CAREER: Harnessing enzymes in novel synthesis of complex carbohydrates

本项目致力于开发一种新的化学-酶合成复杂碳水化合物的方法。这种非常规的方法在获得结构明确的复杂寡糖和多糖方面特别有用。在单糖底物中形成糖苷键的活性酶将被招募来作用于双糖底物。这种化学反应将被用于合成低聚糖和含有非末端唾液酸残基的多糖以及结构明确的肝素/硫酸肝素。酶催化反应（如醛缩酶催化反应）也将在教育方面得到利用，在本科课程（化学和生物专业，包括医学预科学生）中引入协调的讲座和实验内容。与类似的非酶有机反应的比较将作为进一步讨论的跳板。通过ACS项目SEED计划，经济困难的高中学生将被介绍到跨学科研究的广阔图景。在有机和大分子化学项目CAREER奖的支持下，加州大学戴维斯分校化学系的陈曦教授正在探索合成复杂多糖（糖）的新方法。陈教授正在开发一种新的化学-酶合成方法来获得这些难以通过常规化学和酶合成获得的结构。通过利用一些酶对其作用的分子的灵活性，陈教授能够招募这些酶来产生比自然设计的更复杂的产物。获得这些复杂的产物对于我们理解许多生物和生化过程至关重要，在这些过程中，多糖起着关键作用，包括细胞识别和粘附现象。考虑到酶催化有机反应的方法也将被带到本科讲座和实验室项目中，并与非酶过程进行比较，为学生讨论和学习提供了一个有趣的平台。经济困难的高中学生将通过ACS项目SEED计划了解跨学科研究的广阔图景。

This project addresses the development of a novel chemo-enzymatic method for the synthesis of complex carbohydrates. This unconventional method is especially useful in obtaining structurally defined complex oligosaccharides and polysaccharides. Enzymes active in the formation of glycosidic linkages from monosaccharide substrates will be recruited to act upon disaccharide substrates. This chemistry will be exploited for the synthesis of oligosaccharides and polysaccharides containing non-terminal sialic acid residues and structurally defined heparin/heparan sulfate. Enzyme-catalyzed reactions (e.g. aldolase-catalyzed reactions) will be exploited on the educational front as well, introducing coordinated lecture and laboratory content to the undergraduate curricula (for both chemistry and biology majors, including premedical students). Comparisons with similar non-enzymatic organic reactions will serve as a springboard for additional discussions. Through the ACS Project SEED program, economically disadvantaged high school students will be introduced to the broad picture of interdisciplinary research. With the support of this CAREER award from the Organic and Macromolecular Chemistry Program, Professor Xi Chen, of the Department of Chemistry at the University of California at Davis, is exploring new methods for the synthesis of complex polysaccharides (sugars). Professor Chen is developing a novel chemo-enzymatic synthetic method to obtain these structures, which are difficult to obtain through conventional chemical and enzymatic synthesis. By taking advantage of the flexibility of some enzymes with regards to the molecules upon which they act, Professor Chen is able to recruit these enzymes to produce more complex products than those they were designed by Nature to produce. Access to these complex products is essential for development of our understanding of the numerous biological and biochemical processes in which polysaccharides play key roles, including cellular recognition and adhesion phenomena. Consideration of the methods by which enzymes catalyze organic reactions will also be brought to the undergraduate lecture and laboratory programs, with comparisons with non-enzymatic processes providing an interesting platform for student discussion and learning. Economically disadvantaged high school students will be introduced to the broad picture of interdisciplinary research through the ACS Project SEED program.