Menaquinone is an emerging target for antimicrobial peptides. Could it be the new Achilles’ Heel of bacteria?

The rise of antibiotic resistance threatens to undermine modern medicine, making the development of new antibiotics and novel targets an urgent priority. Among emerging strategies, targeting menaquinone (MK), a membrane-bound electron carrier, has gained traction as a promising yet underexplored approach. MK is only used for electron transport in bacteria, making it an attractive, selective antimicrobial target. Since the discovery of the first MK-binding antimicrobial peptide (MBAMP), lysocin E, several other examples, natural and synthetic, have been reported. Given the dire need for new antibiotics that are structurally and mechanistically distinct from anything that has come before, MBAMPs potentially offer new hope in the fight against antimicrobial resistance. This review covers recent advances in the discovery, characterization, synthesis and derivatization, and mechanistic understanding of MBAMPs.