In silico optimization of a guava antimicrobial peptide enables combinatorial exploration for peptide design

© 2018 The Author(s). Plants are extensively used in traditional medicine, and several plant antimicrobial peptides have been described as potential alternatives to conventional antibiotics. However, after more than four decades of research no plant antimicrobial peptide is currently used for treati...

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Bibliographic Details
Main Authors: Porto, William F, Irazazabal, Luz, Alves, Eliane SF, Ribeiro, Suzana M, Matos, Carolina O, Pires, Állan S, Fensterseifer, Isabel CM, Miranda, Vivian J, Haney, Evan F, Humblot, Vincent, Torres, Marcelo DT, Hancock, Robert EW, Liao, Luciano M, Ladram, Ali, Lu, Timothy K, de la Fuente-Nunez, Cesar, Franco, Octavio L
Other Authors: Massachusetts Institute of Technology. Synthetic Biology Center
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2021
Online Access:https://hdl.handle.net/1721.1/135014
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Summary:© 2018 The Author(s). Plants are extensively used in traditional medicine, and several plant antimicrobial peptides have been described as potential alternatives to conventional antibiotics. However, after more than four decades of research no plant antimicrobial peptide is currently used for treating bacterial infections, due to their length, post-translational modifications or high dose requirement for a therapeutic effect. Here we report the design of antimicrobial peptides derived from a guava glycine-rich peptide using a genetic algorithm. This approach yields guavanin peptides, arginine-rich α-helical peptides that possess an unusual hydrophobic counterpart mainly composed of tyrosine residues. Guavanin 2 is characterized as a prototype peptide in terms of structure and activity. Nuclear magnetic resonance analysis indicates that the peptide adopts an α-helical structure in hydrophobic environments. Guavanin 2 is bactericidal at low concentrations, causing membrane disruption and triggering hyperpolarization. This computational approach for the exploration of natural products could be used to design effective peptide antibiotics.