SusChEM: Chemoenzymatic Methods for Efficient Synthesis of Glycolipids

在本研究计划中，加州大学戴维斯分校化学系陈Xi教授将探索复杂鞘糖脂的化学酶法合成和简单的分离纯化方法。本项目的重点是不同长度的新乳糖系列鞘糖脂。虽然化学酶促合成方法已越来越多地被开发和用于生产寡糖，但在长且复杂的鞘糖脂的酶促和大规模合成方面进展较少。这主要是由于获得合适的糖基转移酶和糖核苷酸的途径有限以及产品纯化方面的挑战。 这项工作结合了高效的糖基转移酶为基础的一锅多酶糖基化系统与简易的酶解纯化方案，以允许合成复杂的鞘糖脂高产率，低成本，并在短时间内从廉价的单糖，常见的核苷酸，和其他简单的起始材料。该方法可适用于糖脂的自动化合成。糖脂的易得性将为基础研究提供必要的探针和标准，极大地促进对其重要作用的理解，并加速其作为癌症疫苗、癌症标记物和抗菌治疗的治疗应用。提出的化学酶合成方法和柱纯化方案是可持续的，因为它们使用生物可再生催化剂、最少量的化学试剂和有机溶剂，并且对环境友好。该项目将为不同经济，性别，文化和种族背景的研究生，本科生和高中生提供培训，使他们获得跨学科研究的宝贵技能，独立性和信心。

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.