Chemical Zymogens and Transmembrane Activation of Transcription in Synthetic Cells.

Autor: Andersen DG; iNano Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, 8000, Denmark., Pedersen AB; Department of Chemistry, Aarhus University, Aarhus, 8000, Denmark., Jørgensen MH; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, 8000, Denmark., Montasell MC; Department of Chemistry, Aarhus University, Aarhus, 8000, Denmark., Søgaard AB; iNano Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, 8000, Denmark., Chen G; Department of Chemical Engineering, Technion, Haifa, 32000, Israel., Schroeder A; Department of Chemical Engineering, Technion, Haifa, 32000, Israel., Andersen GR; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, 8000, Denmark., Zelikin AN; iNano Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, 8000, Denmark.; Department of Chemistry, Aarhus University, Aarhus, 8000, Denmark.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2024 Feb; Vol. 36 (6), pp. e2309385. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1002/adma.202309385
Abstrakt: 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.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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