1 research outputs found
Natural Product Discovery through Improved Functional Metagenomics in <i>Streptomyces</i>
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 <i>Streptomyces</i> 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 <i>Streptomyces</i> host. An initial screen of a 1.5 million-membered metagenomic library
constructed in <i>Streptomyces albus</i>, the species that
exhibited the highest propensity for heterologous expression of gene
clusters, led to the identification of the novel natural product metatricycloene
(<b>1</b>). 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