Engineering glycopeptide antibiotic biosynthesis to produce novel antibiotics

01.01.2025 bis 31.12.2026

Glycopeptide antibiotics (GPAs), such as vancomycin, are key therapeutics in the fight against Gram-positive pathogens. However, the emergence of vancomycin resistance highlights the urgent need for innovative strategies against antibiotic resistance. GPAs exhibit remarkable structural diversity and biosynthetic complexity, involving non-ribosomal peptide synthetases (NRPSs), oxidative cascades and post-synthetic modifications. However, their exclusive in vivo production requires a thorough understanding of their biosynthesis to redesign and develop novel variants capable of combating resistant bacterial strains.
Central to GPA biosynthesis are the NRPS, which act as a mega-enzyme assembly line, orchestrating the incorporation of amino acids into the growing peptide chain. The ability of the NRPSs to integrate diverse amino acids beyond the ribosomal code underscores the structural diversity of the peptides they produce, with over 300 different monomers identified to date.
Project description with WoM – PPP – P33 – 02/2024– 4.0 Page 2 of 10