Article

Cloning and Characterization of an Environmental DNA-Derived Gene Cluster That Encodes the Biosynthesis of the Antitumor Substance BE-54017

Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
Journal of the American Chemical Society (Impact Factor: 11.44). 05/2011; 133(26):9996-9. DOI: 10.1021/ja2022653
Source: PubMed

ABSTRACT 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 gene clusters can be recovered and studied. The screening of an archived soil DNA library using primers designed to target oxytryptophan dimerization genes allowed us to identify and functionally characterize the first indolotryptoline biosynthetic gene cluster. The recovery and heterologous expression of an environmental DNA-derived gene cluster encoding the biosynthesis of the antitumor substance BE-54017 is reported here. Transposon mutagenesis identified two monooxygenases, AbeX1 and AbeX2, as being responsible for the transformation of an indolocarbazole precursor into the indolotryptoline core of BE-54017.

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