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

Chad W. Johnston, Michael A. Skinnider, Morgan A. Wyatt, Xiang Li, Michael R.M. Ranieri, Lian Yang, David L. Zechel, Bin Ma, Nathan A. Magarvey

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number8421
JournalNature communications
Volume6
DOIs
StatePublished - Sep 28 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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