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A cybergenetic framework for engineering intein-mediated integral feedback control systems.

Stanislav Anastassov¹, Maurice Filo¹, Ching-Hsiang Chang¹

¹Department of Biosystems Science and Engineering, ETH Zürich, 4058, Basel, Switzerland.

Nature Communications

|March 11, 2023

Summary

This summary is machine-generated.

Inteins are identified as versatile genetic components for creating Robust Perfect Adaptation (RPA) controllers. This study presents a systematic design approach and demonstrates their effective application in mammalian cells for biotechnology.

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Area of Science:

Biotechnology
Synthetic Biology
Molecular Systems Biology

Background:

Biological systems exhibit Robust Perfect Adaptation (RPA) to maintain stable internal states despite disturbances.
RPA is often achieved using biomolecular integral feedback controllers within cells.
These controllers have significant potential in biotechnology and therapeutic applications.

Purpose of the Study:

To identify inteins as suitable genetic components for implementing RPA controllers.
To develop a systematic design and modeling approach for intein-based RPA controllers.
To demonstrate the efficacy of engineered intein-based controllers in mammalian cells.

Main Methods:

Theoretical framework development for screening intein-based controllers.
Simplified modeling approaches for intein-based systems.
Genetic engineering and experimental testing of intein controllers with transcription factors in mammalian cells.

Main Results:

Inteins were identified as a versatile class of genetic components for RPA implementation.
A systematic design and modeling framework for intein-based controllers was established.
Engineered intein-based controllers demonstrated robust adaptation properties across a wide dynamic range in mammalian cells.

Conclusions:

Inteins offer a flexible and broadly applicable platform for constructing genetic RPA integral feedback control systems.
The developed approach enables the creation of diverse control systems for applications in metabolic engineering and cell-based therapy.
This work expands the toolkit for synthetic biology by providing a novel method for achieving precise biological regulation.