A Marine Brevibacillus-Derived Membrane-Lytic Peptide: Molecular Insight and Biophysical Characterization of a Novel AMP, FNL62-AMP.

This study characterizes the genomic identity, functional efficacy, and computational biophysics of FNL62-AMP, a novel antimicrobial peptide isolated from a phylogenomically distinct, newly identified Brevibacillus species. Production kinetics revealed a late-exponential phase onset of antibacterial activity with sustained potency against methicillin-resistant Staphylococcus aureus (MRSA). LC-MS/MS analysis identified the peptide sequence as NH2-LLLLFR-COOH. FNL62-AMP demonstrated excellent formulation resilience, retaining full anti-MRSA activity under high thermal stress (80 °C for 6 h) and showing robust resistance to generic trypsin and proteinase K proteolysis. Formulative co-incubation assays demonstrated charge-dependent compatibility, where nonionic Triton X-100 preserved baseline efficacy while ionic surfactants induced antagonism. In vitro time-kill kinetics, scanning electron microscopy, and SYTOX Green assays confirmed rapid, concentration-dependent bactericidal action driven by immediate membrane permeabilization. Molecular dynamics simulations successfully captured the spontaneous self-assembly of 64 FNL62-AMP monomers into a stable macro-aggregate. This consolidation process was quantitatively characterized by a simultaneous contraction in the radius of gyration (Rg), a sharp drop in solvent-accessible surface area (SASA), and a transitional plateau in mean squared displacement (MSD). Ultimately, the high thermal stability, structural resilience, and predictable surfactant compatibility of FNL62-AMP propose ways to be developed for lead optimization and druggability.