Lipopeptides from Bacillus Probiotics Can Target Transmembrane Receptors NOX4, EGFR, PDGFR, and OCTN2 Involved in Oxidative Stress and Oncogenesis

The mechanisms of action of probiotics at the molecular level remain an active subject of discussion and study. It is evident that the bioactive metabolites of probiotic strains exhibit not only antimicrobial and antifungal properties but also more subtle regulatory effects. Of particular interest are the anticancer effects of probiotics, with increasing data accumulating in recent years regarding this area. In this study, we have investigated one such potential mechanism. Bioactive peptides are characteristic of Bacillus strains, known for their probiotic capabilities in veterinary medicine and aquaculture, and were tested for their ability to interact with several key eukaryotic proteins involved in important intracellular signalling pathways. Short peptides such as bacillomycin, fengycin, and others obtained from Bacillus were selected for docking with the targets NOX4, EGFR, PDGFR, and OCTN2. Iturin D showed high binding energy values with NOX4 and PDGFR (−17.996 and −21.11 kcal/mol respectively), while fengycin showed even higher free binding energy with these receptors (−28.21 and −24.51 kcal/mol respectively), indicating its potential binding capability with these key receptors. Furthermore, fengycin was ranked second in binding energy with EGFR and OCTN2 (−21.97 and −24.35 kcal/mol respectively), and plipastatin showed the best results with EGFR (−21.34 kcal/mol) and was second-ranked with NOX4 and OCTN2 (−23.20 and −28.95 kcal/mol respectively).Overall, plipastatin and fengycin exhibited significant activity in binding with all receptors, making them promising candidates for further research as modulators of these receptors.