| 项目编号: | 1437775
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| 项目名称: | Investigation of terminal alkene formation by polyketide synthases and the application toward sustainable alpha-olefin production |
| 作者: | Jay Keasling
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| 承担单位: | University of California-Berkeley
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| 批准年: | 2013
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| 开始日期: | 2014-09-01
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| 结束日期: | 2018-04-30
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| 资助金额: | USD377146
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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: | alpha-olefin
; application
; sustainable production
; native olefin producer
; polyketide synthase
; terminal olefin
; terminal alkene
; related aromatic alkene
; short-chain olefin
; specific polyketide synthase
; terminal olefin-forming pks module
; olefinic compound
; chimeric synthase
; pivotal transformation
; biological production
; olefin formation
; specific terminal alkene production
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| 英文摘要: | Proposed Title: Characterization of specific polyketide synthases and application toward the biological production of highly-desirable, short-chain olefins.
Recent concerns as to the supply and cost of petroleum-based fuels and commodity chemicals have sparked an interest in creating alternative routes to these important hydrocarbon compounds. In particular the alpha-olefins, a class of compounds currently derived from petroleum, serve as precursors to many industrially produced plastics, short chain fatty acids, surfactants and recently have been touted as potential fuel alternatives. One potential route for synthesizing commodity and specialty chemicals is to engineer microorganisms to transform inexpensive, renewable sugars to desired products. Unfortunately, the scope of biological transformations available to generate differing chemical functional groups is lacking, thus limiting our ability to replace all petroleum-derived commodity chemicals. In an effort to produce this important set of chemicals, scientists at the University of California, Berkeley have identified enzyme components comprising a class of polyketide synthase (PKS) terminal modules known to generate alpha-olefins by way of a unique structural feature. Understanding the mechanism of this enigmatic reaction will pave the way for future enzyme biocatalyst design, in particular, new designer PKS assemblies for specific terminal alkene production. Studies and engineering efforts concerning the PKS modules will be executed under the supervision of the awardee, Prof. Jay D. Keasling (UC, Berkeley), by a diverse group of students from a wide range of socioeconomic and educational backgrounds. In particular, through the iCLEM program and partnership with the University of California, Berkeley Extension Program, Keasling and his group aim to involve high school and undergraduate students pursuing education outside the formal university requirements (e.g. through Associate Degrees and certificate programs) to gain valuable hands-on experience.
The goal of this proposal is to understand how these unique, conserved terminal sulfotransferase-thioesterase (ST-TE) didomains of PKS function to produce alpha-olefins. The specific project aims include 1) to characterize the overall substrate tolerance and fundamental kinetic parameters of four terminal olefin-forming PKS modules; 2) to perform an in-depth mechanistic analysis of the CurM TE to better understand this pivotal transformation; and 3) to use this information to guide the generation of two chimeric synthases for the sustainable production of C5 (pentene) and C6 (hexene) terminal olefins, as well as the related aromatic alkene, styrene. PKS proteins will be expressed in Escherichia coli or a native olefin producer, such as cyanobacteria Synechococcus PCC 7002. Aggregate results will be leveraged to design highly active catalysts specific for producing these olefinic compounds. Chimeric PKSs will be evaluated in both E. coli and Synechococcus PCC 7002 to better explore PKS activity and olefin formation in both natural and unnatural hosts. Definition of this this unique termination mechanism and application of the findings to create novel enzymes will provide a biological route to terminal alkenes, which may ultimately contain novel functional groups (e.g., halogens, amines, etc.) that can be used to create new cross-linkable polymers with altered properties, or compounds with improved fuel characteristics, all from low-cost renewable resources. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/95818
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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: | |
Jay Keasling. Investigation of terminal alkene formation by polyketide synthases and the application toward sustainable alpha-olefin production. 2013-01-01.
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