Design and heterologous expression of a novel dimeric LL37 variant in Pichia pastoris

Background The antimicrobial peptide LL37 is produced by white blood cells (mainly neutrophils) and various epithelial cells, and has the outstanding advantages of participating in immune regulation, causing chemotaxis of immune cells and promoting wound healing. However, the central domain of LL37 needs to be improved in terms of antimicrobial activity. Results In this study, the amino acid substitution method was used to improve the antimicrobial activity of the LL37 active center, and a dimeric design with a better selection index was selected. A flexible linker was selected and combined with the 6 x His-SUMO tag and LG was successfully expressed using Pichia pastoris as a host. Recombinant LG displayed strong antimicrobial activity by destroying the cell membrane of bacteria but had low hemolytic activity. In addition, compared with monomeric peptide FR, rLG had improved ability to tolerate salt ions. Conclusion This research provides new ideas for the production of modified AMPs in microbial systems and their application in industrial production.

Automated summary

This study improved the antimicrobial activity of LL37 by amino acid substitution and dimeric design, successfully expressing recombinant LG with strong antimicrobial activity and low hemolytic activity, as well as improved tolerance to salt ions compared to monomeric peptide FR.