Abstract
Synthetic biology is an emerging discipline, offering new perspectives in many industrial fields, from pharma and row-material production to renewable energy. Developing synthetic biology applications is often a lengthy and expensive process with extensive and tedious trial-and-error runs. Computational models can direct the engineering of biological circuits in a computer-aided design setting. By providing a virtual lab environment, in silico models of synthetic circuits can contribute to a quantitative understanding of the underlying molecular pathways before a wet-lab implementation. Here, we illustrate this notion from the point of view of signal fidelity and noise relationship. Noise in gene expression can undermine signal fidelity with implications on the well-functioning of the engineered organisms. For our analysis, we use a specific biological circuit that regulates the gene expression in bacterial inorganic phosphate economy. Applications that use this circuit include those in pollutant detection and wastewater treatment. We provide computational models with different levels of molecular detail as virtual labs. We show that inherent fluctuations in the gene expression machinery can be predicted via stochastic simulations to introduce control in the synthetic promoter design process. Our analysis suggests that noise in the system can be alleviated by strong synthetic promoters with slow unbinding rates. Overall, we provide a recipe for the computer-aided design of synthetic promoter libraries with specific signal to noise characteristics.