Discovery and heterologous expression of cyclodextrin glycosyltransferases and their application in natural product modification: A review

Cyclodextrin glycosyltransferase (CGTase) (EC 2.4.1.19), a member of glycoside hydrolase family 13, is primarily utilized for producing cyclodextrins. The demand for enzymes with superior properties has driven the continuous discovery and identification of novel CGTases. However, native CGTases often encounter challenges related to low expression levels in their original organisms. To meet industrial demands, heterologous expression and optimization of CGTases have been implemented to achieve high-level production. This review summarizes recent advances and provides perspectives for future research on the discovery of novel CGTases from diverse sources, as well as optimization strategies for their heterologous expression in various hosts. Furthermore, considering that many natural products contain sugar moieties, CGTases have been utilized to improve their properties through transglycosylation. We also discuss the application of CGTases in enhancing the water solubility, bioactivity, and flavor of natural products.