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The challenges associated with growing antimicrobial resistance are driving the search for effective and safe therapeutic innovations. In this scenario, natural products from plants and foods have emerged as promising sources of bioactive molecules. Acrocomia aculeata (Jacq.; Lodd. ex Mart.) is a palm tree native to Brazil, popularly known as bocaiuva, which has recognized nutritional and pharmacological effectiveness. Since the bocaiuva pulp oil showed no antimicrobial activity, we employed a bioinspired rational design approach. Using the DII protein from A. aculeata as a structural template, we designed a novel synthetic peptide (Acro-18) and investigated its antimicrobial activity and possible mechanisms of action Sequences were generated (CAMPr3) and selected based on antimicrobial activity prediction (Support Vector Machine and Random Forest). Physicochemical parameters (APD3), stability of the three-dimensional structure (I-TASSER, PROCHECK), model quality (ProSa-web), prediction of antimicrobial activity (DBAASP and ClassAMP), and homology with the original sequence were evaluated. The antimicrobial activity of the peptide was evaluated with minimum inhibitory concentration and bactericidal assays, by the broth microdilution method, against the strains of health and food importance (ATCC) E. faecalis (29212), S. aureus (29213), S. aureus MRSA (43300), K. pneumoniae (700603), A. baumannii (19906), P. aeruginosa (27853), E. aerogenes (13048), E. coli (35218), S. enterica (51741) and B. cereus (11778), starting at a concentration of 64 µM and followed by serial dilution. The membrane permeability assay was performed with Sytox™ Green in Gram-positive (S. aureus MRSA) and Gram-negative (E. coli) bacteria. The results demonstrated that the Acro-18 peptide has a Z-score of -1.83, a total charge of +6.25, 50% hydrophobicity, a Bowman index of 3.41 kcal/mol, and 72.2% homology to the original sequence. It was effective in inhibiting and eradicating the growth of the tested bacteria at concentrations ranging from 0.5 to 16 µM, and both types of bacteria were stained with the intercalating dye Sytox™ Green. The results suggest that the Acro-18 peptide has structural characteristics compatible with biological activity, confirmed by its effectiveness in combating bacteria. Its positive charge and hydrophobic balance may favor interaction with bacterial cell membranes, as confirmed by the results of the membrane permeability assay, which indicated a possible mechanism of action through damage to the bacterial plasma membrane. It is concluded that the Acro-18 peptide, bioinspired by A. aculeata, has high therapeutic potential and is a promising candidate for future applications in functional foods with antimicrobial properties.
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