| 项目编号: | 1265044
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| 项目名称: | Spore-Based Designer Enzyme Cascade Biocatalysts |
| 作者: | Xin Ge
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| 承担单位: | University of California-Riverside
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| 批准年: | 2013
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| 开始日期: | 2014-04-15
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| 结束日期: | 2018-03-31
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| 资助金额: | USD364000
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | enzyme cascade
; enzyme
; enzyme catalyst
; nature
; cofactor
; modular designer biocatalyst platform
; enzyme catalytic process
; pharmaceutical
; designer biocatalyst
; surface
; efficient cofactor regeneration
; dehydrogenase
; oxidoreductase enzyme
; multienzyme complex
; expensive co-enzyme
; enzyme complex
; investigator
; catalyst
; enzyme system
|
| 英文摘要: | 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. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/97110
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| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
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| Recommended Citation: | |
Xin Ge. Spore-Based Designer Enzyme Cascade Biocatalysts. 2013-01-01.
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