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A Blueprint for a Synthetic Genetic Feedback Optimizer

Overview
Journal Nat Commun
Specialty Biology
Date 2023 May 3
PMID 37137895
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Abstract

Biomolecular control enables leveraging cells as biomanufacturing factories. Despite recent advancements, we currently lack genetically encoded modules that can be deployed to dynamically fine-tune and optimize cellular performance. Here, we address this shortcoming by presenting the blueprint of a genetic feedback module to optimize a broadly defined performance metric by adjusting the production and decay rate of a (set of) regulator species. We demonstrate that the optimizer can be implemented by combining available synthetic biology parts and components, and that it can be readily integrated with existing pathways and genetically encoded biosensors to ensure its successful deployment in a variety of settings. We further illustrate that the optimizer successfully locates and tracks the optimum in diverse contexts when relying on mass action kinetics-based dynamics and parameter values typical in Escherichia coli.

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References
1.
Borkowski O, Ceroni F, Stan G, Ellis T . Overloaded and stressed: whole-cell considerations for bacterial synthetic biology. Curr Opin Microbiol. 2016; 33:123-130. DOI: 10.1016/j.mib.2016.07.009. View

2.
Barkai N, Leibler S . Robustness in simple biochemical networks. Nature. 1997; 387(6636):913-7. DOI: 10.1038/43199. View

3.
Agrawal D, Marshall R, Noireaux V, Sontag E . In vitro implementation of robust gene regulation in a synthetic biomolecular integral controller. Nat Commun. 2019; 10(1):5760. PMC: 6917713. DOI: 10.1038/s41467-019-13626-z. View

4.
Lillacci G, Benenson Y, Khammash M . Synthetic control systems for high performance gene expression in mammalian cells. Nucleic Acids Res. 2018; 46(18):9855-9863. PMC: 6182142. DOI: 10.1093/nar/gky795. View

5.
Gyorgy A, Del Vecchio D . Modular composition of gene transcription networks. PLoS Comput Biol. 2014; 10(3):e1003486. PMC: 3952816. DOI: 10.1371/journal.pcbi.1003486. View