A new study supports the hypothesis that the earliest enzymes may have been self-assembling peptides instead of full-length proteins. Ivan V. Korendovych of Syracuse University; William F. DeGrado of the University of California, San Francisco; and coworkers designed short peptides that self-assemble into catalytic amyloids (Nat. Chem. 2014, DOI: 10.1038/nchem.1894). Similar peptide aggregates are a hallmark of diseases such as Alzheimer’s. In this case, the amyloids are made of seven-residue peptides consisting of alternating apolar and polar residues. Leucines provide the hydrophobicity needed to drive amyloid formation; two histidines bind zinc ions, which stabilize the amyloid structure and allow it to catalyze acyl ester hydrolysis. “The study strengthens the hypothesis that amyloids played an important role in the origin of life,” says Roland Riek, a chemist at ETH Zurich who is studying functional amyloids and establishing amyloid structure-function relationships. In addition, says David S. Eisenberg, a chemist at UCLA who studies amyloid structure and formation, the work adds support to one of the hypotheses for the toxic effects of some amyloid fibers: that such fibers bind metals and as a result produce harmful reactive oxygen species.