In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Xi Chen of the Department of Chemistry at the University of California-Davis will explore the development of chemoenzymatic synthesis and simple cartridge-purification methods for complex glycosphingolipids. The focus of the current project will be on neolacto-series glycosphingolipids with various lengths. While chemoenzymatic synthetic methods have been increasingly developed and used for producing oligosaccharides, less progress has been made in preparative-scale and large-scale synthesis of long and complex glycosphingolipids. This is mainly due to the limited access to suitable glycosyltransferases and sugar nucleotides as well as challenges in product purification.
This work combines highly efficient glycosyltransferase-based one-pot multienzyme glycosylation systems with facile cartridge-purification schemes to allow the synthesis of complex glycosphingolipids with high yield, low cost, and in a short period of time from inexpensive monosaccharides, common nucleotides, and other simple starting materials. The process can be adapted to automated synthesis of glycolipids. The easy accessibility of glycolipids will provide essential probes and standards for basic research and greatly facilitate the understanding of their important roles and accelerate their therapeutic applications as cancer vaccines, cancer markers, and antimicrobial treatment. The proposed chemoenzymatic synthetic approaches and cartridge purification scheme are sustainable, as they use bioregenerable catalysts, a minimal amount of chemical reagents and organic solvents, and are environmentally friendly. This project will provide training to graduate students, undergraduate students, and high school students of diverse economic, gender, cultural, and ethnic backgrounds, allowing them to gain valuable skills, independence, and confidence in interdisciplinary research.
