Discovery, synthesis and characterisation of Streptomyces-derived novel anti-MRSA protein

Whole genome sequencing of a novel Streptomyces pluripotens MUSC 135T was performed. A core biosynthetic gene was predicted to produce linear azole-containing peptides (LAPs) using bioinformatics tools, such as antiSMASH, PRISM, GECCO, and SeMPI. Protein 135 was expressed from the selected core biosynthetic gene and showed significant antibacterial activity against Methicillin-Resistant Staphylococcus aureus (MRSA). It outperformed the vancomycin against MRSA under the sub-MIC concentrations. Molecular docking studies predicted that Protein 135 exerts its antibacterial effect by binding to the bacterial 16S rRNA A-site, thereby disrupting protein synthesis. This research provides valuable insights for developing new antibiotics.