| 项目编号: | 1546790
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| 项目名称: | EAGER: Novel biocatalysts based on artificial metallo-cofactors in flavoproteins |
| 作者: | Stefan Lutz
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| 承担单位: | Emory University
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| 批准年: | 2014
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| 开始日期: | 2015-09-01
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| 结束日期: | 2017-08-31
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| 资助金额: | USD117715
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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
; new artificial biocatalyst
; flavoprotein
; pi
; active site
; artificial cofactor
; active cofactor site
|
| 英文摘要: | Lutz (1546790)
The proposed work will generate proof-of-concept data on re-engineering the active site of the flavoprotein, Old Yellow Enzyme (OYE), to perform hydrocarbon chemistry aimed at producing chemicals that are difficult to synthesize by non-biological approaches. To this end, the proposal will focus on creating new artificial biocatalysts by integrating catalytically active organometallic complexes in the active cofactor site in the interior of the enzyme. The new biocatalysts so-formed will be assessed for their potential to catalyze C-C bond forming reactions. Moreover, the general approach of substituting artificial prosthetic co-factors has potential for general applicability to many areas of chemical synthesis and chemical conversion to useful products. The project will also feature educational components to train students in the diverse engineering and scientific disciplines required for success in the bioengineering area, and will continue the principal investigator's (PI's) involvement in a number of programs aimed at increasing interest and education in STEM areas amongst underrepresented minorities in the greater Atlanta area.
The proposal capitalizes on the utility of flavin-dependent oxidoreductases as enzymes capable of biocatalysis at the laboratory scale. Specifically, the PI and his students will create new artificial biocatalysts by integrating catalytically efficient copper-bis(oxazoline)(Cu-BOX) complexes in the active site of Old Yellow Enzyme. Although challenging, the PI is well positioned to carry out this synthesis successfully based on more than three years of work in his lab on OYE which has already demonstrated substantial improvements in the enzyme's native redox activity. These studies have confirmed the PI's capability to make substantial changes in the active site without compromising the overall structural integrity of the enzyme. The modified enzymes will then be tested for catalytic activity via asymmetric cyclopropanation of styrene and ethyl diazoacetate, a benchmark reaction for C-C bond formation. By exploring new possibilities for the flavoprotein, the incorporation of artificial cofactors based on organo-metallic ligands could dramatically expand the toolbox for biocatalysis. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/93448
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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: | |
Stefan Lutz. EAGER: Novel biocatalysts based on artificial metallo-cofactors in flavoproteins. 2014-01-01.
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