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

有了这个奖项，化学部的生命过程化学项目资助科罗拉多大学博尔德分校的Zhongping Tan博士研究纤维素酶的糖基化，纤维素酶是一类重要的酶，广泛应用于工业中生产可再生生物材料（生物燃料）衍生的燃料。 为了降低生产生物燃料的成本，最重要的是增强纤维素酶和糖基化的性能，即，碳水化合物与蛋白质的连接似乎是实现这一任务的有希望的方法。该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。通过这个项目的工作，学生将获得跨化学和生物学的各种技能和经验。该项目包括对中小学理科教师进行可再生生物燃料生产教育的计划。 通过化学合成，酶促生物转化和生化表征的结合使用，本研究项目旨在揭示纤维素酶糖基化的分子水平的影响。所提出的方法将使用化学和酶促合成来制备均质糖基化蛋白同种型（糖型）的文库，其中控制所占据的糖基化位点的数目和聚糖组成。糖基化对稳定性和功能的影响将通过比较这些明确定义的糖型阵列的特征来定量。预计这种类型的系统知识不仅阐明了糖基化对工业上重要的酶的可能作用，而且还导致相对于目前在工业过程中使用的那些具有增强的效率的纤维素酶糖变体的鉴定。

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.