Sarah Everts explains how unusual peptides with pharmacological potential are amenable to engineering. This opens the possibility that the various antibiotic and otherwise bioactive lasso peptides that pathogenic bacteria produce might be tweaked to make drugs. The lasso fold was first described in 2003, when three groups simultaneously published reports about the unusual tertiary structure of a natural product called microcin J25. The team found that only six of 19 amino acids are required to attain capistruin's lasso fold, primarily near the seam of the macrolactam ring. Seven lasso peptides have been identified, some of which are reinforced by disulfide bonds. Because the lasso peptides were initially very hard to characterize, they are so strong that the peptides often do not break apart in mass spectrometers. Acquiring 3-D structures of the catalytic enzymes required to fold the lasso peptides would help scientists understand how the unique fold is achieved and also help those wishing to engineer novel lasso peptides.