title: Towards Prebiotic Catalytic Amyloids Using High Throughput Screening.
abstract: Enzymes are capable of directing complex stereospecific transformations and of accelerating reaction rates many orders of magnitude. As even the simplest known enzymes comprise thousands of atoms, the question arises as to how such exquisite catalysts evolved. A logical predecessor would be shorter peptides, but they lack the defined structure and size that are apparently necessary for enzyme functions. However, some very short peptides are able to assemble into amyloids, thereby forming a well-defined tertiary structure called the cross-β-sheet, which bestows unique properties upon the peptides. We have hypothesized that amyloids could have been the catalytically active precursor to modern enzymes. To test this hypothesis, we designed an amyloid peptide library that could be screened for catalytic activity. Our approach, amenable to high-throughput methodologies, allowed us to find several peptides and peptide mixtures that form amyloids with esterase activity. These results indicate that amyloids, with their stability in a wide range of conditions and their potential as catalysts with low sequence specificity, would indeed be fitting precursors to modern enzymes. Furthermore, our approach can be efficiently expanded upon in library size, screening conditions, and target activity to yield novel amyloid catalysts with potential applications in aqueous-organic mixtures, at high temperature and in other extreme conditions that could be advantageous for industrial applications.
authors.affiliation: Laboratory of Physical Chemistry, Department of Chemistry, ETH Zürich, Zurich, Switzerland.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Friedmann
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, ETH Zürich, Zurich, Switzerland.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Torbeev
authors.affiliation: Laboratory of Physical Chemistry, Department of Chemistry, ETH Zürich, Zurich, Switzerland.
authors.forename: Viviane
authors.initials: V
authors.lastname: Zelenay
authors.affiliation: Laboratory of Physical Chemistry, Department of Chemistry, ETH Zürich, Zurich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sobol
authors.affiliation: Laboratory of Physical Chemistry, Department of Chemistry, ETH Zürich, Zurich, Switzerland.
authors.forename: Jason
authors.initials: J
authors.lastname: Greenwald
authors.affiliation: Laboratory of Physical Chemistry, Department of Chemistry, ETH Zürich, Zurich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Riek
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D002384:Catalysis; D002942:Circular Dichroism; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D006868:Hydrolysis; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000737:chemistry*; D056692:Prebiotics; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000682:Amyloid; D010446:Peptide Fragments; D056692:Prebiotics