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.

主要由化石燃料燃烧引起的人为二氧化碳排放导致大气中二氧化碳浓度增加。由于气候变化带来的日益严重的环境问题和不确定性以及这些燃料不可避免的限制，需要开发替代的、可持续的燃料和化学品生产路线。生物替代品的发展主要集中在糖基发酵上。然而，这些方法受到可食用原料成本的影响。一种较便宜的替代原料是粗甘油，它是生物柴油生产的主要副产品。生物柴油经济的增长导致该原料的价格大幅下降。这种副产品的处理对于生物柴油公司来说是一个沉重的负担。甘油的利用将提高从原料中回​​收有价值的产品，并通过降低产品价格有利于生物柴油的生产。 甘油利用的一种有希望的候选者是严格厌氧细菌巴氏梭菌。梭菌属细菌在使用底物的灵活性和对有毒化合物的耐受性方面比经典模型生物如酿酒酵母或大肠杆菌具有巨大优势。然而，用于研究和改造这些生物体的复杂遗传工具才刚刚开始出现。巴氏梭菌自然产生甘油 1,3-丙二醇 (1,3-PD) 的最终产品，这是一种具有工业价值的化学中间体，可用于合成聚酯等聚合物。当用甘油生产 1,3-PD 以提供必要的还原当量时，代谢限制会导致不可避免的副产物形成。将这些天然的低价值副产品改为更理想的副产品，如 3-氢丙酸 (3-HP)，可以大大降低产品的价格。 3-HP 是一种很有前途的 C3 结构单元，用于合成商品和特种化学品，并且可以还原为 1,3-PD。 拟议项目旨在对巴氏梭菌进行代谢工程，以从甘油中联产 1,3-PD 和 3-HP。因此，将引入产生3-HP的异源途径，并培育产生1,3-PD的天然途径。此外，基因改造将防止不需要的副产物的形成。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结构单元，并有望有助于改善和支持生物柴油的生产。该项目不仅将为生产有价值的化学品带来理想的生物转化，而且有望为工业和医学上重要的梭状芽胞杆菌属细菌迄今为止尚未开发的遗传工具带来改进和进步。它还将提高对新陈代谢的理解。