Artificial metalloenzyme flips switch in cells

Abstract

By adding artificial metalloenzymes to cells, researchers can coax the cells to do a job they can’t normally do. Typically, that out-of-the-ordinary task is fairly simple, like uncaging a fluorescent reporter molecule. Swiss researchers, led by Thomas R. Ward of the University of Basel, Martin Fussenegger of ETH Zurich, and Stefan Matile of the University of Geneva, decided to take artificial metalloenzymes to the next level. Their synthetic enzyme uncages a molecule that then switches on a synthetic gene circuit inside cells (Nat. Commun. 2018, DOI: 10.1038/s41467-018-04440-0). Such an approach might one day allow researchers to use designer cells to produce protein therapeutics. The new metalloenzyme comprises three main components: the protein streptavidin, a ruthenium catalyst, and a cell-penetrating polymer. Streptavidin serves as a scaffold to which the researchers attach the catalyst and the polymer via biotin chemistry. The catalyst helps cleave, or uncage, a molecule containing an allyl-carbamate...