CAREER: Meshing Synthesis and Biosynthesis in Research and Teaching

这一职业项目的研究部分探索了具有代表性的真核生物、原核生物和高温(生长在80摄氏度以上)古生菌在利用糖方面的差异，更具体地说，探索了参与合成碳水化合物聚合物和糖核苷酸的酶对底物识别和周转的进化策略。了解三种主要生命形式之间在碳水化合物结合和催化方面的差异不仅为了解糖代谢这一生命的基本方面的进化提供了一个窗口，而且还为这些蛋白质催化剂在实验室和工业合成碳水化合物或碳水化合物衍生结构的一系列温度下的定向进化和使用提供了线索。这个项目的教学部分是：1)重新设计基于发现的学习的本科有机实验室课程，并引入最新的概念和技术；2)将生物结合事件常见的非共价相互作用纳入本科有机化学和研究生水平的物理有机化学课程，并从与化学交叉的领域开发实例。广泛的影响：探索生活的三个主要分支在识别带电糖类方面的差异，开发新的教学辅助工具，将对吸引学生学习化学，指导和培训学生的研究，开发基于质谱学的新方法和合成方法产生广泛影响，发现碳水化合物识别生物催化剂在基于可再生资源的合成中的最佳使用规则，并对生命的基本过程如何进化提供见解。该奖项由新陈代谢生物化学计划和有机与高分子化学计划共同资助。

The research component of this CAREER project explores the differences between a representative eukaryote, prokaryote, and hyperthermophilic (grows at over 80 degrees C) archaea in their utilization of sugars and, more specifically, their evolved strategies for substrate recognition and turnover by enzymes involved in the synthesis of carbohydrate polymers and sugar nucleotides. An understanding of the differences in carbohydrate binding and catalysis between the three major life forms provides not only a window into the evolution of such a fundamental aspect of life as sugar metabolism, but also clues to the directed evolution and use of these protein catalysts over a range of temperatures for laboratory and industrial syntheses of carbohydrate or carbohydrate-derived structures. The teaching component of this project is 1) redesigning the undergraduate organic laboratory curriculum for discovery-based learning and introducing state-of-the-art concepts and techniques and 2) incorporating the non-covalent interactions common to biological binding events into and developing examples from fields intersecting with chemistry for both undergraduate organic chemistry and graduate level physical organic chemistry courses.Broader Impact: Probing the differences in charged sugar recognition among the three major branches of life and developing new teaching aids will have broad impact in attracting students to chemistry, in mentoring and training students in research, in developing new mass spectrometry-based and synthetic methodologies, in discovering rules for best use of carbohydrate-recognizing biocatalysts in syntheses based on renewable resources, and in providing insights into how the basic processes of life may have evolved.This award is co-funded by the Metabolic Biochemistry program and the Organic and Macromolecular Chemistry program.