| 项目编号: | 1509202
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| 项目名称: | UNS: Novel metabolic engineering strategies for complex oligosaccharide synthesis |
| 作者: | Ruizhen Chen
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| 承担单位: | Georgia Tech Research Corporation
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| 批准年: | 2014
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| 开始日期: | 2015-06-15
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| 结束日期: | 2018-05-31
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| 资助金额: | USD300133
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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: | oligosaccharide synthesis
; synthesis
; oligosaccharide
; target oligosaccharide
; cost-effective synthesis
; ruizhen oligosaccharides
; oligosaccharide biosynthesis
; biochemical engineering program
; bioprocessing strategy
; novel metabolic engineering strategy
; current synthesis technology
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| 英文摘要: | 1509202
Chen, Ruizhen
Oligosaccharides are molecular recognition elements that play key roles in many vital biological processes such as cell growth and development,and host-pathogen interaction. Among many potential applications, oligosaccharides are particularly promising in diagnostics, vaccine, cancer therapy, prebiotics, and new antimicrobials. Unfortunately, these applications are hindered by the limited scalability and cost-effectiveness of current synthesis technologies. This project develops novel microbial biocatalysts for scalable and cost-effective synthesis of oligosaccharides. The success of this research will not only impact basic research efforts such as the understanding of glycan structure-function relationship, but also will impact broadly on their medical applications, including but not limited to diagnostic cancer diagnostics, vaccine development, prebiotics, and new antivirals.
The goal of this research is to develop novel metabolic engineering strategies for complex oligosaccharide synthesis. Oligosaccharide biosynthesis is particularly difficult due to (i) a high cellular energy demand; (ii) the necessity to engage multiple sugar molecules; (iii) the complexity of the biochemical reaction network. These challenges accentuate as the target oligosaccharide becomes bigger and more complex. To overcome these challenges, a cellobiose-based metabolism that exploits energy-efficient phosphorolysis will be established to meet the high demand of cellular energy for synthesis. Using cellobiose based metabolism allows glucose, the best energy source, to be used without triggering its repression on the uptake of other sugars, thus enabling engineered biocatalysts to access multiple sugars as they are needed. The complexity of the biochemical network necessary for oligosaccharide synthesis is further addressed by breaking a complex reaction network into several small modules that are designed to be sequentially executed. Each module is activated at a time and for a duration dictated by a target oligosaccharide. This approach allows microbial biocatalysts to devote cellular resources (ATP, glycosyltransferase enzymes, and precursor pools) to only one glycosidic bond formation at a time so that it performs each glycosylation step efficiently. The methods used will include the expression of specific enzymes involved in oligosaccharide synthesis and the application of optimized feeding and bioprocessing strategies during synthesis of the desired compounds.
This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/94400
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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: | |
Ruizhen Chen. UNS: Novel metabolic engineering strategies for complex oligosaccharide synthesis. 2014-01-01.
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