title: Natural Product Discovery through Improved Functional Metagenomics in Streptomyces.
abstract: Because the majority of environmental bacteria are not easily culturable, access to many bacterially encoded secondary metabolites will be dependent on the development of improved functional metagenomic screening methods. In this study, we examined a collection of diverse Streptomyces species for the best innate ability to heterologously express biosynthetic gene clusters. We then optimized methods for constructing high quality metagenomic cosmid libraries in the best Streptomyces host. An initial screen of a 1.5 million-membered metagenomic library constructed in Streptomyces albus, the species that exhibited the highest propensity for heterologous expression of gene clusters, led to the identification of the novel natural product metatricycloene (1). Metatricycloene is a tricyclic polyene encoded by a reductive, iterative polyketide-like gene cluster. Related gene clusters found in sequenced genomes appear to encode a largely unexplored collection of structurally diverse, polyene-based metabolites.
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, The Rockefeller University , 1230 York Avenue, New York, New York 10065, United States.
authors.forename: Hala A
authors.initials: HA
authors.lastname: Iqbal
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, The Rockefeller University , 1230 York Avenue, New York, New York 10065, United States.
authors.forename: Lila
authors.initials: L
authors.lastname: Low-Beinart
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, The Rockefeller University , 1230 York Avenue, New York, New York 10065, United States.
authors.forename: Joseph U
authors.initials: JU
authors.lastname: Obiajulu
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, The Rockefeller University , 1230 York Avenue, New York, New York 10065, United States.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Brady
mesh_terms: D001688:Biological Products / Q000378:metabolism*; D056186:Metagenomics; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001688:Biological Products