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Nat Commun. 2015 Sep 28;6:8421. doi: 10.1038/ncomms9421.

An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.

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Department of Biochemistry &Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research; McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Department of Chemistry &Chemical Biology, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
The David R. Cheriton School of Computer Science, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Department of Chemistry; Queens University, Kingston, Ontario, Canada K7L 3N6.


Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC-MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products.

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