Expanding the viewpoint: Leveraging sequence information in enzymology

The use of protein sequence to inform enzymology in terms of structure, mechanism, and function has burgeoned over the past two decades. Referred to as genomic enzymology, the utilization of bioinformatic tools such as sequence similarity networks and phylogenetic analyses has allowed the identification of new substrates and metabolites, novel pathways, and unexpected reaction mechanisms. The holistic examination of superfamilies can yield insight into the origins and paths of evolution of enzymes and the range of their substrates and mechanisms. Herein, we highlight advances in the use of genomic enzymology to address problems which the in-depth analyses of a single enzyme alone could not enable.