Informatics-driven drug discovery from microbial metabolites

Samenvatting

Pharmaceutical research is under immense pressure to find new ways to battle emerging multidrug-resistant bacteria. Many of today?s antibiotics have been developed successfully from bacterial and fungal metabolites, although at too low speed and too high costs.

Such metabolites are genomically encoded by compact units: biosynthetic gene clusters. I have recently identified thousands of such gene clusters in the DNA of microorganisms all across the tree of life, which encode a plethora of unknown molecules. However, experimental characterization is a laborious task, and only a subset of molecules are medically useful.

To efficiently identify this subset, it will be vital to optimally sample the existing diversity at different levels.

I will use informatics to integrate data from biochemistry (molecules), enzymology (enzymes), genomics (gene clusters) and ecology (environment) to this purpose. While the structural diversity of molecules can be predicted based on the combinations of enzymes encoded in their gene clusters, their functional diversity can be mined by selecting molecules from diverse environments and ecological niches.

Based on this knowledge, I will prioritize high-potential gene clusters for implementation in dedicated synthetic biology approaches. This will pave the path to unleash the full chemical potential found in nature to accelerate drug development.

Keywords: antibiotics, secondary metabolism, standardization, ecology & evolution, synthetic biology

Producten

Wetenschappelijk artikel

Kenmerken

Projectnummer

825.13.001

Hoofdaanvrager

Dr. M.H. Medema

Verbonden aan

Wageningen Universiteit & Researchcentrum, Plantenwetenschappen, Bioinformatics

Uitvoerders

Dr. M.H. Medema

Looptijd

01/08/2013 tot 17/09/2015