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Informatic search strategies to discover analogues and variants of natural product archetypes

  • Biotechnology Methods
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Natural products are a crucial source of antimicrobial agents, but reliance on low-resolution bioactivity-guided approaches has led to diminishing interest in discovery programmes. Here, we demonstrate that two in-house automated informatic platforms can be used to target classes of biologically active natural products, specifically, peptaibols. We demonstrate that mass spectrometry-based informatic approaches can be used to detect natural products with high sensitivity, identifying desired agents present in complex microbial extracts. Using our specialised software packages, we could elaborate specific branches of chemical space, uncovering new variants of trichopolyn and demonstrating a way forward in mining natural products as a valuable source of potential pharmaceutical agents.

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Acknowledgments

This work was funded through a Natural Sciences and Engineering Research Council (NSERC) of Canada Discovery grant (RGPIN 371576-2014) (NAM) and a Joint Programme Initiative on Antimicrobial Resistance funded through the Canadian Institutes of Health Research (NAM). CWJ is funded through a CIHR Doctoral Research Award. NAM is supported by the Canada Research Chairs Program.

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Correspondence to Nathan A. Magarvey.

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Special Issue: Natural Product Discovery and Development in the Genomic Era. Dedicated to Professor Satoshi Ōmura for his numerous contributions to the field of natural products.

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Johnston, C.W., Connaty, A.D., Skinnider, M.A. et al. Informatic search strategies to discover analogues and variants of natural product archetypes. J Ind Microbiol Biotechnol 43, 293–298 (2016). https://doi.org/10.1007/s10295-015-1675-9

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