SBIR Phase IB: Metabolic Engineering for Clostridial Biotechnology

该小型企业创新研究（SBIR）IB期项目旨在开发适用于可再生原料工业规模酒精生产的平台梭菌菌株，并改善所有梭菌的代谢工程技术。梭菌是严格厌氧的内生孢子形成原核生物，对纤维素降解、人类和动物的健康和生理以及简单和复杂碳水化合物的厌氧降解非常重要。这些生物体的工业用途的障碍包括遗传和代谢工程工具和策略的开发，这些工具和策略可能导致菌株适合于从可再生原料生产化学品和燃料。该项目的重点是开发代谢工程策略和产溶剂梭菌菌株，用于生产化学品和生物燃料。通过新的方法，该项目旨在解决三个重要的生物加工瓶颈：1）产品形成特性，2）产品收率和选择性，3）重复补料分批或连续发酵的合适特性。该项目的预期成果是克服上述生物加工瓶颈的梭菌菌株和适用于所有梭菌的改进的代谢工程技术。该项目的商业影响包括开发改进的生物炼制和生物燃料技术。用于生产化学品和燃料的石油供应变得越来越有限和不可靠。此外，不可再生化学品和燃料的使用或燃烧对我们星球的气候产生有害影响。生物质是一种碳中和的可再生资源，用于生产化学品和燃料，也是生物炼制概念的基础。产溶剂丁酸梭菌在过去丙酮和丁醇的生产中发挥了重要的工业作用。产溶剂梭菌的代谢工程可以导致用于生产化学品如丁酸、丁醇、丁二醇、丙醇和乙偶姻以及生产氢的工业过程。其中一些化学品可以直接用作生物燃料，而其他化学品可以用于化学转化为生物燃料。这些生物的主要优点是它们可以直接发酵大量的简单和复杂碳水化合物，包括木质纤维素，而只需最少的预处理。代谢工程的产溶剂梭菌的商业潜力是特殊的，但仍在很大程度上未开发。该项目旨在捕捉和展示这一潜力的一部分。

This Small Business Innovation Research (SBIR) Phase IB project aims to develop platform clostridia strains suitable for industrial scale alcohol production from renewable feedstocks and also to improve metabolic engineering technologies for all clostridia. Clostridia are strictly anaerobic endospore forming prokaryotes of major importance to cellulose degradation, human and animal health and physiology, and anaerobic degradation of simple and complex carbohydrates. Obstacles for the industrial use of these organisms include the development of genetic and metabolic engineering tools and strategies that could lead to strains suitable for production of chemicals and fuels from renewable feedstocks. This project focuses on developing metabolic engineering strategies and strains of solventogenic clostridia for the production of chemicals and biofuels. Through novel approaches, this project aims to solve three important bioprocessing bottlenecks: 1) product formation characteristics, 2) product yield and selectivity, 3) and suitable characteristics for repeated fed-batch or continuous fermentations. Anticipated outcomes of this project are clostridia strains that overcome the aforementioned bioprocessing bottlenecks and improved metabolic engineering technologies that are applicable to all clostridia. The borader/commercial impacts of this project include the development of improved biorefinery and biofuel technologies. Oil supplies for producing chemicals and fuels are becoming increasingly limiting and unreliable. Moreover, use or combustion of non-renewable chemicals and fuels detrimentally impacts the climate of our planet. Biomass is a carbon-neutral renewable resource for producing chemicals and fuels and the basis for the biorefinery concept. Solventogenic, butyric-acid clostridia played a major industrial role in the production of acetone and butanol in the past. Metabolic engineering of solventogenic clostridia may lead to industrial processes for production of chemicals such as butyric acid, butanol, butanediol, propanol, and acetoin, and production of hydrogen. Some of these chemicals can serve as biofuels directly, while others can be used for chemical conversion to biofuels. A major advantage of these organisms is that they can directly ferment a large spectrum of simple and complex carbohydrates including lignocellulosics with minimal pretreatment. The commercial potential of metabolically engineered solventogenic clostridia is exceptional but remains largely unexplored. This project aims to capture and demonstrate part of this potential.