Programming the Dynamic Control of Bacterial Gene Expression with a Chimeric Ligand- and Light-Based Promoter System,ACS Synthetic Biology

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Programming the Dynamic Control of Bacterial Gene Expression with a Chimeric Ligand- and Light-Based Promoter System
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-10-25 00:00:00 , DOI: 10.1021/acssynbio.8b00280
Premkumar Jayaraman _{1,

2} , Jing Wui Yeoh _{1,

2} , Jingyun Zhang _{1,

2} , Chueh Loo Poh _{1,

2}

Affiliation

To program cells in a dynamic manner, synthetic biologists require precise control over the threshold levels and timing of gene expression. However, in practice, modulating gene expression is widely carried out using prototypical ligand-inducible promoters, which have limited tunability and spatiotemporal resolution. Here, we built two dual-input hybrid promoters, each retaining the function of the ligand-inducible promoter while being enhanced with a blue-light-switchable tuning knob. Using the new promoters, we show that both ligand and light inputs can be synchronously modulated to achieve desired amplitude or independently regulated to generate desired frequency at a specific amplitude. We exploit the versatile programmability and orthogonality of the two promoters to build the first reprogrammable logic gene circuit capable of reconfiguring into logic OR and N-IMPLY logic on the fly in both space and time without the need to modify the circuit. Overall, we demonstrate concentration- and time-based combinatorial regulation in live bacterial cells with potential applications in biotechnology and synthetic biology.

中文翻译：

用基于嵌合体和光的启动子系统对细菌基因表达的动态控制进行编程

为了以动态方式对细胞进行编程，合成生物学家需要精确控制基因表达的阈值水平和时间。但是，实际上，调节基因表达是使用原型配体诱导型启动子广泛进行的，其具有有限的可调性和时空分辨率。在这里，我们构建了两个双输入杂交启动子，每个启动子都保留了配体诱导型启动子的功能，同时通过可蓝光切换的调节旋钮进行了增强。使用新的启动子，我们表明配体和光输入都可以同步调制以达到所需的振幅，也可以独立调节以产生特定振幅的所需频率。我们利用两个启动子的通用可编程性和正交性来构建第一个可重编程的逻辑基因电路，该电路能够在时空上快速配置为逻辑OR和N-IMPLY逻辑，而无需修改电路。总的来说，我们证明了活细菌细胞中基于浓度和时间的组合调控，并在生物技术和合成生物学中具有潜在的应用。

更新日期：2018-10-25

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