| 项目编号: | 1511425
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| 项目名称: | UNS: Combining strain recombineering with molecular reporters and customized selections to overcome limitations in producing renewable hydrocarbons |
| 作者: | Patrick Cirino
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| 承担单位: | University of Houston
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| 批准年: | 2014
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| 开始日期: | 2015-08-01
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| 结束日期: | 2018-07-31
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| 资助金额: | USD300000
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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: | metabolic constraint
; same recombineered strain library
; molecular reporter
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| 英文摘要: | 1511425
Cirino, Patrick C.
The proposed research aims to take advantage of recent advances in genome engineering, gene sequencing, and high-throughput screening of genetic variants to isolate improved, genetically modified microorganisms. Unique combinations of genome modifications will be identified that allow engineered Escherichia coli to more efficiently convert abundant and renewable sugars derived from biomass into precursor metabolites and higher value chemical products, such as biofuels and building blocks for producing natural products. In addition to advancing understanding in sustainable biochemicals production, these research activities will yield new insights into metabolism and microbial physiology, thereby contributing broadly to many biology-related disciplines. Outreach and educational activities are also incorporated into the research plan.
Overcoming many coordinated metabolic constraints that limit microbial biochemical production requires a large number of genetic and epistatic modifications. This research plan aims to use customized, endogenous biosensors or molecular reporters to find strains from large combinatorial genome libraries with improved production of compounds not coupled to cell growth. The focus is on screening expression level libraries of many genes at once, to enhance production through pathways that consume acetyl-CoA and NADPH (mevalonate synthesis/mevalonate sensor), malonyl-CoA (triacetic acid lactone synthesis/TAL sensor), and NADPH (xylitol production/ NADPH sensor). The same recombineered strain libraries will be combined with uniquely designed genetic backgrounds to enable the use of selections to identify new combinations of genetic modifications that show relaxed redox-based regulation and enhanced flux through non-fermentative pathways. The targeted product molecules are directly linked to key branch points in central metabolism and precursor metabolites associated with a broad range of biochemicals. The wide variety of genomic libraries synthesized through this research will be made available to the scientific community, to be applied in selections/screens for other biosynthetic pathways of interest.
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/93910
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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: | |
Patrick Cirino. UNS: Combining strain recombineering with molecular reporters and customized selections to overcome limitations in producing renewable hydrocarbons. 2014-01-01.
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