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Chembiochem. 2014 Apr 14;15(6):815-21. doi: 10.1002/cbic.201300756. Epub 2014 Mar 19.

Characterization of an environmental DNA-derived gene cluster that encodes the bisindolylmaleimide methylarcyriarubin.

Author information

1
Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (USA).

Abstract

Bisindolylmaleimides represent a naturally occurring class of metabolites that are of interest because of their protein kinase inhibition activity. From a metagenomic library constructed with soil DNA, we identified the four gene mar cluster, a bisindolylmaleimide gene cluster that encodes for methylarcyriarubin (1) production. Heterologous expression of the mar gene cluster in E. coli revealed that the Rieske dioxygenase MarC facilitates the oxidative decarboxylation of a chromopyrrolic acid (CPA) intermediate to yield the bisindolylmaleimide core. The characterization of the mar cluster defines a new role for CPA in the biosynthesis of structurally diverse bacterial tryptophan dimers.

KEYWORDS:

Rieske dioxygenase; biosynthesis; bisindolylmaleimides; metagenomics; natural products

PMID:
24648189
PMCID:
PMC4028703
DOI:
10.1002/cbic.201300756
[Indexed for MEDLINE]
Free PMC Article

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