A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell

Okamoto, Yasunori and Kojima, Ryosuke and Schwizer, Fabian and Bartolami, Eline and Heinisch, Tillmann and Matile, Stefan and Fussenegger, Martin and Ward, Thomas R.. (2018) A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell. Nature Communications, 9. p. 1943.

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Complementing enzymes in their native environment with either homogeneous or heterogeneous catalysts is challenging due to the sea of functionalities present within a cell. To supplement these efforts, artificial metalloenzymes are drawing attention as they combine attractive features of both homogeneous catalysts and enzymes. Herein we show that such hybrid catalysts consisting of a metal cofactor, a cell-penetrating module, and a protein scaffold are taken up into HEK-293T cells where they catalyze the uncaging of a hormone. This bioorthogonal reaction causes the upregulation of a gene circuit, which in turn leads to the expression of a nanoluc-luciferase. Relying on the biotin-streptavidin technology, variation of the biotinylated ruthenium complex: the biotinylated cell-penetrating poly(disulfide) ratio can be combined with point mutations on streptavidin to optimize the catalytic uncaging of an allyl-carbamate-protected thyroid hormone triiodothyronine. These results demonstrate that artificial metalloenzymes offer highly modular tools to perform bioorthogonal catalysis in live HEK cells.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Bioanorganische Chemie (Ward)
UniBasel Contributors:Ward, Thomas R. R. and Okamoto, Yasunori and Schwizer, Fabian and Heinisch, Tillmann and Fussenegger, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Research
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Jul 2019 12:40
Deposited On:22 May 2019 10:52

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