A cybergenetic framework for engineering intein-mediated integral feedback control systems
Open access
Date
2023Type
- Journal Article
Abstract
The ability of biological systems to tightly regulate targeted variables, despite external and internal disturbances, is known as Robust Perfect Adaptation (RPA). Achieved frequently through biomolecular integral feedback controllers at the cellular level, RPA has important implications for biotechnology and its various applications. In this study, we identify inteins as a versatile class of genetic components suitable for implementing these controllers and present a systematic approach for their design. We develop a theoretical foundation for screening intein-based RPA-achieving controllers and a simplified approach for modeling them. We then genetically engineer and test intein-based controllers using commonly used transcription factors in mammalian cells and demonstrate their exceptional adaptation properties over a wide dynamic range. The small size, flexibility, and applicability of inteins across life forms allow us to create a diversity of genetic RPA-achieving integral feedback control systems that can be used in various applications, including metabolic engineering and cell-based therapy. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000604962Publication status
publishedExternal links
Journal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
NatureOrganisational unit
03921 - Khammash, Mustafa / Khammash, Mustafa
Funding
743269 - Theory and Design tools for bio-molecular control systems (EC)
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