Predicting Transcriptional Output of Synthetic Multi-input Promoters,ACS Synthetic Biology

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Predicting Transcriptional Output of Synthetic Multi-input Promoters
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-07-24 00:00:00 , DOI: 10.1021/acssynbio.8b00165
David M. Zong , Selahittin Cinar ₁ , David L. Shis , Krešimir Josić ₁ , William Ott ₁ , Matthew R. Bennett

Affiliation

Recent advances in synthetic biology have led to a wealth of well-characterized genetic parts. As parts libraries grow, so too does the potential to create novel multi-input promoters that integrate disparate signals to determine transcriptional output. Our ability to construct such promoters will outpace our ability to characterize promoter performance, due to the vast number of input combinations. In this study, we examine the input–output relations of recently developed synthetic multi-input promoters and describe two methods for predicting their behavior. The first method uses 1-dimensional induction data obtained from experiments on single-input systems to predict the n-dimensional induction responses of systems with n inputs. We demonstrate that this approach accurately predicts Boolean (on/off) responses of multi-input systems consisting of novel chimeric transcription factors and hybrid promoters in Escherichia coli. The second method uses only a small amount of multi-input response data to accurately predict analog system response over the entire landscape of input combinations. Taken together, these methods facilitate the design of synthetic circuits that utilize multi-input promoters.

中文翻译：

预测合成多输入启动子的转录输出

合成生物学的最新进展导致了许多特征明确的遗传部分。随着零件库的增长，创建新颖的多输入启动子的潜力也在增加，这些启动子整合了不同的信号以确定转录输出。由于大量的输入组合，我们构建此类启动子的能力将超过我们表征启动子性能的能力。在这项研究中，我们研究了最近开发的合成多输入启动子的输入-输出关系，并描述了两种预测其行为的方法。第一种方法使用从在单输入系统实验中获得的一维感应数据来预测Ñ与系统维感应响应Ñ输入。我们证明了这种方法可以准确预测由新型嵌合转录因子和大肠杆菌中的杂种启动子组成的多输入系统的布尔（开/关）响应。第二种方法仅使用少量的多输入响应数据来准确预测整个输入组合情况下的模拟系统响应。总之，这些方法有助于设计利用多输入启动子的合成电路。

更新日期：2018-07-24

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