Research progress of C-glycosyltransferases for natural products

C-Glycosyltransferases (CGTs) are natural biocatalyst responsible for the formation of C-glycosides, transferring sugar moieties from activated nucleotide sugar donors to acceptor substrates and establishing C-C glycosidic bonds. C-glycosides show diverse pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, and antitumor activities, and comparing with O-glycosides, C-glycosides exhibit better pharmacological properties due to their glycosidic bonds being more resistant to chemical and biological degradation. Thus, CGTs have shown considerable potential in drug research and development. Although research on CGTs has made significant progress, with respect to the number of identified CCTs and the understanding of catalytic mechanism, there is still a large distance between CGTs and extensively studied O-glycosyltransferases (OGTs). The reported crystal structures of CGTs have provided a good elucidation of the recognition of sugar donors. However, the limited acceptor-bound structure hinders the comprehensive understanding of their catalytic mechanisms, thereby affecting the application in the fields of bioengineering and pharmaceuticals. Here we summarize the information of identified CGTs for natural product regarding substrate types, protein structures, proposed catalytic mechanisms, and CGT-related engineering and applications, aiming to bring out some new ideas for future research and development.