Developing second-generation hyper-producers of butanol from biomass by activating dormant pathways

通过激活休眠途径开发第二代生物质丁醇超级生产商

基本信息

批准号：
1803022
负责人：
Thaddeus Ezeji
金额：
$ 31.89万
依托单位：
Ohio State University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1803022&HistoricalAwards=false
关键词：
Developing second generation hyper producers

项目摘要

Renewable production of fuels and chemicals is growing. One strategy involves producing fuels and chemicals using microbes. Unfortunately, these chemicals often exert toxic effects on microorganisms at high concentrations. Butanol is one example of this. It has excellent properties as a transportation fuel. At high concentrations, it poisons the microbes that produce it. The central goal of the project is to enhance the ability of butanol-producing bacteria to withstand high concentrations of butanol. Undergraduate and graduate students will receive hands-on research training and mentorship. International outreach will focus on delivering a course on biofuels production in Nigeria. These experiences should prepare the students for successful careers in a global workforce.A major challenge for bioconversion of lignocellulosic biomass hydrolysates (LBH) stems from the toxicity posed by microbial inhibitory compounds (MICs) generated during metabolic processing of LBH. The long-term objective is to develop a rational approach for engineering inhibitory compound tolerance in Clostridium beijerinckii. A two-pronged strategy will be pursued. Interdependent utilization of two different waste products, glycerol and LBH, for improved solvent generation in the presence of MICs will be characterized. Also, DNA repair competence of C. beijerinckii will be increased. We hypothesize that cellular reductants [NAD(P)H] needed for detoxification of MICs and for butanol synthesis can be generated by activating a dormant pentose phosphate pathway coupled with glycerol utilization. This proposal seeks to repurpose existing pathways in C. beijerinckii to overcome metabolic hurdles. By combining metabolic engineering and reverse genetics, the project aims to uncover new determinants for butanol production by C. beijerinckii, and generate a broader framework for better microbial conversion of renewable feedstock to fuels and chemicals.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

燃料和化学品的可再生产生正在增长。一种策略涉及使用微生物生产燃料和化学物质。不幸的是，这些化学物质通常会对高浓度的微生物产生毒性作用。丁醇就是一个例子。它具有出色的特性作为运输燃料。在高浓度下，它可以毒化产生它的微生物。该项目的核心目标是增强丁醇产生的细菌承受高浓度丁醇的能力。本科生和研究生将获得动手研究培训和指导。国际外展将着重于在尼日利亚提供有关生物燃料生产的课程。这些经验应为学生在全球劳动力中的成功职业做好准备。对木质纤维素生物量水解物生物转化（LBH）的重大挑战源于在LBH代谢过程中产生的微生物抑制性化合物（MIC）所带来的毒性。长期目标是为贝吉林西克梭菌的工程抑制复合耐受性开发一种合理的方法。将采取两种策略。在麦克风存在的情况下，将两种不同的废物甘油和LBH的相互依存利用用于改进溶剂的产生。同样，北京梭菌的DNA维修能力将提高。我们假设可以通过激活休眠的磷酸五磷酸五磷酸途径以及甘油利用率来产生麦克风和丁醇合成所需的细胞还原剂[NAD（P）H]。该提议旨在重新利用C. beijerinckii中的现有途径，以克服代谢障碍。通过结合代谢工程和反向遗传学，该项目旨在揭示北京C. beijerinckii生产的新决定因素，并生成更广泛的框架，以更好地将可再生原料转换为燃料和化学物质的微生物转化。这项奖项反映了NSF的法定任务，反映了通过评估的构成者的构成师的构成师的影响力，这一奖项被认为是构成的依据。