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

Okamoto, Yasunori
Kojima, Ryosuke
Schwizer, Fabian
Heinisch, Tillmann
Fussenegger, Martin
Ward, Thomas R.
Published in Nature Communications. 2018, vol. 9, no. 1, p. 1943
Abstract 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.
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Research group Groupe Matile
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OKAMOTO, Yasunori et al. A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell. In: Nature Communications, 2018, vol. 9, n° 1, p. 1943. doi: 10.1038/s41467-018-04440-0 https://archive-ouverte.unige.ch/unige:105117

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Deposited on : 2018-06-06

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