Chemical Zymogens and Transmembrane Activation of Transcription in Synthetic Cells

Dante Guldbrandsen Andersen; Andreas Bøtker Pedersen; Martin Høgholm Jørgensen; Mireia Casanovas Montasell; Ane Bretschneider Søgaard; Gal Chen; Avi Schroeder; Gregers Rom Andersen; Alexander N Zelikin

doi:10.1002/adma.202309385

Chemical Zymogens and Transmembrane Activation of Transcription in Synthetic Cells

Dante Guldbrandsen Andersen, Andreas Bøtker Pedersen, Martin Høgholm Jørgensen, Mireia Casanovas Montasell, Ane Bretschneider Søgaard, Gal Chen, Avi Schroeder, Gregers Rom Andersen, Alexander N Zelikin^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

5 Citations (Scopus)

Abstract

In this work, synthetic cells equipped with an artificial signaling pathway that connects an extracellular trigger event to the activation of intracellular transcription are engineered. Learning from nature, this is done via an engineering of responsive enzymes, such that activation of enzymatic activity can be triggered by an external biochemical stimulus. Reversibly deactivated creatine kinase to achieve triggered production of adenosine triphosphate, and a reversibly deactivated nucleic acid polymerase for on-demand synthesis of RNA are engineered. An extracellular, enzyme-activated production of a diffusible zymogen activator is also designed. The key achievement of this work is that the importance of cellularity is illustrated whereby the separation of biochemical partners is essential to resolve their incompatibility, to enable transcription within the confines of a synthetic cell. The herein designed biochemical pathway and the engineered synthetic cells are arguably primitive compared to their natural counterpart. Nevertheless, the results present a significant step toward the design of synthetic cells with responsive behavior, en route from abiotic to life-like cell mimics.

Original language	English
Article number	2309385
Journal	Advanced Materials
Volume	36
Issue	6
Number of pages	10
ISSN	0935-9648
DOIs	https://doi.org/10.1002/adma.202309385
Publication status	Published - 2024

Keywords

chemical zymogen
enzyme activation
synthetic cells
transcription

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10.1002/adma.202309385

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abstract = "In this work, synthetic cells equipped with an artificial signaling pathway that connects an extracellular trigger event to the activation of intracellular transcription are engineered. Learning from nature, this is done via an engineering of responsive enzymes, such that activation of enzymatic activity can be triggered by an external biochemical stimulus. Reversibly deactivated creatine kinase to achieve triggered production of adenosine triphosphate, and a reversibly deactivated nucleic acid polymerase for on-demand synthesis of RNA are engineered. An extracellular, enzyme-activated production of a diffusible zymogen activator is also designed. The key achievement of this work is that the importance of cellularity is illustrated whereby the separation of biochemical partners is essential to resolve their incompatibility, to enable transcription within the confines of a synthetic cell. The herein designed biochemical pathway and the engineered synthetic cells are arguably primitive compared to their natural counterpart. Nevertheless, the results present a significant step toward the design of synthetic cells with responsive behavior, en route from abiotic to life-like cell mimics.",

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language = "English",

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journal = "Advanced Materials",

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Chemical Zymogens and Transmembrane Activation of Transcription in Synthetic Cells. / Andersen, Dante Guldbrandsen; Pedersen, Andreas Bøtker; Jørgensen, Martin Høgholm et al.
In: Advanced Materials, Vol. 36, No. 6, 2309385, 2024.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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T1 - Chemical Zymogens and Transmembrane Activation of Transcription in Synthetic Cells

AU - Andersen, Dante Guldbrandsen

AU - Pedersen, Andreas Bøtker

AU - Jørgensen, Martin Høgholm

AU - Montasell, Mireia Casanovas

AU - Søgaard, Ane Bretschneider

AU - Chen, Gal

AU - Schroeder, Avi

AU - Andersen, Gregers Rom

AU - Zelikin, Alexander N

PY - 2024

Y1 - 2024

N2 - In this work, synthetic cells equipped with an artificial signaling pathway that connects an extracellular trigger event to the activation of intracellular transcription are engineered. Learning from nature, this is done via an engineering of responsive enzymes, such that activation of enzymatic activity can be triggered by an external biochemical stimulus. Reversibly deactivated creatine kinase to achieve triggered production of adenosine triphosphate, and a reversibly deactivated nucleic acid polymerase for on-demand synthesis of RNA are engineered. An extracellular, enzyme-activated production of a diffusible zymogen activator is also designed. The key achievement of this work is that the importance of cellularity is illustrated whereby the separation of biochemical partners is essential to resolve their incompatibility, to enable transcription within the confines of a synthetic cell. The herein designed biochemical pathway and the engineered synthetic cells are arguably primitive compared to their natural counterpart. Nevertheless, the results present a significant step toward the design of synthetic cells with responsive behavior, en route from abiotic to life-like cell mimics.

AB - In this work, synthetic cells equipped with an artificial signaling pathway that connects an extracellular trigger event to the activation of intracellular transcription are engineered. Learning from nature, this is done via an engineering of responsive enzymes, such that activation of enzymatic activity can be triggered by an external biochemical stimulus. Reversibly deactivated creatine kinase to achieve triggered production of adenosine triphosphate, and a reversibly deactivated nucleic acid polymerase for on-demand synthesis of RNA are engineered. An extracellular, enzyme-activated production of a diffusible zymogen activator is also designed. The key achievement of this work is that the importance of cellularity is illustrated whereby the separation of biochemical partners is essential to resolve their incompatibility, to enable transcription within the confines of a synthetic cell. The herein designed biochemical pathway and the engineered synthetic cells are arguably primitive compared to their natural counterpart. Nevertheless, the results present a significant step toward the design of synthetic cells with responsive behavior, en route from abiotic to life-like cell mimics.

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Chemical Zymogens and Transmembrane Activation of Transcription in Synthetic Cells

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Keywords

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