Automated Design of Genetic Toggle Switches with Predetermined Bistability

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• 作者：Shuobing Chen ; Haoqian Zhang ; Handuo Shi ; Weiyue Ji ; Jingchen Feng ; Yan Gong ; Zhenglin Yang ; Qi Ouyang
• 刊名：ACS Synthetic Biology
• 出版年：2012
• 出版时间：July 20, 2012
• 年：2012
• 卷：1
• 期：7
• 页码：284-290
• 全文大小：404K
• 年卷期：v.1,no.7(July 20, 2012)
• ISSN：2161-5063

文摘

Synthetic biology aims to rationally construct biological devices with required functionalities. Methods that automate the design of genetic devices without post-hoc adjustment are therefore highly desired. Here we provide a method to predictably design genetic toggle switches with predetermined bistability. To accomplish this task, a biophysical model that links ribosome binding site (RBS) DNA sequence to toggle switch bistability was first developed by integrating a stochastic model with RBS design method. Then, to parametrize the model, a library of genetic toggle switch mutants was experimentally built, followed by establishing the equivalence between RBS DNA sequences and switch bistability. To test this equivalence, RBS nucleotide sequences for different specified bistabilities were in silico designed and experimentally verified. Results show that the deciphered equivalence is highly predictive for the toggle switch design with predetermined bistability. This method can be generalized to quantitative design of other probabilistic genetic devices in synthetic biology.

Keywords:

genetic toggle switch; RBS calculator; rational design; stochastic model