Collaborative Research: Metabolically Engineered Organisms for Conversion of Cellulose to Isobutanol

满足世界快速增长的能源需求，同时保护地球日益受到威胁的气候和生态平衡，是社会面临的最大挑战之一。本项目将通过构建一个将纤维素转化为异丁醇的嗜热微生物平台，探索一条从生物质中生产先进液体燃料的新途径。异丁醇与目前的发动机兼容，具有更高的能量密度，优于乙醇作为燃料。异丁醇可以替代日益减少且政治上不稳定的石油供应，而不会导致全球变暖。与乙醇不同，异丁醇可以利用现有的技术和基础设施纳入能源经济。为了解决利用纤维素作为原料的先进生物燃料研究的基本障碍，目标将是开发一种嗜热和（部分）纤维素分解的地杆菌宿主生物来生产纤维素酶，以增强天然纤维素分解活性。这种生物在适度升高的温度下生长的能力，其中纤维素酶高度活跃，并利用通常抑制纤维素酶的纤维素降解的糖产物，将提高性能，并最大限度地减少在发酵过程中额外添加昂贵的酶以产生生物燃料的需要。该项目的具体目标将是产生稳定的、活性的细菌纤维素酶，并在地杆菌中表达这些新酶。同时，异丁醇途径将在这个中度嗜热宿主中建立。最终目标将是整合和优化纤维素降解和异丁醇生产途径。更广泛的影响：这项研究工作将在蛋白质和代谢工程方面培养一些世界上最有才华的学生和博士后研究人员，这两项技术在生物技术行业，特别是快速增长的生物燃料/化学工业中有着非常强烈的需求。该项目将支持广泛的本科生研究，同时与众多外展项目对接。教育计划包括联合研究会议和研究生的联合指导，以及将部分研究项目整合到实验课程的模块中。该项目提出了一种新的方法来解决社会面临的最大挑战之一，即开发可再生的运输燃料和化学品。

Meeting the world's rapidly growing energy needs while protecting Earth's increasingly threatened climate and ecological balance is one of the greatest challenges facing society. This project will explore a new route to producing an advanced liquid fuel from biomass by constructing a thermophilic microbial platform to convert cellulose to isobutanol. Compatible with current engines and with higher energy density, isobutanol is superior to ethanol as a fuel. Isobutanol can replace dwindling and politically unstable petroleum supplies without contributing to global warming and, unlike ethanol, can be incorporated into the energy economy using current technology and infrastructure. To target the fundamental hurdle in advanced biofuel research of utilizing cellulose as the feedstock, the goal will be to develop a thermophilic and (partially) cellulolytic Geobacillus host organism to produce cellulase(s) to augment the native cellulolytic activity. The ability of this organism to grow at the moderately elevated temperatures where cellulases are highly active and to utilize the sugar products of cellulose degradation that normally inhibit the cellulases will enhance performance and minimize the need for additional expensive enzyme addition during fermentation to generate biofuels. Specific objectives of this project will be to generate stable, active bacterial cellulases and express those new enzymes in Geobacillus. Simultaneously, the isobutanol pathway will be established in this moderately thermophilic host. The final goal will be to integrate and optimize cellulose degradation and isobutanol production pathways. Broader impacts: This research effort will train some of the most talented students and postdoctoral researchers in the world in protein and metabolic engineering, two technologies that are in very strong demand in the biotechnology industry, particularly the rapidly-growing biofuels/chemicals industry. This project will support extensive undergraduate research while interfacing with numerous outreach programs. The educational plan includes joint research meetings and co-advising of graduate students as well as the integration of parts of the research project into modules for laboratory courses. This project proposes a novel approach to addressing one of society's greatest challenges, developing a renewable source of transportation fuels and chemicals.