CAREER: Integrating Chemical and Biological Catalysis for the Sustainable Production of Biofuels and Commodity Chemicals

这项由生物技术、生化和生物质工程项目授予的美国国家科学基金会职业奖支持一种将木质纤维素生物质转化为燃料和化学品的新方法，该方法可以绕过葡萄糖中心过程中使用的酶糖化。PI假设，通过将木质纤维素材料转化为乙酰丙酸而不是葡萄糖，然后结合合成生物学和代谢工程来开发微生物，从而有效地将乙酰丙酸转化为所需的碳氢化合物燃料或化学品，可以开发出潜在的更经济的生物燃料和生物可再生化学工艺。由于乙酰丙酸可以通过木质纤维素生物质的酸水解以高产量生产，因此这种生产生物燃料和生物可再生化学品的途径避免了在传统工艺中将生物质转化为可发酵糖所需的昂贵的酶降解步骤。研究小组将利用合成生物学对细菌进行代谢工程，使其分解乙酰丙酸作为生长和合成碳氢化合物燃料的唯一碳源。提出的工作将阐明以前未知的生化途径，研究工程分解代谢的方法，并评估替代生物质到化学物质的过程。该建议建立在过去工程大肠杆菌过量生产脂肪酸产品的工作基础上，并整合了已建立的代谢建模、生物化学、系统生物学和基因工程方法。可持续化学生产过程的发展将需要培训具有应用代谢工程和合成生物学能力的新一代化学工程师。为了应对这一挑战，PI将重新设计生化工程的实验课程，并将继续发展iGEM项目（国际基因工程机器），作为威斯康星大学麦迪逊分校跨学科研究和教育的典范。通过iGEM，本科生团队在合成生物学领域设计、实施和交流实验研究项目，并将与nsf赞助的Delta项目合作，开发教育材料，向年轻学生介绍可持续性、生物能源、工程和合成生物学的概念。

CBET 1149678 - PflegerThis NSF CAREER award by the Biotechnology, Biochemical and Biomass Engineering program supports a novel approach to converting lignocellulosic biomass to fuels and chemicals that bypasses enzymatic saccharification used in glucose centric processes. The PI hypothesizes that potentially more economical biofuel and biorenewable chemical processes can be developed by converting lignocellulosic materials to levulinic acid instead of glucose, and then using a combination of synthetic biology and metabolic engineering to develop microoganisms to efficiently convert levulinic acid into the desired hydrocarbon fuel or chemical. Since levulinic acid can be produced in high yields via the acid hyrolysis of lignocellulose biomass, this route to biofuels and biorenewable chemicals avoids the costly enzymatic degradation steps needed in traditional processes to convert biomass into fermentable sugars.The research team will use synthetic biology to metabolically engineer a bacterium to catabolize levulinic acid as the sole carbon source for growth and the synthesis of drop-in hydrocarbon fuels. The proposed work will elucidate a previously unknown biochemical pathway, examine methods of engineering catabolism, and evaluate an alternative biomass-to-chemicals process. The proposal builds upon past work to engineer Escherichia coli to overproduce fatty-acid based products and integrates established metabolic modeling, biochemistry, systems biology, and genetic engineering approaches.The development of sustainable chemical production processes will require the training of a new generation of chemical engineers possessing the ability to apply metabolic engineering and synthetic biology. To meet this challenge, the PI will redesign a laboratory course in biochemical engineering, will continue the development of the iGEM program (international Genetically Engineered Machines) as a model for interdisciplinary research and education at UWMadison. Through iGEM, undergraduate teams design, conduct, and communicate experimental research projects in the field of synthetic biology, and will partner with the NSF-sponsored Delta program to develop educational materials for introducing younger students to the concepts of sustainability, bioenergy, engineering, and synthetic biology.