title: Culture-independent discovery of natural products from soil metagenomes.
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.
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
authors.forename: Micah
authors.initials: M
authors.lastname: Katz
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Hover
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA. sbrady@rockefeller.edu.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Brady
mesh_terms: D001419:Bacteria / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D001688:Biological Products / Q000302:isolation & purification* / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D055808:Drug Discovery; D006801:Humans; D054892:Metagenome; D056186:Metagenomics; D064210:Secondary Metabolism / Q000235:genetics; D012987:Soil / Q000737:chemistry; D012988:Soil Microbiology
chemical_list: D001688:Biological Products; D012987:Soil; D004247:DNA
keywords: Culture-independent; Drug discovery; Metagenomics; Natural products