Natural and synthetic selenoproteins

•Selenocysteine endows proteins with novel redox properties.•New recombinant and chemical methods are facilitating selenoprotein production.•Many natural selenoproteins enhance protein folding and quality control in the ER.•Selenopeptides/proteins are useful tools for oxidative protein folding in vitro.

Once considered highly toxic, the element selenium is now recognized as a micronutrient essential for human health. It is inserted co-translationally into many proteins as the non-canonical amino acid selenocysteine, providing the resulting selenoprotein molecules with a range of valuable redox properties; selenocysteine is also increasingly exploited as a structural and mechanistic probe in synthetic peptides and proteins. Here we review topical investigations into the preparation and characterization of natural and artificial selenoproteins. Such molecules are uniquely suited as tools for protein chemistry and as a test bed for studying novel catalytic activities.