Programmable Enzymatic Toolbox for the Assembly of Fucosylated Chondroitin Derivatives

Fucosylated chondroitin sulfate (FuCS), a unique glycosaminoglycan derived from the body walls of sea cucumbers, plays a vital role in various physiological processes. Although the physiological importance of FuCS is well-documented, the biosynthesis pathway, especially α1–3 fucosylation, is still unclear, thus hindering the development of an enzymatic synthesis approach to access both it and its derivatives. Herein, we report a programmable enzymatic toolbox for the synthesis of fucosylated chondroitin derivatives. Two distinct microbial α1–3-fucosyltransferases were identified for the synthesis of fucosylated chondroitin. Through precise control over chondroitin backbone extension and fucosylation, 13 fucosylated chondroitin oligosaccharides were assembled. Additionally, the synthetic toolbox has been further adapted for the fucosylation of chondroitin sulfate A, setting the stage for the formulation of a FuCS glycan library. This work demonstrates a possible biosynthetic pathway of FuCS and paves the way for the synthesis of this intriguing biomolecule.