Tetrapeptide from microbial coculture exhibiting a unique algicidal mechanism against Alexandrium fundyense

Alexandrium fundyense is a thecate dinoflagellate species associated with harmful algal blooms that impact fisheries, marine ecosystems, and human health. Bioactive peptides from marine organisms are considered promising algicidal agents. However, studies on peptides effective against thecate dinoflagellates remain scarce, and their mechanisms of action are largely unexplored. This study investigates the algicidal mechanism of a tetrapeptide obtained from a microbial coculture of food waste, previously identified for its activity against A. fundyense. Unlike conventional algicidal peptides that typically disrupt cell membranes through hydrophobic interactions, this tetrapeptide induced algal cell death via a unique mechanism involving intracellular reactive oxygen species production, organelle breakdown (chloroplasts and mitochondria), and reduced esterase activity, without membrane disruption. Fluorescence microscopy confirmed peptide penetration and intracellular activity, further highlighting its distinct mechanism. Additionally, the tetrapeptide exhibited low toxicity toward non-target algae, suggesting environmental safety. This study expands understanding of algicidal mechanisms against thecate dinoflagellates by providing evidence for a non-membrane-disruptive mode of action, thereby supporting the development of bioactive peptides as sustainable tools for harmful algal bloom management. These findings suggest that fishery waste-derived peptides can offer environmentally friendly solutions with unique modes of action for mitigating harmful algal blooms.