Transcriptional programming using engineered systems of transcription factors and genetic architectures
Transcriptional programming using engineered systems of transcription factors and genetic architectures
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DOI：
10.1038/s41467-019-12706-4
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发表时间：
2019-10-21
影响因子：
16.6
通讯作者：
Wilson, Corey J.
中科院分区：
文献类型：
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作者：
Rondon, Ronald E.;Groseclose, Thomas M.;Wilson, Corey J.
基因表达的控制是代谢工程、合成基因网络设计和蛋白质制造的重要工具。迄今为止，最成功的方法是通过诱导偶联转录效应物来调节mRNA合成。在这里，我们提出了一种利用工程转录因子和互补遗传结构系统的生物编程结构。我们使用模块化设计策略创建27个非天然和非同义转录因子使用乳糖阻遏物拓扑作为指导。为了指导工程转录因子系统，我们采用平行和串联遗传（DNA）结构，并赋予基因表达的基本和组合逻辑控制。在这里，除了两个非规范的半与操作之外，我们还实现了AND、OR、NOT和NOR逻辑控制。基本的逻辑运算和相应的并行和串联遗传结构代表了后续组合程序的构建块，它同时显示数字和模拟性能。
The control of gene expression is an important tool for metabolic engineering, the design of synthetic gene networks, and protein manufacturing. The most successful approaches to date are based on modulating mRNA synthesis via an inducible coupling to transcriptional effectors. Here we present a biological programming structure that leverages a system of engineered transcription factors and complementary genetic architectures. We use a modular design strategy to create 27 non-natural and non-synonymous transcription factors using the lactose repressor topology as a guide. To direct systems of engineered transcription factors we employ parallel and series genetic (DNA) architectures and confer fundamental and combinatorial logical control over gene expression. Here we achieve AND, OR, NOT, and NOR logical controls in addition to two non-canonical half-AND operations. The basic logical operations and corresponding parallel and series genetic architectures represent the building blocks for subsequent combinatorial programs, which display both digital and analog performance.