Background

The natural product etnangien, originally isolated from the myxobacterium Sorangium cellulosum, represents a new structural type of a particularly efficient RNA polymerase inhibitor. It is effective against a broad panel of Gram-positive bacteria, including rifampicin resistant strains. Etnangien also retains activity against retroviral DNA polymerase and shows only low cytotoxicity against mammalian cell cultures, which add to the attractiveness for further development. Preclinical advancement is severely hampered by the notorious instability of etnangien, which is associated with chemical structural elements.

Invention

Inventors of Saarland University were able to identify the genecluster encoding the biosynthesis genes of Etnangien in Sorangium cellulosum. The availability of the biosynthesis genes of etnangien enables genetic manipulations in the natural host to produce modified etnangien. These can be used for further derivatisations, resulting in etnangien with improved stability compared to the natural compound. The invention also offers the possibility to heterologously produce etnangien in a production strain of different genera to finally optimise the fermentation conditions and the yields. Further development of etnangien as an antibacterial pharmaceutical is now realizable.

Advantages

• Production of structurally improved etnangien by side-directed mutagenesis
• Optimised fermentation by heterologous production in a non-natural host