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Expanding Small-Molecule Functional Metagenomics through Parallel Screening of Broad-Host-Range Cosmid Environmental DNA Libraries in Diverse Proteobacteria
ABSTRACT The small-molecule biosynthetic diversity encoded within the genomes of uncultured bacteria is an attractive target for the discovery of natural products using functional metagenomics.Expand
Natural products from environmental DNA hosted in Ralstonia metallidurans.
Metagenomic studies designed to access new small molecules from the heterologous expression of environmental DNA have focused on the use of two model systems, Escherichia coli and Streptomyces spp.,Expand
Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases
The gut microbiota modulate host biology in numerous ways, but little is known about the molecular mediators of these interactions. Previously, we found a widely distributed family of nonribosomalExpand
Cloning and characterization of an environmental DNA-derived gene cluster that encodes the biosynthesis of the antitumor substance BE-54017.
Soil is predicted to contain thousands of unique bacterial species per gram. Soil DNA libraries represent large reservoirs of biosynthetic diversity from which diverse secondary metabolite geneExpand
A Pressure Test to Make 10 Molecules in 90 Days: External Evaluation of Methods to Engineer Biology.
Centralized facilities for genetic engineering, or "biofoundries", offer the potential to design organisms to address emerging needs in medicine, agriculture, industry, and defense. The field hasExpand
Targeted metagenomics: finding rare tryptophan dimer natural products in the environment.
Natural product discovery from environmental genomes (metagenomics) has largely been limited to the screening of existing environmental DNA (eDNA) libraries. Here, we have coupled aExpand
Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters
Significance A rapidly growing number of cryptic natural product biosynthetic gene clusters have been identified in bacterial DNA sequencing datasets. The metabolites encoded by most of these geneExpand
Mutations in the Proteolipid Subunits of the Vacuolar H+-ATPase Provide Resistance to Indolotryptoline Natural Products
Indolotryptoline natural products represent a small family of structurally unique chromopyrrolic acid-derived antiproliferative agents. Like many prospective anticancer agents before them, theExpand
Discovery of indolotryptoline antiproliferative agents by homology-guided metagenomic screening
Natural product discovery by random screening of broth extracts derived from cultured bacteria often suffers from high rates of redundant isolation, making it ever more challenging to identify novelExpand
Discovery and synthetic refactoring of tryptophan dimer gene clusters from the environment.
Here we investigate bacterial tryptophan dimer (TD) biosynthesis by probing environmental DNA (eDNA) libraries for chromopyrrolic acid (CPA) synthase genes. Functional and bioinformatics analyses ofExpand