CAREER: Glycoside Hydrolase Processivity and Substrate Recognition Mechanisms

职业：糖苷水解酶持续合成能力和底物识别机制

• 批准号: 1552355
• 负责人: Thomas Dziubla
• 金额: $ 52.45万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1552355&HistoricalAwards=false
• 关键词: CAREER; Glycoside; Hydrolase; Processivity; Substrate

Abstract: Payne (1552355)The proposed research will provide fundamental understanding of the kinetics and thermodynamics by which a class of enzymes, known as glycoside hydrolases (GHs), catalyze the breakdown of biomass into sugars that can be processed further to fuels and chemicals. The knowledge thus obtained will guide the bioengineering of these enzymes to improve their efficiency and reduce the cost of renewable bio-based approaches to a sustainable energy future. GHs break down crystalline biomass material such as cellulose or chitin by processivity - the repeated catalysis - or chewing away - of the bonds that hold the biomass material together. A number of factors related to the detailed structure and composition of both the GH and the biomass material affect the processivity. Although the processive mechanism has been the focus of numerous structural and biochemical studies, a clear connection between enzyme structure and processive function is still lacking. To this end, the proposed research focuses on developing a molecular-level understanding of the mechanisms governing GH processivity through molecular modeling and thermodynamic calculations backed by experimental biochemical characterization - the latter carried out with an international team of researchers. Although the work will primarily be directed at a model GH system utilizing chitinases, the goal will be to develop a generalized theory of GH processivity that will be assessed in the more common (and more complicated) cellulosic materials that will eventually form the basis of a renewable biomass fuel industry. The proposal also involves related elements of education and outreach - notably international research experiences for graduate students, dissemination of high performance computing tools to underserved research communities, and outreach to young girls aimed at exciting them about opportunities in science and engineering, especially in the biochemical area.

摘要：Payne（1552355）提出的研究将提供动力学和热力学的基本理解，一类酶，被称为糖苷水解酶（GHs），催化生物质分解成糖，糖可以进一步加工成燃料和化学品。由此获得的知识将指导这些酶的生物工程，以提高其效率并降低可再生生物基方法的成本，从而实现可持续能源的未来。温室气体通过不断的催化作用或咀嚼作用来分解诸如纤维素或几丁质之类的晶体生物质材料，这种作用是将生物质材料结合在一起的键。与生长激素和生物质材料的详细结构和组成有关的许多因素都会影响加工能力。虽然过程机制已成为众多结构和生化研究的焦点，但酶的结构与过程功能之间仍缺乏明确的联系。为此，建议的研究重点是通过分子建模和实验生化表征支持的热力学计算来发展对生长激素处理机制的分子水平理解-后者由一个国际研究小组进行。虽然这项工作将主要针对利用几丁质酶的生长激素模型系统，但目标将是发展一种生长激素加工能力的广义理论，该理论将在更常见（和更复杂）的纤维素材料中进行评估，这些材料最终将形成可再生生物质燃料工业的基础。该提案还涉及教育和推广的相关要素——特别是为研究生提供国际研究经验，向服务不足的研究社区传播高性能计算工具，以及向年轻女孩推广旨在激发她们在科学和工程领域，特别是生物化学领域的机会。