Leiden: Screening tool to identify cryptic antibiotics

Submitted by Leiden University Research & Innovation Services

Licensing opportunity

The study of genome sequences of actinomycetes has unveiled a surprisingly large number of cryptic antibiotic biosynthesis clusters. Cryptic antiobic clusters are under normal circumstances dormant, with undetectable expression levels. Inducing these clusters and selecting the species that express interesting products can lead to a whole range of products with industrial or pharmaceutical application.

Researchers of the Universities of Leiden, Liège (Belgium) and Erlangen (Germany) have discovered that the DasR protein is a regulatory master switch that is involved in multiple metabolic processes in micro-organisms and a global inhibitor of known and cryptic biosynthesis clusters for natural products. This invention relates to the manipulation of the activity of DasR, a.o. by the use of a very potent inducer that relieves DasR control. This will result in the enhanced expression of cryptic antibiotics. The ability to control gene expression by external DasR modulators enables high-throughput screening to allow uncovering previously undetected antibiotics and other natural products (anticancer, antifungals). Once identified, the patented technology also provides the tools to upregulate the production of these products in actinomycetes.

The proof of concept of the technology has been delivered. The Universities of Leiden, Liège and Erlangen are looking for license and collaboration opportunities.

Key Benefits:

• Allows production of previously undetected natural products (antibiotics, anti-cancer) by actinomycetes by the addition of a non-toxic compound

• Method is simple and fast

• Method allows high throughput screening and selection of strains

Applications:

Production of antibiotics and other natural products produced by actinomycetes