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-普芬特纳从可持续来源设计和生产化学品和燃料的社会能力取决于未来生物加工方面的改进。离子液体等非水溶剂可能会使生物过程的效率和经济性发生革命性的变化，特别是在用于发酵的生物质的酶前处理方面。非水溶剂赋予生物催化剂以改进的或以前未知的性质的潜力是令人兴奋的，并可能改变其在工业上的使用。尽管有这个巨大的希望，但对溶剂、酶结构和反应活性之间的关系的不完全理解阻碍了这一领域的重大科学技术发展。具体地说，缺乏的是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。在溶剂降低酶活性的情况下，与其自然环境相比，我们没有工具来系统地了解活性丧失的根本原因，也没有工具来有效地利用突变技术来克服活性损失。这个由华盛顿大学的Jim Pfaendtner提出的职业项目将开发和验证一个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(ILS)的组合。这些酶被广泛应用于生物加工应用，选择ILS是因为它们的成本效益和用作生物质增溶剂的潜力。利用先进的模拟技术，PI和他的团队将系统地确定ILS改变生长激素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的变化是基于结构、动态还是两者的组合。这个项目产生了几个更广泛的技术影响。这项研究的成功完成将带来新的生物质利用技术，这些技术可以省去一个或多个预处理阶段。此外，这项工作将创建一种通用的计算方法来研究非水环境中的酶。新方法提供了一个新水平的预测能力，将加快科学发现，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。与拟议的研究相结合的是一项广泛的外联、教育和培训计划。教学部分包括西雅图一所高中AP化学课程的模拟模块和高级本科实验室课程的新生物催化模块。研究培训的组成部分包括为当地高中教师提供研究机会，以及与校园外联组织路易斯·斯托克斯少数群体参与联盟(LSAMP)合作，让代表不足的少数群体参与PIS研究小组。该职业奖由化学、生物工程、环境和运输系统部门的催化和生物催化计划以及化学部门的化学催化计划联合颁发和赞助。