Sequencing Call

DZIF Sequencing Measures - Aufstockung zu Förderkennzeichen 8020809825

01.07.2021 bis 31.12.2021

Pseudomonas aeruginosa is a fearsome hospital germ and can cause severe chronic respiratory infections. In particular due to the increasing resistance to reserve antibiotics such as carbapenem, the World Health Organization (WHO) has given the germ on its current priority list the priority "critical" and has asked governments, academia and research-based pharmaceutical companies to develop new drugs against this pathogen.
Mureidomycins belong, together with the pacidamycins, the napsamycins and the sansamycins, to the group of uridyl peptide antibiotics that guarantee both, a potent antipseudomonal activity (MIC 0.1-3 µg/mg) and low toxicity (ED50 70 mg/kg in a mouse model). The antibacterial activity is mediated through the inhibition of the enzyme MraY, which in turn leads to the inhibition of the cell wall biosynthesis. Mureidomycin C is the most potent member of this compound family. Total syntheses are described, but are not economical for large-scale production. In the preceding DZIF funding period a biotechnological platform for the production of small scales was established by project TTU09.820_00. For this purpose, the pacidamycin gene cluster was re-programmed in order to produce mureidomycin C heterologously. However, the expression profile and the interaction of the modified gene cluster with primary metabolism of the host was not studied so far. In order to predict possible bottlenecks of mureidomycin C production, a comparative and quantitative RNA sequencing of different strains containing different stages of the modified gene cluster would detect production limitations on the transcriptional level.