co-production of 1,3 propanediol and 3HP from glycerol by clostridium pasteurianum

巴氏梭菌从甘油联产1,3丙二醇和3HP

基本信息

批准号：
1645289
负责人：
金额：
--
依托单位：
University of Nottingham
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1645289
关键词：
co production propanediol 3HP glycerol

项目摘要

To compete with existing petrochemical-based chemical manufacturing processes, low cost feedstocks for biological fermentation processes are essential, since the feedstock typically equates to over 60% of the overall production cost. Glycerol is a versatile carbon and energy source and presently it is produced in large scale as the principle by-product (10% w/w) of the biodiesel industry and it is now essentially a waste product. Clostridial species, and in particular Clostridium pasteurianum, can grow particularly well on glycerol as a sole carbon and energy source and transform it into a number of useful chemicals such as 1,3-propanediol (PDO), acetone, butanol, ethanol etc. Until now, the opportunity to use Clostridium strains for the high level production of chemicals from glycerol has been limited due to the lack of genetic engineering tools. However, the requisite tool box needed for the optimisation of the metabolic pathways required for butanol production by Clostridium pasteurianum has been developed within the Clostridia Research Group of SBRC Nottingham. It is the purpose of this PhD project to use synthetic biology approaches and the University of Nottingham tool box to generate an engineered strain of C. pasteurianum able to over-produce a number of useful chemicals using glycerol as a feedstock. The initial focus will be the important platform chemical 3-hydroxypropanoic acid (3-HP) which can serve as a starting point for production of acrylic acid (representing a $ 10 billion market together with the respective esters), acrylamide, malonic acid, poly(hydroxypropionate), 1,3-propanediol, and propiolactone. The approach taken will be to both introduce genes encoding the requisite enzymes and to knock-out genes specifying competing pathways. This will involve bringing about essential refinements to the tools available, including the generation of restriction minus hosts and the use of CRISPR/Cas9 technology. Thereafter, other products may be targeted.

要与现有的基于石化的化学制造工艺竞争，生物发酵过程的低成本原料是必不可少的，因为原料通常相当于总体生产成本的60％以上。甘油是一种多功能的碳和能源，目前它是生物柴油行业的副产品（10％w/w）的大规模生产的，现在它本质上是一种废物。梭状芽胞杆菌物种，尤其是梭菌的梭菌，可以在甘油中特别好，作为唯一的碳和能源，并将其转变为多种有用的化学物质，例如1,3-丙糖二酚（PDO），丙酮，丁醇，乙醇等。直到现在，直到现在，直到现在，才有机会使用盖植物的工具，从而有限公司使用盖晶型生产，从而有限地使用了glycerols的工具。但是，在SBRC Nottingham的Clostridia Research Group中，已经开发出了丁醇生产所需的代谢途径所需的必要工具盒。该博士学位项目的目的是使用合成生物学方法和诺丁汉大学工具盒来产生一种工程化的巴斯德念珠菌菌株，能够使用甘油作为原料过量生产多种有用的化学物质。最初的重点将是重要的平台化学化学3-羟基丙酸（3-HP），它可以作为生产丙烯酸的起点（与各自的酯一起代表了100亿美元的市场），丙烯酸，丙二酰酸，丙二酸酯，聚（羟基丙酸），1,3-丙型丙二醇和丙酸酮。所采用的方法是引入编码必要酶的基因和指定竞争途径的基因敲除基因。这将涉及对可用工具的重要改进，包括生成限制减去主机和CRISPR/CAS9技术的使用。此后，其他产品可能是针对的。