Production of succinic acid with engineered genetic switches in methylobacterium extorquens

利用扭扭甲基杆菌中的工程基因开关生产琥珀酸

基本信息

  • 批准号:
    463079-2014
  • 负责人:
  • 金额:
    $ 3.54万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Collaborative Research and Development Grants
  • 财政年份:
    2014
  • 资助国家:
    加拿大
  • 起止时间:
    2014-01-01 至 2015-12-31
  • 项目状态:
    已结题

项目摘要

Succinic acid is one of the 12 most important molecules in the modern chemical industry. It is used in many applications, including the production of polymers such as PBS (polybutylsuccinate). Currently, almost all of the succinic acid production originates from fossil-carbon. In order to find other sources and rely less on petroleum, so that the succinic industry can embrace a "green approach", many companies have started projects to produce succinic acid by fermentation from biological raw material, mainly sugars derived from crops. However, this greener product is controversial because it diverts agricultural land and ressources that could potentially be used for crops intended for food towards the chemical industry instead. For the past few years, this debate has been gaining in importance and thus industry is starting to envision second generation processes that would rely on cellulose or waste. In this project, the source of raw material used for fermentation does not compete with human or animal food, but rather uses bio-methanol derived from waste by gazeification (thermo-chimio-conversion). In an initial phase of the project, the feasibility of using Methylobacterium extorquens to produce succinic acid for industrial processes has been evaluated. The methylotrophic bacteria M. extorquens is capable of consuming methanol and has the citric acid cycle; it is thus capable of producing succinic acid. Therefore, a knockout of the sdh gene, which converts succinate to fumarate, has already been performed. However, because this gene is essential, the knockout strains survive only with the addition of malate to rescue the citric acid cycle. To circumvent this problem and achieve succinic acid production in a range close to 10-20g/L, we have three main objectives. 1) Engineer a sdh knockout strain complemented with an inducible sdh. This requires the design and implementation of new genetic switches with promoters compatible with M. extorquens. 2) Similarly, engineer inducible small RNAs that repress sdh to tune expression according to succinic acid production needs. 3) Convert the biomass accumulated in the form of poly-ß-hydroxybutyrate (PHB) to succinic acid by genetically rewiring the PHB degradation pathways.
琥珀酸是现代化学工业中最重要的12种分子之一。它用于许多应用,包括生产聚合物,如PBS(聚丁二酸丁酯)。目前,几乎所有的琥珀酸生产都来自化石碳。为了寻找其他来源,减少对石油的依赖,使琥珀酸工业能够采用“绿色方法”,许多公司已经开始通过生物原料,主要是来自农作物的糖发酵生产琥珀酸的项目。然而,这种更绿色的产品是有争议的,因为它将可能用于粮食作物的农业土地和资源转移到化学工业。在过去的几年里,这一争论越来越重要,因此工业界开始设想依赖纤维素或废物的第二代工艺。在该项目中,用于发酵的原材料来源不会与人类或动物食品竞争,而是使用通过气化(热化学转化)从废物中提取的生物甲醇。在该项目的初始阶段,已经评估了使用扭脱甲基杆菌生产琥珀酸用于工业过程的可行性。甲基营养菌M.脱醌能够消耗甲醇并具有柠檬酸循环;因此它能够产生琥珀酸。因此,将琥珀酸转化为富马酸的sdh基因的敲除已经完成。然而,由于该基因是必需的,敲除菌株只能在添加苹果酸以拯救柠檬酸循环的情况下存活。为了避免这个问题并实现接近10- 20 g/L范围内的琥珀酸生产,我们有三个主要目标。1)工程改造sdh敲除菌株,并补充诱导型sdh。这就需要设计和实施新的基因开关,其启动子与M.扭体2)类似地,根据琥珀酸生产的需要,设计抑制sdh的可诱导小RNA来调节表达。3)通过基因重组聚β-羟基丁酸酯(PHB)降解途径,将以聚β-羟基丁酸酯(PHB)形式积累的生物质转化为琥珀酸。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Perreault, Jonathan其他文献

Ro-associated Y RNAs in metazoans: Evolution and diversification
  • DOI:
    10.1093/molbev/msm084
  • 发表时间:
    2007-08-01
  • 期刊:
  • 影响因子:
    10.7
  • 作者:
    Perreault, Jonathan;Perreault, Jean-Pierre;Boire, Gilles
  • 通讯作者:
    Boire, Gilles
Simple rolling circle amplification colorimetric assay based on pH for target DNA detection
  • DOI:
    10.1016/j.talanta.2019.04.003
  • 发表时间:
    2019-08-15
  • 期刊:
  • 影响因子:
    6.1
  • 作者:
    Hamidi, Seyed Vahid;Perreault, Jonathan
  • 通讯作者:
    Perreault, Jonathan
Identification of quorum sensing-controlled genes in Burkholderia ambifaria.
  • DOI:
    10.1002/mbo3.67
  • 发表时间:
    2013-04
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Chapalain, Annelise;Vial, Ludovic;Laprade, Natacha;Dekimpe, Valerie;Perreault, Jonathan;Deziel, Eric
  • 通讯作者:
    Deziel, Eric
Novel Strategies to Optimize the Amplification of Single-Stranded DNA

Perreault, Jonathan的其他文献

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{{ truncateString('Perreault, Jonathan', 18)}}的其他基金

Discovery and characterization of noncoding RNAs in prokaryotes
原核生物中非编码 RNA 的发现和表征
  • 批准号:
    RGPIN-2019-06403
  • 财政年份:
    2022
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Discovery Grants Program - Individual
Discovery and characterization of noncoding RNAs in prokaryotes
原核生物中非编码 RNA 的发现和表征
  • 批准号:
    RGPIN-2019-06403
  • 财政年份:
    2021
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Discovery Grants Program - Individual
Electrochemical drug sensing with hydrophobic compound-adapted aptamers
使用疏水性化合物适配适配体进行电化学药物传感
  • 批准号:
    521437-2018
  • 财政年份:
    2020
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Strategic Projects - Group
Sensitive and specific electrochemical detection of COVID-19 (SARS-CoV2) based on isothermal amplification
基于等温扩增的 COVID-19 (SARS-CoV2) 的灵敏且特异的电化学检测
  • 批准号:
    554464-2020
  • 财政年份:
    2020
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Alliance Grants
Discovery and characterization of noncoding RNAs in prokaryotes
原核生物中非编码 RNA 的发现和表征
  • 批准号:
    RGPIN-2019-06403
  • 财政年份:
    2020
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Discovery Grants Program - Individual
Electrochemical drug sensing with hydrophobic compound-adapted aptamers
使用疏水性化合物适配适配体进行电化学药物传感
  • 批准号:
    521437-2018
  • 财政年份:
    2019
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Strategic Projects - Group
Discovery and characterization of noncoding RNAs in prokaryotes
原核生物中非编码 RNA 的发现和表征
  • 批准号:
    RGPIN-2019-06403
  • 财政年份:
    2019
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Discovery Grants Program - Individual
Aptamers and riboswitches as models to help tune NMR-based screening methods to find small molecules that target RNA
适体和核糖开关作为模型,帮助调整基于 NMR 的筛选方法,以找到靶向 RNA 的小分子
  • 批准号:
    533439-2018
  • 财政年份:
    2018
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Engage Grants Program
Electrochemical drug sensing with hydrophobic compound-adapted aptamers**
使用疏水性化合物适配适配体进行电化学药物传感**
  • 批准号:
    521437-2018
  • 财政年份:
    2018
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Strategic Projects - Group
Non-coding RNA function and cations: studying the biological roles of the hammerhead ribozyme
非编码RNA功能和阳离子:研究锤头核酶的生物学作用
  • 批准号:
    418240-2012
  • 财政年份:
    2018
  • 资助金额:
    $ 3.54万
  • 项目类别:
    Discovery Grants Program - Individual

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Sustainable Succinic Acid Production using an Integrated Electrochemical Bioreactor and Renewable Feedstock
使用集成电化学生物反应器和可再生原料进行可持续琥珀酸生产
  • 批准号:
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开发用于琥珀半醛脱氢酶缺乏症 (SSADHD) 基因替代疗法的诱导小鼠模型
  • 批准号:
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开发用于琥珀半醛脱氢酶缺乏症 (SSADHD) 基因替代疗法的诱导小鼠模型
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