Optimization of the antimicrobial peptide Bac7 by deep mutational scanning

Autor: Philipp, Koch, Steven, Schmitt, Alexander, Heynisch, Anja, Gumpinger, Irene, Wüthrich, Marina, Gysin, Dimitri, Shcherbakov, Sven N, Hobbie, Sven, Panke, Martin, Held
Rok vydání: 2021
Předmět:
Zdroj: BMC biology. 20(1)
ISSN: 1741-7007
Popis: Intracellularly active antimicrobial peptides are promising candidates for the development of antibiotics for human applications. However, drug development using peptides is challenging as, owing to their large size, an enormous sequence space is spanned. We built a high-throughput platform that incorporates rapid investigation of the sequence-activity relationship of peptides and enables rational optimization of their antimicrobial activity. The platform is based on deep mutational scanning of DNA-encoded peptides and employs highly parallelized bacterial self-screening coupled to next-generation sequencing as a readout for their antimicrobial activity. As a target, we used Bac7Using the platform, we simultaneously determined the antimicrobial activity of600,000 Bac7We demonstrated that the presented platform can be used to establish the sequence-activity relationship of antimicrobial peptides, and showed its usefulness for hit-to-lead identification and optimization of antimicrobial drug candidates.
Databáze: OpenAIRE