A blueprint for a synthetic genetic feedback optimizer

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...

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Bibliographic Details
Published in:Nature communications 2023-05, Vol.14 (1), p.2554-2554, Article 2554
Main Authors: Gyorgy, Andras, Menezes, Amor, Arcak, Murat
Format: Article
Language:English
Subjects:
631/114/2397
631/61/338/552
639/166/985
Biology
Biosensors
Decay rate
E coli
Feedback
Gene Regulatory Networks
Genetic code
Humanities and Social Sciences
Modules
multidisciplinary
Optimization
Parameter sensitivity
Perturbation
Science
Science (multidisciplinary)
Synthetic Biology
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Summary: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 . Genetic modules are sensitive to changes in their context and to environmental perturbations. Here, the authors develop a genetic optimizer based on common synthetic biology parts to ensure optimal and robust cellular performance in diverse contexts.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-37903-0