CAREER: Integrating Chemical Biology into Research and Education: Studying Glycosylation of Cellulolytic Enzymes

凭借这一奖项，化学学部的生命过程化学项目资助了科罗拉多大学博尔德分校的谭仲平博士，研究纤维素酶的糖基化。纤维素酶是一类重要的酶，广泛用于工业生产来自可再生生物材料的燃料（生物燃料）。为了降低生产生物燃料的成本，提高纤维素酶和糖基化（即碳水化合物附着在蛋白质上）的性能是至关重要的，这似乎是实现这一任务的有希望的方法。提出的研究旨在建立糖基化和纤维素酶性能之间的联系，并为开发更有效的纤维素酶提供明确的指导方针。通过这个项目，学生将获得化学和生物领域的各种技能和经验。该项目包括计划教育中小学科学教师如何生产可再生生物燃料。通过化学合成、酶促生物转化和生化表征的结合，本研究项目旨在揭示纤维素酶糖基化的分子水平影响。提出的方法将使用化学和酶合成来制备均匀的糖基化蛋白异构体（糖型）库，控制占据的糖基化位点的数量和聚糖组成。糖基化对稳定性和功能的影响将通过比较这些定义良好的糖型阵列的特征来量化。预计这种类型的系统知识不仅能阐明糖基化在工业上重要酶的可能作用，而且还能导致纤维素酶糖变异体的识别，相对于目前在工业过程中使用的那些，效率更高。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Zhongping Tan from the University of Colorado at Boulder to investigate the glycosylation of cellulases, a class of important enzymes that are widely used in industry for the production of fuels derived from renewable biological materials (biofuels). In order to reduce the costs of producing biofuels, it is paramount to enhance the performance of cellulases and glycosylation, i.e., the attachment of carbohydrates to proteins, appears to be a promising way to achieve such a task. The proposed research seeks to establish a link between glycosylation and cellulase performance and provide clear guidelines to develop more efficient cellulase enzymes. By working on this project, students will gain a diverse range of skills and experiences across chemistry and biology. This project includes plans to educate elementary and secondary school science teachers on the production of renewable biofuels. Through the combined use of chemical synthesis, enzymatic biotransformation, and biochemical characterization, this research project seeks to unveil the molecular level impact of cellulase glycosylation. The proposed approach will use both chemical and enzymatic synthesis to prepare a library of homogeneous glycosylated protein isoforms (glycoforms) with control of the number of occupied glycosylation sites and of glycan composition. The effects of glycosylation on stability and function will be quantified by comparing the characteristics across these well defined glycoform arrays. This type of systematic knowledge is anticipated to not only shed light on the possible roles of glycosylation on industrially important enzymes, but also lead to the identification of cellulase glyco-variants with enhanced efficiency relative to those currently used in industrial processes.