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Culture-independent discovery of natural products from soil metagenomes

  • Natural Products
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Bacterial natural products have proven to be invaluable starting points in the development of many currently used therapeutic agents. Unfortunately, traditional culture-based methods for natural product discovery have been deemphasized by pharmaceutical companies due in large part to high rediscovery rates. Culture-independent, or “metagenomic,” methods, which rely on the heterologous expression of DNA extracted directly from environmental samples (eDNA), have the potential to provide access to metabolites encoded by a large fraction of the earth’s microbial biosynthetic diversity. As soil is both ubiquitous and rich in bacterial diversity, it is an appealing starting point for culture-independent natural product discovery efforts. This review provides an overview of the history of soil metagenome-driven natural product discovery studies and elaborates on the recent development of new tools for sequence-based, high-throughput profiling of environmental samples used in discovering novel natural product biosynthetic gene clusters. We conclude with several examples of these new tools being employed to facilitate the recovery of novel secondary metabolite encoding gene clusters from soil metagenomes and the subsequent heterologous expression of these clusters to produce bioactive small molecules.

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    Authors and Affiliations

    1. Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

      Micah Katz, Bradley M. Hover & Sean F. Brady

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    1. Micah Katz
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    2. Bradley M. Hover
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    3. Sean F. Brady
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    Correspondence to Sean F. Brady.

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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.

    M. Katz and B. M. Hover contributed equally to the writing of this review.

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    Katz, M., Hover, B.M. & Brady, S.F. Culture-independent discovery of natural products from soil metagenomes. J Ind Microbiol Biotechnol 43, 129–141 (2016). https://doi.org/10.1007/s10295-015-1706-6

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