ENHANCE

Elucidation of the biosynthesis of the hydrazine containing compound negamycin

01/01/2024 to 31/12/2026

Negamycin is a metabolite isolated from cultures of Kitasatospora purpeofusca. It has antibacterial activity especially against bacteria from the ESKAPE list (Klebsiella pneumonia, Enterobacter sp. and Pseudomonas aeruginosa), for which new antibiotics are urgently needed. It also exhibits stop-codon readthrough activity, and could therefore be used for the treatment of genetic diseases caused by mutations leading to in-frame stop codons (e.g. some forms of the Duchenne muscular dystrophy or cystic fibrosis). In this project, we aim to (I) precisely define and characterize the negamycin biosynthetic gene cluster (BGC), (II) elucidate the biosynthetic pathway of negamycin, (III) elucidate the self-resistance mechanism of the negamycin producer strain (IV) optimize the production of negamycin in quantities sufficient for biological studies (V) further investigate the readthrough activities of negamycin and its natural analogues toward nonsense mutations.