Large-scale Discovery of Novel Antibiotics

The goal of the project is the development of methods for rapid, high-throughput discovery of novel antibiotics to counter the scourge of anti-microbial
resistant pathogens. About 75% of the currently used antibiotics are derived from microbial natural products, while nearly 60% of anti-cancer drugs find a similar origin. Ironically, at a time of great need, many pharmaceutical companies have reduced their natural product screening programs. This is not because new metabolites cannot be found, but rather because current screening methods are producing dramatically declining numbers of promising new candidates. To face this dilemma, new methods for high-throughput screening and identification of useful microbial products are needed. Fortunately, recent innovations in genome-mining approaches provide us the means to screen microbes for novel therapeutic agents on an unprecedented scale. Metcalf’s team has sequenced 500 cultivable Actinomycete genomes, and there are plans to sequence close to 10,000 genomes, with the goal of identifying the full complement of bioactive natural products (secondary metabolites) produced by these strains. By scaling natural product screening to a
new level this project can greatly accelerate the development of next generation medicines. Our goal, in collaboration with the Metcalf laboratory, is to use KnowEnG to link specific genes and gene families with specific secondary metabolites and to predict which Actinomycetes strains are likely to
produce novel compounds with potential antibiotic activity.