title: 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.
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (USA).
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Chang
authors.forename: Sean F
authors.initials: SF
authors.lastname: Brady
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D015723:Gene Library; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D008301:Maleimides / Q000737:chemistry / Q000378:metabolism*; D056186:Metagenomics; D005810:Multigene Family; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012988:Soil Microbiology
chemical_list: D001426:Bacterial Proteins; D007211:Indoles; D008301:Maleimides; D011994:Recombinant Proteins; D004247:DNA; C088060:bisindolylmaleimide
keywords: Rieske dioxygenase; biosynthesis; bisindolylmaleimides; metagenomics; natural products