship of terpenoid glycosyltransferases from plants

“…To date, only a few classes of potential substrates, in particular flavonoids, and their respective UGTs have been functionally characterized in detail. 5,34 This lack of insight is also largely due to hundreds of UGT-encoding genes in most plant species 10,11 and their substrate promiscuity. 24,35…”

Directed Evolution of a Plant Glycosyltransferase for Chemo- and Regioselective Glycosylation of Pharmaceutically Significant Flavonoids

“…Although a wealth of structural and biochemical information of UGTs has been reported, they are generally characterized by high chemo- and regioselectivity and stringent substrate specificity or promiscuous substrate specificity but poor chemo- and regioselectivity. This severely hindered their applications in the targeted synthesis of specific glycosides. − For example, in 2019, it was reported that the substrate scope of known flavonoid 3- O -glycosyltransferases is narrow and that their chemo- and regioselectivities are suboptimal . In another GT study, a structural comparison between the O -glycosyltransferase LanGT2 and the C -glycosyltransferase GTS8Ac was made. , In this mechanistic study, the effect of a remote mutation on the total enzyme conformation was reported, while the reshaping of the binding pocket was not aimed for.…”

The Fungal, Nutritional, and Metabolomic Diagnostics of the Oil Palm Elaeis guineensis Affected by Bud Rot Disease in Esmeraldas, Ecuador

“…Flavones, a subclassification of flavonoids, had also been identified in the present study, such as isoorientin and isovitexin, which are described as C-glycosyl flavonoids and are found in different plants [ 78 ]. Flavones have a variety of functions for the plant defense mechanism, similar to flavonoids, including interactions between species like resistance to pathogens, symbiosis, protection against herbivory, and allelopathy [ 79 , 80 ].…”