Characterization of an Environmental DNA‐Derived Gene Cluster that Encodes the Bisindolylmaleimide Methylarcyriarubin | Zendy

Chang FangYuan | Zendy; Brady Sean F. | Zendy

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Characterization of an Environmental DNA‐Derived Gene Cluster that Encodes the Bisindolylmaleimide Methylarcyriarubin

Author(s) -

Chang FangYuan,

Brady Sean F.

Publication year - 2014

Publication title -

chembiochem

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.05

H-Index - 126

eISSN - 1439-7633

pISSN - 1439-4227

DOI - 10.1002/cbic.201300756

Subject(s) - gene cluster , bisindolylmaleimide , gene , heterologous expression , biology , dna , biochemistry , decarboxylation , chemistry , genetics , kinase , protein kinase c , recombinant dna , catalysis

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.

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