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社会设计和生产来自可持续来源的化学物质和燃料的能力依赖于生物处理的未来改进。 诸如离子液体之类的非水溶剂可能会彻底改变生物处理效率和经济性，尤其是在生物量发酵的酶促预处理中。 非水溶剂将生物催化剂赋予改善或以前未知的特性的潜力令人兴奋，并且可以改变其在行业中的使用。 尽管有这一巨大的希望，但对溶剂，酶结构和反应性之间关系的不完全理解阻碍了该领域的大量科学技术发展。 具体而言，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相关联的能力。 如果溶剂降低酶的活性，与自然环境相比，我们没有工具可以系统地了解活动丧失的根本原因，或者如何有效地使用诱变技术来克服活动损失。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项式模型工具和确定性的模型工具材料的求解，以实现新的模型和求解。 研究建议的目标是研究两种糖苷水解酶（GH）酶，并结合了三种离子液体（ILS）。 这些酶广泛用于生物处理应用中，并选择IL的成本效益和用作生物质溶解剂的潜力。 使用高级模拟技术，PI和他的组将系统地确定ILS改变GH酶活性的基本分子尺度机制。 正在追求四个研究目标，这些目标将歧视活动的变化是基于结构，动力学还是两者的组合。该项目产生了几种技术的更广泛的影响。 成功完成研究将导致新的生物量利用技术可以消除一个或多个预处理阶段。 此外，这项工作将创建一种通用计算方法，用于在非水环境中研究酶。 新方法提供了一种新的预测能力水平，可以加快科学发现，降低实验成本，并改变我们使用计算机指导生物处理设计和优化的方式。 与拟议的研究集成在一起的是广泛的外展，教育和培训计划。 教育组成部分包括西雅图高中AP化学课程的模拟模块，以及针对高级本科实验室课程的新生物催化模块。 研究培训组成部分包括为当地高中教师的研究机会以及与校园外展组织的合作，路易斯·斯托克斯（Louis Stokes）参加少数群体参与的联盟（LSAMP），以涉及PIS研究小组中代表性不足的少数民族。 该职业奖是由化学，生物工程，环境和运输系统部的催化和生物催化计划共同颁发和赞助的，化学部的化学催化计划。