Collaborative Research: Mechanisms for Cell Membrane Damage during Production of Biorenewable Fuels

合作研究:生物可再生燃料生产过程中细胞膜损伤的机制

基本信息

  • 批准号:
    1604646
  • 负责人:
  • 金额:
    $ 19.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-01 至 2022-08-31
  • 项目状态:
    已结题

项目摘要

The conversion of plant biomass to biofuels by fermentation of biomass-derived sugars to alcohols is a sustainable route for renewable fuels production. However, during the fermentation process, the biofuel molecules produced are often toxic to the fermenting organism at high concentrations, which lowers the overall biofuel production capacity. One way to address this problem is redesign the membrane surrounding the fermenting cell, so that the organism can be more tolerant to high concentrations of biofuel dissolved in the liquid water surrounding it. This collaborative project will develop a fundamental understanding of how biofuel molecules such as ethanol interact with the cell membrane of yeast, a fermenting microorganism. The key innovation is use of sophisticated molecular dynamic simulation tools to model these interactions on computer. These studies will suggest strategies to target genetic engineering of the yeast cell to express cell membranes that improve the overall tolerance of the cell to high concentrations of biofuel, so that biofuel production is improved. The educational activities associated with this project include a middle- and high school outreach program designed to highlight how experiments and theory work together to solve important scientific problems, coordinated through programs at Iowa State University and the University of Maryland.The overall goal of this collaborative research is to gain a fundamental understanding of the cellular and biomolecular interactions of the microbial membranes with model biofuel molecules known to influence membrane disruption. The research will suggest how cell membranes can be engineered so that the cell is more tolerant to these biofuel molecules. The research plan will focus on how Saccharomyces cerevisiae membranes interact with model biofuel molecules or intermediates, including ethanol, octanoic acid, and n-butanol. These efforts will inform genetic engineering approaches to design cell membranes that improve the tolerance of the yeast cell to these biofuel molecules. Key membrane metrics include porosity, fluidity, hydrophobicity and rigidity. The research plan has three objectives. The first objective is to establish theoretical and experimental model membrane systems, using ethanol as a well-characterized model inhibitor. The theoretical approach will use molecular dynamics simulations to reveal how the molecular character and lipid composition of the membrane influence ethanol-mediated membrane disruption. The second objective is to probe the interaction of octanoic acid and n-butanol with model membrane systems developed under the first objective. More complex membrane systems will be considered to determine the effect of ergosterol, chain unsaturation, and lipid head groups on membrane disrupter toxicity. Membrane vesicles assembled in vitro will be compared vesicles made from whole cells as well as intact whole cells to establish model membrane of lipid mixtures to living systems. The third objective is to use molecular dynamics simulations to predict the improved tolerance of membranes with altered lipid head group concentrations, chain saturation, chain branching, and ergosterol concentration. Membranes with improved tolerance will be tested in vitro and then expressed and tested in engineered S. cerevisiae cells.
通过生物质衍生的糖发酵成醇而将植物生物质转化为生物燃料是可再生燃料生产的可持续途径。 然而,在发酵过程中,产生的生物燃料分子在高浓度下通常对发酵生物体有毒,这降低了整体生物燃料生产能力。 解决这一问题的方法之一是重新设计发酵细胞周围的膜,使生物体能够更耐受溶解在其周围液态水中的高浓度生物燃料。该合作项目将从根本上了解乙醇等生物燃料分子如何与发酵微生物酵母的细胞膜相互作用。 关键的创新是使用复杂的分子动力学模拟工具在计算机上模拟这些相互作用。这些研究将提出针对酵母细胞的基因工程的策略,以表达细胞膜,提高细胞对高浓度生物燃料的整体耐受性,从而提高生物燃料的生产。与该项目相关的教育活动包括一个初中和高中外展计划,旨在突出实验和理论如何共同解决重要的科学问题,通过爱荷华州州立大学和马里兰州大学的项目进行协调。这项合作研究的总体目标是从根本上了解微生物膜与模型生物燃料的细胞和生物分子相互作用已知影响膜破裂的分子。 这项研究将提出如何改造细胞膜,使细胞对这些生物燃料分子更具耐受性。 该研究计划将重点关注酿酒酵母膜如何与模型生物燃料分子或中间体相互作用,包括乙醇,辛酸和正丁醇。 这些努力将为基因工程方法提供信息,以设计细胞膜,提高酵母细胞对这些生物燃料分子的耐受性。 关键的膜指标包括孔隙率、流动性、疏水性和刚性。 研究计划有三个目标。第一个目标是建立理论和实验模型膜系统,使用乙醇作为一个良好的特征模型抑制剂。 理论方法将使用分子动力学模拟来揭示膜的分子特征和脂质组成如何影响乙醇介导的膜破裂。 第二个目标是探索辛酸和正丁醇与模型膜系统下开发的第一个目标的相互作用。将考虑更复杂的膜系统,以确定麦角固醇,链不饱和度,和脂质头基团对膜破坏剂毒性的影响。 将体外组装的膜囊泡与完整细胞和全细胞制备的膜囊泡进行比较,以建立脂质混合物与生命系统的模型膜。 第三个目标是使用分子动力学模拟来预测改进的耐受性膜改变脂质头基浓度,链饱和度,链分支,和麦角甾醇浓度。 将在体外测试具有改进的耐受性的膜,然后在工程化的S.酿酒酵母细胞

项目成果

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Laura Jarboe其他文献

Alkaline treatment for detoxification of acetic acid-rich pyrolytic bio-oil for microalgae fermentation: Effects of alkaline species and the detoxification mechanisms
  • DOI:
    10.1016/j.biombioe.2015.05.007
  • 发表时间:
    2015-09-01
  • 期刊:
  • 影响因子:
  • 作者:
    Xuefei Zhao;Kirsten Davis;Robert Brown;Laura Jarboe;Zhiyou Wen
  • 通讯作者:
    Zhiyou Wen

Laura Jarboe的其他文献

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{{ truncateString('Laura Jarboe', 18)}}的其他基金

RII Track-1: Building Capacity across Iowa to Meet Human Needs from Things that Grow
RII Track-1:在爱荷华州进行能力建设,以满足人类对生长物的需求
  • 批准号:
    2242763
  • 财政年份:
    2023
  • 资助金额:
    $ 19.97万
  • 项目类别:
    Cooperative Agreement
Planning: Planning Grant for EPSCOR Chemurgy 2.0 - Advanced Biomanufacturing for Next-Generation, Bio-inspired Products
规划:EPSCOR Chemurgy 2.0 规划拨款 - 下一代仿生产品的先进生物制造
  • 批准号:
    2207183
  • 财政年份:
    2022
  • 资助金额:
    $ 19.97万
  • 项目类别:
    Standard Grant
UNS: Engineering Stable Two- and Three-Component Bacterial Consortia
UNS:工程稳定的二组分和三组分细菌群落
  • 批准号:
    1511646
  • 财政年份:
    2015
  • 资助金额:
    $ 19.97万
  • 项目类别:
    Standard Grant
Biological Utilization of Thermolytic Substrates by Bacteria and Microalgae: Addressing Toxicity of Substrate Contaminants
细菌和微藻对热解底物的生物利用:解决底物污染物的毒性
  • 批准号:
    1133319
  • 财政年份:
    2012
  • 资助金额:
    $ 19.97万
  • 项目类别:
    Continuing Grant

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Cell Research
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    2007
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  • 项目类别:
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