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

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.

SUBMITTER: Chang FY

PROVIDER: S-EPMC4028703 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Chang Fang-Yuan FY Brady Sean F SF

Chembiochem : a European journal of chemical biology 20140319 6

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 (C ...[more]

PMID: 24648189

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