Genome Mining

Discovering the Biosynthetic Potential of Bacteria

The ability to predict the biosynthetic potential of microorganisms from their genome sequences (“from genes to molecules”) and the ability to predict which genes should code for biosynthesis of a particular natural product (“from molecules to genes”) has the potential to revolutionize drug discovery and development efforts:

1) With the explosion of microbial genome sequences available, it has become clear that the biosynthetic potential of microorganisms is much higher than what you see through fermentation. A typical, natural product-producing bacterium will be known to make a few compounds, but ~30 may be predicted from its genome sequence. Why this discrepancy? Because most biosynthetic genes are silent or not well expressed under laboratory growth conditions. But knowing which genes are there (knowing what the potential is) gives you the chance to activate those genes and get the corresponding compounds.

2) Imagine you have a strain collection of 1,000s to 100,000s of strains. The ability to predict what types of natural products they can potentially make through genome mining, gives you the opportunity to select potentially “talented” strains to be included in the discovery pipeline.

3) Identifying the genes that encode the biosynthesis of a natural product of interest gives you the opportunity to engineer the biosynthesis for yield improvement or structure diversification.