Moving metals: How microbes deliver metal cofactors to metalloproteins

First row d-block metal ions serve as vital cofactors for numerous essential enzymes and are therefore required nutrients for all forms of life. Despite this requirement, excess free transition metals are toxic. Free metal ions participate in the production of noxious reactive oxygen species and mis-metalate metalloproteins, rendering enzymes catalytically inactive. Thus, bacteria require systems to ensure metalloproteins are properly loaded with cognate metal ions to maintain protein function, while avoiding metal-mediated cellular toxicity. In this perspective we summarize the current mechanistic understanding of bacterial metallocenter maturation with specific emphasis on metallochaperones; a group of specialized proteins that both shield metal ions from inadvertent reactions and distribute them to cognate target metalloproteins. We highlight several recent advances in the field that have implicated new classes of proteins in the distribution of metal ions within bacterial proteins, while speculating on the future of the field of bacterial metallobiology.