Coproduction of 1,3-propanediol and 3-hydroxypropionic acid from glycerol by Clostridium pasteurianum

巴氏梭菌从甘油联产1,3-丙二醇和3-羟基丙酸

• 批准号: 290250425
• 负责人: Dr. Kai Schuchmann
• 金额: --
• 依托单位: Clostridial Research Group
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/290250425?language=en
• 关键词: Coproduction; propanediol; hydroxypropionic; acid; glycerol

Human-caused CO2 emissions predominantly caused by the combustion of fossil fuels is leading to increased atmospheric CO2 concentrations. Rising environmental concerns and uncertainties regarding the climate changes and the inevitable limitation of these fuels necessitate the development of alternative, sustainable routes to fuels and chemical production. Developments of biological alternatives have been mainly focused on sugar-based fermentations. However, these processes suffer from the cost of the edible feedstock. One alternative less expensive feedstock is raw glycerol, the primary by-product of biodiesel production. Growth of the biodiesel economy led to a significant decrease of the price of this feedstock. Disposal of this by-product is a severe burden for biodiesel companies. Utilization of glycerol would improve the recovery of valuable products from the feedstock and benefit biodiesel production by lowering the price of the product. One promising candidate for glycerol utilization is the strictly anaerobic bacterium Clostridium pasteurianum. Bacteria of the genus Clostridium have tremendous advantages over classic model organisms such as Saccharomyces cerevisiae or Escherichia coli with respect to flexibility of substrates utilized and tolerance to toxic compounds. However, sophisticated genetic tools for study and modification of these organisms have just started to become available. C. pasteurianum naturally produces as end-product from glycerol 1,3-propanediol (1,3-PD), an industrially valuable chemical intermediate that can be used, for example, for the synthesis of polymers such as polyesters. Metabolic constraints lead to inevitable by-product formation when 1,3-PD is produced from glycerol to provide necessary reducing equivalents. Changing these natural low value by-products to a more desirable such as 3-hydroypropionic acid (3-HP) can drastically lower the price of the product. 3-HP is a promising C3 building block for the synthesis of commodity as well as specialty chemicals and can be reduced to 1,3-PD. The proposed project aims at the metabolic engineering of C. pasteurianum for the coproduction of 1,3-PD and 3-HP from glycerol. Therefore, a heterologous pathway leading to 3-HP will be introduced and the native pathway to 1,3-PD will be fostered. Furthermore, genetic modifications will prevent the formation of unwanted side products. This sustainable process will employ the cheap and abundant feedstock glycerol and generate important chemical building blocks and will hopefully help to improve and support biodiesel production. The project will not only lead to a desirable biological conversion for the production of valuable chemicals but will hopefully lead to improvements and advances of the so far underdeveloped genetic tools for bacteria of the industrially and medically important genus Clostridium. It will also improve the understanding of the metabolism.

人为引起的二氧化碳排放主要由化石燃料的燃烧引起，导致大气中的二氧化碳浓度升高。对气候变化以及这些燃料不可避免的限制的环境问题和不确定性的增加，需要开发替代性，可持续的燃料和化学生产路线。生物替代品的发展主要集中在基于糖的发酵上。但是，这些过程遭受可食用原料的成本。一种替代较便宜的原料是生物柴油生产的主要副产品生甘油。生物柴油经济的增长导致该原料的价格大大降低。对于生物柴油公司来说，处置该副产品是一个重大负担。甘油的利用将改善从原料中恢复有价值的产品，并通过降低产品价格使生物柴油生产受益。 甘油利用率的一个有希望的候选者是严格的厌氧菌梭菌巴斯德里亚植物。对于经典模型生物（例如酿酒酵母）或大肠杆菌（Escherichia Coli）的细菌，就利用的底物的柔韧性和对有毒化合物的耐受性而言，具有巨大的优势。但是，用于研究和修饰这些生物的复杂遗传工具刚刚开始可用。 C. dasteurianum自然会产生甘油1,3-丙二醇（1,3-PD）的最终产物，这是一种工业上有价值的化学中间体，可用于例如合成聚合物（如多植物）。当甘油产生1,3-PD以提供必要的减少等效物时，代谢约束会导致不可避免的副产品形成。将这些自然低价值的副产品更改为更理想的，例如3-氢丙酸（3-HP）可以大大降低产品价格。 3-HP是合成商品和特种化学品的有前途的C3构建块，可以将其降低至1,3-PD。 拟议的项目旨在用于巴氏梭菌的代谢工程，用于从甘油中共同制作1,3-PD和3-HP。因此，将引入通往3-HP的异源途径，并将培养到1,3-PD的天然途径。此外，遗传修饰将防止形成不良的副产品。这种可持续的过程将采用廉价且丰富的原料甘油，并产生重要的化学基础，并希望有助于改善和支持生物柴油生产。该项目不仅会导致产生有价值的化学物质的理想生物学转化，而且有望导致迄今为止迄今为止迄今欠发达的遗传工具的改进和进步，用于工业和医学上重要的梭状芽胞杆菌的细菌。它还将改善对新陈代谢的理解。