Amyloid β-peptide multimer expressed in green algae efficiently inhibits bacteria growth by disrupting cell membrane...

Amyloid β-peptide, traditionally associated with Alzheimer's disease pathology, has recently been identified as a potential antimicrobial peptide (AMP) with broad-spectrum antibacterial activity. In this study, we utilized the green alga Chlamydomonas reinhardtii to express a multimeric form of amyloid β-peptide (3×amyloid β-peptide-HA-6×His). Following continuous passage over a period of five months, the expression of 3×amyloid β-peptide-HA-6×His was stabilized, resulting in a total soluble protein yield of 0.275% of the dry algal biomass. The peptide was shown to disrupt bacterial cell membranes, inhibiting the growth of both Gram-positive and Gram-negative bacteria. The antimicrobial peptide was stable across a range of temperatures, pH conditions, and proteases, and exhibited minimal hemolytic and cytotoxic effects on mammalian cells. Our findings suggest that amyloid β-peptide, previously regarded solely as a neurotoxic agent, may have significant potential as a therapeutic antimicrobial agent. The efficient production of this peptide in C. reinhardtii opens new possibilities for using algae as a biofactory for the large-scale production of bioactive antimicrobial peptides.