title: Biosynthetic gene cluster for the cladoniamides, bis-indoles with a rearranged scaffold.
abstract: The cladoniamides are bis-indole alkaloids isolated from Streptomyces uncialis, a lichen-associated actinomycete strain. The cladoniamides have an unusual, indenotryptoline structure rarely observed among bis-indole alkaloids. I report here the isolation, sequencing, and annotation of the cladoniamide biosynthetic gene cluster and compare it to the recently published gene cluster for BE-54017, a closely related indenotryptoline natural product. The cladoniamide gene cluster differs from the BE-54017 gene cluster in gene organization and in the absence of one N-methyltransferase gene but otherwise contains close homologs to all genes in the BE-54017 cluster. Both gene clusters encode enzymes needed for the construction of an indolocarbazole core, as well as flavin-dependent enzymes putatively involved in generating the indenotryptoline scaffold from an indolocarbazole. These two bis-indolic gene clusters exemplify the diversity of biosynthetic routes that begin from the oxidative dimerization of two molecules of L-tryptophan, highlight enzymes for further study, and provide new opportunities for combinatorial engineering.
authors.affiliation: Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada. ksryan@chem.ubc.ca
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Ryan
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics*; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism; D002243:Carbolines / Q000378:metabolism; D005798:Genes, Bacterial / Q000235:genetics*; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics*
chemical_list: D000470:Alkaloids; D001426:Bacterial Proteins; D002227:Carbazoles; D002243:Carbolines; D007211:Indoles; C009804:tryptoline; C053339:rebeccamycin