The number of protein sequences found in genome-sequencing studies continues to grow, but the ability to decipher the functions of the corresponding proteins has not kept pace. Characterizing more enzymes and other proteins identified in sequencing projects could lead to the industrial use of new enzymes and pathways and better define nature’s metabolic repertoire. Researchers from two multidisciplinary programs, the Enzyme Function Initiative and the New York Structural Genomics Research Consortium, have now developed a new approach for defining protein function in which bacterial solute-binding proteins (SBPs) are screened against tailored chemical libraries or even entire metabolomes (Biochemistry 2014, DOI: 10.1021/bi501388y). SBPs grab small molecules outside bacterial cells that are initial reactants for metabolic pathways and shepherd them through cell membranes and into the cytosol. The study defined ligand-binding preferences for more than 2,000 SBPs and found numerous metabolic pathways. “These efforts begin to define an integrated strategy for realizing the full value of amassing genome sequence data,” the researchers note.