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

Author

Listed:
  • Chad W. Johnston

    (M. G. DeGroote Institute for Infectious Disease Research
    McMaster University
    M. G. DeGroote Institute for Infectious Disease Research, McMaster University)

  • Michael A. Skinnider

    (M. G. DeGroote Institute for Infectious Disease Research
    McMaster University
    M. G. DeGroote Institute for Infectious Disease Research, McMaster University)

  • Morgan A. Wyatt

    (M. G. DeGroote Institute for Infectious Disease Research
    McMaster University
    M. G. DeGroote Institute for Infectious Disease Research, McMaster University)

  • Xiang Li

    (M. G. DeGroote Institute for Infectious Disease Research
    McMaster University
    M. G. DeGroote Institute for Infectious Disease Research, McMaster University)

  • Michael R. M. Ranieri

    (M. G. DeGroote Institute for Infectious Disease Research
    McMaster University
    M. G. DeGroote Institute for Infectious Disease Research, McMaster University)

  • Lian Yang

    (The David R. Cheriton School of Computer Science, University of Waterloo)

  • David L. Zechel

    (Department of Chemistry; Queens University
    Queens University)

  • Bin Ma

    (The David R. Cheriton School of Computer Science, University of Waterloo)

  • Nathan A. Magarvey

    (M. G. DeGroote Institute for Infectious Disease Research
    McMaster University
    M. G. DeGroote Institute for Infectious Disease Research, McMaster University)

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.

Suggested Citation

  • 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, 2015. "An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9421
    DOI: 10.1038/ncomms9421
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    Cited by:

    1. Donghui Yan & Muqing Zhou & Abhinav Adduri & Yihao Zhuang & Mustafa Guler & Sitong Liu & Hyonyoung Shin & Torin Kovach & Gloria Oh & Xiao Liu & Yuting Deng & Xiaofeng Wang & Liu Cao & David H. Sherman, 2024. "Discovering type I cis-AT polyketides through computational mass spectrometry and genome mining with Seq2PKS," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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