A Biotechnological Platform for Gram-Scale Production of Mureidomycin A

Mureidomycin A is a uridyl peptide antibiotic with potent bioactivity against the Gram-negative pathogen Pseudomonas aeruginosa. Crucial bottlenecks impeding further drug development include low compound production in native producers and heterologous hosts, as well as the formation of numerous derivatives, which further reduces the yield of the target compound. By analyzing different production hosts and deleting single genes, a production platform for mureidomycin A was developed in this study. The production of several derivatives was reduced or abolished, facilitating compound isolation. While mureidomycin A was previously produced in trace amounts, the final strain yields ∼1.4 g/L, enabling future preclinical studies.