Discovery of indolotryptoline antiproliferative agents by homology-guided metagenomic screening.

ABSTRACT: 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 novel biologically interesting natural products. Here we show that homology-based screening of soil metagenomes can be used to specifically target the discovery of new members of traditionally rare, biomedically relevant natural product families. Phylogenetic analysis of oxy-tryptophan dimerization gene homologs found within a large soil DNA library enabled the identification and recovery of a unique tryptophan dimerization biosynthetic gene cluster, which we have termed the bor cluster. When heterologously expressed in Streptomyces albus, this cluster produced an indolotryptoline antiproliferative a

SUBMITTER: Chang FY 

PROVIDER: S-EPMC3574908 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature