CAREER: Computational Enzymology of Non-Aqueous Biocatalysis: Application to Biomass Pretreatment

职业：非水生物催化的计算酶学：在生物质预处理中的应用

• 批准号: 1150596
• 负责人: Jim Pfaendtner
• 金额: $ 45万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1150596&HistoricalAwards=false
• 关键词: CAREER; Computational; Enzymology; Non; Aqueous

1150596-Pfaendtner Societal ability to design and produce chemicals and fuels from sustainable sources relies on future improvements in bioprocessing. Non-aqueous solvents such as ionic liquids may potentially revolutionize bioprocess efficiency and economics, particularly in the enzymatic pretreatment of biomass for fermentation. The potential for non-aqueous solvents to endow biological catalysts with improved or previously unknown properties is exciting and could transform their use in industry. In spite of this great promise, the incomplete understanding of the relationship between solvent, enzyme structure, and reactivity has hampered significant scientific technological development in this arena. Specifically, what is lacking is the ability to relate molecular features of the solvent to its effect on enzyme stability and activity. In cases where solvents lower the activity of the enzyme compared with its natural environment we do not have the tools to systematically understand the root cause of the loss of activity or how to effectively use mutagenesis techniques to overcome the activity loss.This CAREER project put forward By Jim Pfaendtner of the University of Washington will develop and validate a new multi-scale computational modeling toolkit for the discovery and optimization of bioprocess solvent environments. The target of the research proposal is the investigation of two glycoside hydrolase (GH) enzymes with a combination of three ionic liquids (ILs). These enzymes are widely used in bioprocessing applications and the ILs are chosen for their cost effectiveness and potential for use as biomass solubilization agents. Using advanced simulation techniques the PI and his group will systematically determine the underlying molecular scale mechanisms by which ILs change the activity of GH enzymes. Four research objectives are being pursued that will discriminate whether the activity changes are based on structure, dynamics or a combination of both. There are several technological broader impacts stemming from this project. Successful completion of the research will lead to new biomass utilization technologies that could eliminate one or more pretreatment stages. Additionally, this work will create a general computational approach for studying enzymes in non-aqueous environments. The new approach offers a new level of predictive capability that will speed scientific discovery, reduce experimental costs, and transform the way we use computers to guide bioprocess design and optimization. Integrated with the proposed research is an extensive outreach, education and training plan. Educational components include a simulation module for an AP chemistry class at a Seattle High School and a new biocatalysis module for the senior undergraduate laboratory course. Research training components include research opportunities for local High School teachers and collaboration with a campus outreach organization, Louis Stokes Alliance for Minority Participation, (LSAMP) to involve under-represented minorities in the PIs research group. This CAREER award is jointly made and sponsored by the Catalysis and Biocatalysis Program of the Chemical, Bioengineering, Environmental, and Transport Systems Division and the Chemical Catalysis Program of the Division of Chemistry.

1150596-Pfaendtner 从可持续来源设计和生产化学品和燃料的社会能力依赖于生物加工的未来改进。 非水溶剂如离子液体可能会彻底改变生物过程的效率和经济性，特别是在生物质发酵的酶促预处理中。 非水溶剂赋予生物催化剂改进或以前未知的性能的潜力是令人兴奋的，并且可能会改变它们在工业中的用途。 尽管前景广阔，但对溶剂、酶结构和反应性之间关系的不完全理解阻碍了这一领域的重大科学技术发展。 具体来说，缺乏将溶剂的分子特征与其对酶稳定性和活性的影响联系起来的能力。 如果与自然环境相比，溶剂降低了酶的活性，我们没有工具来系统地了解活性丧失的根本原因，或者如何有效地使用诱变技术来克服活性丧失。华盛顿大学的 Jim Pfaendtner 提出的这个职业项目将开发和验证一种新的多尺度计算建模工具包，用于发现和优化生物过程溶剂环境。 该研究计划的目标是研究两种糖苷水解酶（GH）与三种离子液体（IL）的组合。 这些酶广泛用于生物加工应用，选择离子液体是因为其成本效益和用作生物质增溶剂的潜力。 使用先进的模拟技术，PI 和他的团队将系统地确定 IL 改变 GH 酶活性的潜在分子尺度机制。 正在追求的四个研究目标将区分活动变化是基于结构、动态还是两者的组合。该项目产生了一些更广泛的技术影响。 该研究的成功完成将带来新的生物质利用技术，可以消除一个或多个预处理阶段。 此外，这项工作还将创建一种用于研究非水环境中酶的通用计算方法。 新方法提供了新水平的预测能力，将加速科学发现，降低实验成本，并改变我们使用计算机指导生物过程设计和优化的方式。 与拟议研究相结合的是广泛的外展、教育和培训计划。 教育部分包括西雅图高中 AP 化学课程的模拟模块和高年级本科生实验室课程的新生物催化模块。 研究培训内容包括为当地高中教师提供研究机会，以及与校园外展组织路易斯·斯托克斯少数族裔参与联盟 (LSAMP) 合作，让代表性不足的少数族裔参与 PI 研究小组。 该职业奖由化学、生物工程、环境和运输系统学部催化与生物催化项目和化学学部化学催化项目联合设立并赞助。