Natural products have been the most abundant source of therapeutic leads over the past 100 years. Significant compounds have been discovered from myriad source materials, making continued exploration of biological sources an important goal. A major bottleneck in the drug development process is the isolation and identification of novel compounds from natural sources. Current methods involve the iterative process of compound isolation guided by bioactivity assays followed structural characterization. This approach is slow, often misses low-abundant molecules and the probability of identifying a previously-known compound after the input of significant effort is high. We are combining mass spectrometry and bioinformatics to expedite the identification of low abundant compounds whose production has been predicted at the genome level, but have not been experimentally identified. We are applying this strategy to the discovery of compounds from Streptomyces sp., the highest antibiotic-producing genus in the world, whose secondary metabolome remains incompletely explored.

Development of a mass spectrometry-based approach for natural products discovery

245th National Meeting (2013)

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