title: Global biogeographic sampling of bacterial secondary metabolism.
abstract: Recent bacterial (meta)genome sequencing efforts suggest the existence of an enormous untapped reservoir of natural-product-encoding biosynthetic gene clusters in the environment. Here we use the pyro-sequencing of PCR amplicons derived from both nonribosomal peptide adenylation domains and polyketide ketosynthase domains to compare biosynthetic diversity in soil microbiomes from around the globe. We see large differences in domain populations from all except the most proximal and biome-similar samples, suggesting that most microbiomes will encode largely distinct collections of bacterial secondary metabolites. Our data indicate a correlation between two factors, geographic distance and biome-type, and the biosynthetic diversity found in soil environments. By assigning reads to known gene clusters we identify hotspots of biomedically relevant biosynthetic diversity. These observations not only provide new insights into the natural world, they also provide a road map for guiding future natural products discovery efforts.
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, Rockefeller University, New York, United States.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Charlop-Powers
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, Rockefeller University, New York, United States.
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Owen
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, Rockefeller University, New York, United States.
authors.forename: Boojala Vijay B
authors.initials: BV
authors.lastname: Reddy
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, Rockefeller University, New York, United States.
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Ternei
authors.affiliation: Laboratório de Produtos Naturais, Curso de Farmácia, Universidade Federal do Rio de Janeiro-Campus Macaé, Rio de Janeiro, Brazil.
authors.forename: Denise O
authors.initials: DO
authors.lastname: Guimarães
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Ulysses A
authors.initials: UA
authors.lastname: de Frias
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Monica T
authors.initials: MT
authors.lastname: Pupo
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R Mandela School of Medicine, Durban, South Africa.
authors.forename: Prudy
authors.initials: P
authors.lastname: Seepe
authors.affiliation: College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China.
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, Rockefeller University, New York, United States.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Brady
mesh_terms: D001419:Bacteria / Q000201:enzymology / Q000378:metabolism*; D001483:Base Sequence; D044822:Biodiversity; D001688:Biological Products / Q000378:metabolism; D058974:Phylogeography; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D064210:Secondary Metabolism
chemical_list: D001688:Biological Products; D048630:Polyketide Synthases
keywords: biogeography; biosynthesis; evolutionary biology; genomics; infectious disease; metagenomics; microbiology; natural products; none