第二章 合成生物系统设计 1-4.pptVIP

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群体感应 除了研究比较普遍的在大肠杆菌中构建群体感应机制获得目标功能外,R.Weiss等通过在酿酒酵母中构建人工群体感应系统而将其研究扩展到了真核细胞中。从拟南芥(Arabidopsis thaliana)中获取的信号系统与天然的酵母磷酸化级联线路相连接控制工程化的基因开关。此系统实现了高度的模块化设计,考虑到对系统响应的测量和调控的需要,还对信号进行了必要的放大。 群体感应 细胞分裂素cytokinin Engineered cytokinin-based sender-receiver communication in yeast. Synthetic signaling pathways for sender and receiver cells. AtlPT4, which catalyzes isopentenylation of ATP, enables the sender to synthesized secrete IP to nearby receiver cells. When IP signal binds AtCRE1, AtCRE1-YDP1-SKN7 phosphorylation activates GFP expression from the SSRE promoter in receiver cells. Ming-Tang Chen. Artificial cell-cell communication in yeast Saccharomyces cerevisiae using signaling elements from Arabidopsis thaliana. Nature Biotechnology. 2005, 23: 1551 群体感应 The hypothesized function of QS. At low cell densities, a large proportion of the extracellular factors disperse before they can be used, and so their production provides little direct or indirect fitness benefit. At high cell densities, a much greater proportion of the extracellular public goods can be used. Consequently, the production of extracellular public goods is more efficient and beneficial at higher population densities. Sophie E. Darcha. Density-dependent fitness benefits in quorum-sensing bacterial populations. PNAS. 2012, 109: 8259-8263. 群体感应 The AI-2 QS mechanism in E. coli During cell growth, AI-2 is synthesized within the cell cytoplasm and transported out of the cell membrane of individual bacterial cells. As the cell density increases, more AI-2 is accumulated within the extra-cellular milieu until the AI-2 concentration reaches a critical ‘‘threshold’’ and at this point it is transported back into the cells. Sara Hooshangi. LsrR Quorum Sensing ‘‘Switch’’ Is Revealed by a Bottom-Up Approach. PLoS Computational Biology. 2011, 7: e1002172 群体感应 The three most common quorum-sensing strategies in Gram-negative and Gram-positive bacteria Leo Eberl. Mining quorum sensing regulated proteins – Role of bacteria

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