Spore-Based Designer Enzyme Cascade Biocatalysts

基于孢子的酶级联生物催化剂

基本信息

  • 批准号:
    1265044
  • 负责人:
  • 金额:
    $ 35.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-04-15 至 2018-03-31
  • 项目状态:
    已结题

项目摘要

Abstract: The creation of value-added products such as fine chemicals and pharmaceuticals by chemical transformations has resulted in significant improvements in the quality of life we have been enjoying. Many of these chemical transformation processes use catalysts. These catalysts may be inorganic or biological in nature. Enzyme catalysts would be widely utilized to perform these chemical transformation processes, as they frequently offer advantages of high yield, high selectivity, high product purity, along with operation at ambient temperature and pressure in aqueous environment at moderate pH. However, many biocatalytic reactions involve expensive co-enzymes or co-factors and their recycling is essential for the processes to be cost-effective. This turns out to be a difficult or expensive process step, thereby limiting the ability to gain the advantages of using enzyme catalysts. Principal investigators Xin Ge and Ashok Mulchandani from the University of California Riverside looked to cellular reactions in nature to develop an approach to circumvent this issue. Inspired by the substrate channeling phenomena seen in multi-enzyme cascades in nature for circumventing unfavorable thermodynamics and kinetics, the PIs will explore the development of a modular designer biocatalyst platform on the surface of spores, where enzyme cascade is spatially organized with tunable stoichiometry to achieve highly efficient cofactor regeneration. The enzyme system is easy to produce and reuse, and has high stability. The modular nature of the system will allow easy insertion of the genes of the desired enzymes and control of the stoichiometric ratios on the surface.This collaborative research project is significant as it will lead to development of a novel robust modular platform for designer biocatalysts to address the needs of chemicals and pharmaceuticals manufacturing. A number of applications are readily envisioned. The improved catalysts and processes will increase US technological competitiveness. Collectively, the benefits from this research will support efficient, economical and green engineering production of many fine chemicals and pharmaceuticals. In addition, the PIs plan activities which will develop a globally competitive and divergent STEM workforce through the increased participation of women and underrepresented minorities. UC Riverside is the minority serving institution with the largest Hispanic student population among all UC campuses. The investigators plan to hire minority graduate and undergraduate students as research assistants for this project. The investigators also plan new curriculum efforts and are collaborating with a local middle school to establish an interactive science program titled Bio- catalysis for clean fuels. Most oxidoreductase enzymes involved in specialty chemical synthesis utilize expensive pyridine nucleotides as cofactors for catalysis. These enzyme catalytic processes have shortcomings in terms of cofactor recycling that limit total turnover number and productivity yields. The goal of the proposed research is to develop a modular designer biocatalyst platform for highly efficient cofactor regeneration. Inspired by the substrate channeling phenomena observed in nature and other studies of engineered multienzyme cascades and mini-cellulosomes, the scaffoldin- cohesin - dockerin system will be used to build a spatially organized multienzyme complex designed for highly efficient cofactor regeneration. This enzyme complex will consist of proximally located producing and regenerating dehydrogenases in desired stoichiometry on a selected surface to allow channeling of oxidized cofactor from the producing dehydrogenase to the regenerating dehydrogenases and vice versa, solving the regeneration problems. Because of their formidable resistance to extremes of temperatures, pH, solvents, humidity and radiations, bacterial spores will serve as the surface display for the enzyme cascade. Various control and reference experiments will be carried out for the typical synthesis reaction of ketone reduction to alcohol, and the enzyme coupled regeneration of the cofactor will be demonstrated in both aqueous and nonaqueous media. Extensive characterization and catalytic performance assessments are planned by the PIs. This information will be published and available for investigators of other biocatalytic applications.
摘要:通过化学转化生产精细化学品和药品等增值产品,大大改善了我们的生活质量。这些化学转化过程中的许多使用催化剂。这些催化剂在性质上可以是无机的或生物的。酶催化剂将被广泛用于进行这些化学转化过程,因为它们经常提供高产率、高选择性、高产物纯度的优点,沿着在环境温度和压力下在中等pH的水环境中操作。然而,许多生物催化反应涉及昂贵的辅酶或辅因子,并且它们的回收对于过程是成本有效的是必不可少的。这证明是困难或昂贵的工艺步骤,从而限制了获得使用酶催化剂的优点的能力。来自加州大学滨江的首席研究员Xin Ge和Ashok Mulchandani研究了自然界中的细胞反应,以开发一种方法来规避这个问题。受自然界中多酶级联中的底物通道现象的启发,PI将探索在孢子表面开发模块化设计生物催化剂平台,其中酶级联在空间上以可调化学计量进行组织,以实现高效的辅因子再生。该酶体系易于生产和重复使用,稳定性高。该系统的模块化性质将允许所需酶的基因的容易插入和表面上的化学计量比的控制。这个合作研究项目是重要的,因为它将导致设计生物催化剂,以满足化学品和药物制造的需求,一个新的强大的模块化平台的发展。许多应用是容易设想的。改进的催化剂和工艺将提高美国的技术竞争力。总的来说,这项研究的好处将支持许多精细化学品和药物的高效,经济和绿色工程生产。此外,PI计划通过增加妇女和代表性不足的少数群体的参与来发展具有全球竞争力和多样化的STEM劳动力。加州大学滨江分校是少数族裔服务机构,拥有加州大学所有校区中最大的西班牙裔学生人口。研究人员计划聘请少数民族研究生和本科生作为该项目的研究助理。研究人员还计划新的课程,并与当地一所中学合作,建立一个名为清洁燃料生物催化的互动科学项目。大多数参与特殊化学合成的氧化还原酶利用昂贵的吡啶核苷酸作为催化辅因子。这些酶催化过程在辅因子再循环方面存在缺陷,限制了总周转数和生产率。该研究的目标是开发一种模块化设计的生物催化剂平台,用于高效的辅因子再生。受在自然界中观察到的底物通道现象以及工程化多酶级联和微型纤维素体的其他研究的启发,支架蛋白-粘附蛋白-锚定蛋白系统将用于构建设计用于高效辅因子再生的空间组织的多酶复合物。该酶复合物将由在所选表面上以所需化学计量的邻近定位的产生和再生脱氢酶组成,以允许氧化辅因子从产生脱氢酶通道化至再生脱氢酶,反之亦然,从而解决再生问题。由于它们对极端温度、pH值、溶剂、湿度和辐射具有强大的抵抗力,细菌孢子将作为酶级联的表面展示。各种控制和参考实验将进行酮还原成醇的典型合成反应,并将在水性和非水性介质中证明辅因子的酶偶联再生。PI计划进行广泛的表征和催化性能评估。这些信息将被公布,并提供给其他生物催化应用的研究人员。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Spore-displayed enzyme cascade with tunable stoichiometry
  • DOI:
    10.1002/btpr.2416
  • 发表时间:
    2017-03-01
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Chen, Long;Mulchandani, Ashok;Ge, Xin
  • 通讯作者:
    Ge, Xin
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Xin Ge其他文献

Expression, purification and characterization of a quinoprotein L-sorbose dehydrogenase from Ketogulonicigenium vulgare Y25
来自 Ketogulonicigenium v​​ulgare Y25 的醌蛋白 L-山梨糖脱氢酶的表达、纯化和表征
  • DOI:
    10.5897/ajmr12.2280
  • 发表时间:
    2013-06
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Xionghua Xiong;Xin Ge;Yan Zhao;Xiaodong Han;Jianhua Wang;Weicai Zhang
  • 通讯作者:
    Weicai Zhang
Complete Large-signal Stability Analysis of DC Distribution Network via Brayton-Moser’s Mixed Potential Theory
利用 Brayton-Moser 混合势理论完成直流配电网大信号稳定性分析
Correlation Between Size and Activity Enhancement of Recombinantly Assembled Cellulosomes
重组组装的纤维素体的尺寸和活性增强之间的相关性
Research on Historical Value Evaluation and Protection Strategies of Traditional Courtyards in Yulin Ancient City, Shaanxi Province, China
陕西省榆林古城传统庭院历史价值评价及保护策略研究
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Xin Ge;Yang Chen;Lu Wang;Yirui Chen
  • 通讯作者:
    Yirui Chen
Energy Efficiency Optimization: Joint Antenna-Subcarrier-Power Allocation in OFDM-DASs
能效优化: OFDM-DAS 中的联合天线-子载波功率分配

Xin Ge的其他文献

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{{ truncateString('Xin Ge', 18)}}的其他基金

CAREER: Generation of Highly Selective Inhibitory Antibodies by Novel Paratope Design, Function-Based Screening, and Deep Sequencing
职业:通过新型互补位设计、基于功能的筛选和深度测序生成高选择性抑制抗体
  • 批准号:
    1453645
  • 财政年份:
    2015
  • 资助金额:
    $ 35.2万
  • 项目类别:
    Standard Grant

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