Genome mining for drug discovery: Activation of silent biosynthetic gene clusters

acronym: GenoDrug

Results of GenoDrug
(click here)

Project coordinator
- Prof. Lutz Heide - Eberhard Karls Universität Tübingen - Germany
  Prof. Wolfgang Wohlleben - Eberhard Karls Universität Tübingen -
Project leaders
- Dr. Carmen Méndez - Universidad de Oviedo - Spain
- Prof. Jolanta Zakrzewska-Czerwinska - University of Wroc³aw - Poland
- Dr. E. Takano - University of Groningen - The Netherlands
- Francisco Moris - EntreChem SL - Spain
- Maria Holmbäck/Kristiina Ylihonko - Galilaeus Oy - Finland

The GenoDrug proposal aims at the development of a new technology for drug discovery,  i.e. the activation of previously silent biosynthetic gene clusters of microbial genomes. Microbial natural products have an outstanding track record as drugs and drug leads since more than sixty years. However, conventional screening programs increasingly result in the re-discovery of already known compounds. Sequencing of many microbial genomes, especially from actinomycetes, has now revealed that the genome of each strain contains gene clusters for the formation of 10-30 bioactive compounds ("secondary metabolites"). This implies that for any actinomycete strain most of its potential as producer of bioactive compounds is yet undiscovered. An economy which can harness this potential is likely to take an international lead in the development of new antibiotics, anticancer drugs and other pharmaceuticals in future.
The bottleneck in the economical exploitation of this strategy is the development of technologies which allow the utilization of DNA sequence data of secondary metabolic gene clusters to generate the encoded compounds, in quantities sufficient for characterization, pharmacological testing and preclinical drug development. The GenoDrug proposal will develop such technologies and demonstrate their applicability in drug discovery by the identification of several novel bioactive compounds.