Culture-independent discovery of natural products from soil metagenomes

doi:10.1007/s10295-015-1706-6

Review

. 2016 Mar;43(2-3):129-41.

doi: 10.1007/s10295-015-1706-6. Epub 2015 Nov 19.

Culture-independent discovery of natural products from soil metagenomes

Micah Katz¹, Bradley M Hover¹, Sean F Brady²

Affiliations

¹ Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
² Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA. sbrady@rockefeller.edu.

PMID: 26586404
DOI: 10.1007/s10295-015-1706-6

Review

Culture-independent discovery of natural products from soil metagenomes

Micah Katz et al. J Ind Microbiol Biotechnol. 2016 Mar.

. 2016 Mar;43(2-3):129-41.

doi: 10.1007/s10295-015-1706-6. Epub 2015 Nov 19.

Authors

Micah Katz¹, Bradley M Hover¹, Sean F Brady²

Affiliations

¹ Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
² Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA. sbrady@rockefeller.edu.

PMID: 26586404
DOI: 10.1007/s10295-015-1706-6

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.

Keywords: Culture-independent; Drug discovery; Metagenomics; Natural products.

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[1] Front Microbiol. 2015 Aug 28;6:890 - PubMed

[2] Front Microbiol. 2015 Aug 28;6:890 - PubMed

[3] Angew Chem Int Ed Engl. 2013 Oct 11;52(42):11063-7 - PubMed

[4] Angew Chem Int Ed Engl. 2013 Oct 11;52(42):11063-7 - PubMed

[5] Chembiochem. 2011 May 16;12(8):1230-6 - PubMed

[6] Chembiochem. 2011 May 16;12(8):1230-6 - PubMed

[7] Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2478-83 - PubMed

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[9] J Am Chem Soc. 2012 Dec 5;134(48):19552-5 - PubMed

[10] J Am Chem Soc. 2012 Dec 5;134(48):19552-5 - PubMed

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Culture-independent discovery of natural products from soil metagenomes

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Culture-independent discovery of natural products from soil metagenomes

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