Fussenegger, M.; Matile, S.; Ward, T.R.

Nat. Commun. 2018, 9, 10.1038/s41467-018-04440-0

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.

Bian, H.-D.; Liang, H.

Dalton Trans. 2016, 45, 8061-8072, 10.1039/C5DT04507J

An artificial metalloenzyme (BSA–CoL) based on the incorporation of a cobalt(ii) Schiff base complex {CoL, H2L = 2,2′-[(1,2-ethanediyl)bis(nitrilopropylidyne)]bisphenol} with bovine serum albumin (BSA) has been synthesized and characterized.