Synchronized DNA cycling across a bacterial population
Synchronized DNA cycling across a bacterial population
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DOI：
10.1038/ng.3915
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发表时间：
2017-08-01
期刊：
影响因子：
30.8
通讯作者：
Hasty, Jeff
中科院分区：
文献类型：
--
作者：
Baumgart, Leo;Mather, William;Hasty, Jeff
合成生物学的一个决定性目标是设计细胞来协调经常需要精确的基因表达时间调制的任务。尽管已经构建了各种相对较小的基因电路并对其进行了表征，但它们在更大网络中的逻辑组合仍然是一个核心挑战。这主要是由于缺乏可预测的动态基因表达控制的兼容和正交元素。作为启动子水平调控的另一种方法，我们探索了DNA拷贝数作为电路控制元件的使用。我们通过一种易于与其他基因电路一起使用的模块化设计，在大肠杆菌中以质粒拷贝数振荡的形式设计了菌落范围的DNA循环。拷贝数调制是一种可推广的原理，它为合成的基因电路增加了一层控制，允许动态调节电路元件，而不需要专门设计的启动子。
A defining goal of synthetic biology is to engineer cells to coordinate tasks that often require precise temporal modulation of gene expression. Although a variety of relatively small gene circuits have been constructed and characterized, their logical combination into larger networks remains a central challenge. This is due primarily to the lack of compatible and orthogonal elements for predictable dynamic control of gene expression. As an alternative approach to promoter-level regulation, we explored the use of DNA copy number as a circuit control element. We engineered colony-wide DNA cycling in Escherichia coli in the form of plasmid copy number oscillations via a modular design that can be readily adapted for use with other gene circuitry. Copy number modulation is a generalizable principle that adds a layer of control to synthetic gene circuits, allowing dynamic regulation of circuit elements without requiring specially engineered promoters.