Antimicrobial peptides (AMPs) have broad-spectrum antibacterial properties and safety as food preservatives, whereas the stability and antibacterial activity require improvement. Here, the "head-to-tail" cyclization of linear AMP GKE was catalyzed by butelase 1, which resulted in an improved pronouncedly antibacterial effect. Cell morphology and propidium iodide uptake revealed that the increased membrane permeability was one of the bacteriostatic mechanisms of GKE and could be enhanced after cyclization. As cyclic GKE (cGKE) exhibited more stability than the linear counterpart under the microorganism culture environment, the increase in effective bacteriostatic concentration should be a reason for the superior antibacterial effect. Moreover, cGKE exhibited the ordered secondary structure, while GKE possessed a similar structure only in sodium dodecyl sulfate micelles. The structure was also beneficial to improve the antibacterial activity caused by the increased affinity of cGKE to the membranes. Overall, butelase 1-mediated cyclization is a promising strategy for enhancing the antibacterial activity of linear AMPs.
Keywords: antibacterial activity; antibacterial mechanism; antimicrobial peptides; butelase 1-mediated cyclization; structural stability.