CAREER: Meshing Synthesis and Biosynthesis in Research and Teaching

这个CAREER项目的研究部分探讨了代表性的真核生物，原核生物和超嗜热（生长在80摄氏度以上）古菌之间的差异，在他们利用糖，更具体地说，他们的进化策略底物识别和营业额参与碳水化合物聚合物和糖核苷酸的合成酶。了解三种主要生命形式之间碳水化合物结合和催化的差异不仅提供了一个窗口，了解生命的基本方面如糖代谢的进化，而且还提供了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温度范围内定向进化和使用这些蛋白质催化剂的线索。该项目的教学内容是：1）重新设计本科有机实验室课程，以进行基于发现的学习，并引入最先进的概念和技术; 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物理有机化学课程，并从与化学交叉的领域开发实例。探索生命的三个主要分支之间带电糖识别的差异和开发新的教具将在吸引学生学习化学、指导和培训学生进行研究、开发新的基于质谱的合成方法、发现基于可再生资源的合成中最佳使用碳水化合物识别生物催化剂的规则方面产生广泛的影响，该奖项由代谢生物化学项目和有机与大分子化学项目共同资助。

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.