High-Throughput Discovery of New Natural Products and Their Biosynthetic Gene Clusters Using a Metabologenomics Approach

摘要

Natural product discovery is undergoing rapid reformation due to the advances in genomics and analytical chemistry. Novel genome mining methods promise to unleash a stream of new molecules from the historical source of many of the most potent treatments for cancer and infectious diseases. Inspired by advances in acquisition and analysis of metabolomics LC-MS data, we developed an approach called metabologenomics to simultaneously discover natural products and their biosynthetic gene clusters. Metabologenomics determines the relationships between clusters of biosynthetic genes, and the small molecules that they produce by identifying their co-occurrence across multiple organisms. We identified a bioactive, halogenated peptide called tambromycin in 9 species of Streptomyces, as well as the biosynthetic gene cluster that produces it.