Identification of Natural Product Biosynthetic Gene Clusters from Bacterial Genomic Data

The frequent re-isolation of known compounds is one of the main challenges of traditional screening methods for natural products drug discovery. The ability to connect natural products to the genes that encode them and vice versa has the potential to revolutionize discovery efforts. Increasingly sophisticated bioinformatic tools are being developed that are able to not only identify biosynthetic genes in sequenced genomes but can also predict the product class or structure in silico. This information can then guide targeted discovery of new compounds. In this chapter, we will describe how to prioritize bacterial strains for genome sequencing and how biosynthetic gene clusters can be identified in bacterial genomes. We will also give a short introduction on how comparative genomics can help to identify different congeners of a specific class of natural products of interest and what the limitations of structure prediction are. We will not attempt to be exhaustive but will rather provide examples that the reader can actively follow.