Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Catalytic Amyloids Promote Carbon Dioxide Hydration with Efficiencies that Rival those of Native Carbonic Anhydrases.   (123680)

Ivan Korendovych 1
  1. Baylor University, Waco, TX, United States

Previously we have shown that short de novo designed peptides can self-assemble into highly reactive amyloid-like catalysts for hydrolysis of activated esters [1]. Subsequent work by many groups showed broad applicability of this approach to many different model transformations [2]. Here we set out to explore whether catalytic amyloids can replicate native activities of enzymes. We have rationally designed a series 9-residue peptides that self-assemble in the presence of zinc to promote CO2 hydration with kcat/KM of 1.2 x 106 M-1s-1. The specific activity of the assemblies is at least 100-fold faster than any reported to date artificial catalysts of CO2 hydration and are on par with those of natural carbonic anhydrases. To our knowledge this is the first example of a model system capable of achieving enzymatic levels of activities for the reactions important in nature. This is even more exciting considering that the functional complexity needed to promote efficient catalysis was achieved by supramolecular self-assembly of short peptides containing only natural amino acid residues. Unlike enzymes, catalytic amyloids are extremely robust and can be used under harsh conditions to help promote CO2 capture and fixation.

  1. [1] Rufo, C.M., Moroz, Y.S., Moroz, O.M., Stoehr, J., Smith T.A., Hu, Z., DeGrado, W.F., Korendovych, I.V. (2014) Short peptides self-assemble to produce catalytic amyloids, Nat. Chem. 6:303-309, http://doi.org/10.1038/nchem.1894
  2. [2] Zozulia, O., Dolan, M.A., Korendovych, I.V. (2018) Catalytic peptide assemblies, Chem. Soc. Rev. 47:3621-3639, http://doi.org/10.1039/C8CS00080H