Since the discovery of penicillin in 1928, bacteria have been unsurpassed as a source of new chemistry to fight emerging disease and infections. In the last 15 years, has genome sequencing has revealed the phenomenal chemical potential of bacteria. This has allowed the DNA blueprint (genes) for all microbial metabolites, including potentially the next blockbuster drug, to be observed. Surprisingly, even well studied bacteria were found to maintain the genetic potential to produce many more metabolites than discovered thus far. For example, the genome of Streptomyces avermitilis encoded for up to 10 times the number of secondary metabolites than were previously known. Furthermore, it has been estimated that 90% of secondary metabolite genes predicted from genome sequencing are cryptic (no known product) under standard fermentation conditions. Advancing technology and decreasing cost affords the era of comparative genomics. This enables genomic diversity to be described, across thousands of strains. Currently there is no automated way to connect secondary metabolite genes with their metabolite products. Here we propose a comparative multi-omics platform to integrate genomics and metabolomics.
As a case study, we will focus on the biosynthetic and chemical potential of ancient Antarctic and Arctic bacteria using this novel platform approach for accelerated drug discovery. Our proposed activities are timely, as this bacterial resource of understudied chemistry will diminish under future climate predications.