title: Genetic organization of the biosynthetic gene cluster for the indolocarbazole K-252a in Nonomuraea longicatena JCM 11136.
abstract: Indolocarbazole metabolite K-252a is a natural product that was previously reported as a potent protein kinase C inhibitor with in vitro and in vivo potency. From a biosynthetic viewpoint, this compound possesses structurally interesting features such as an unusual furanosyl sugar moiety, which are absent in the well-studied staurosporine and rebeccamycin. A cosmid library from genomic DNA of Nonomuraea longicatena JCM 11136 was constructed and screened for the presence of genes to be involved in the biosynthesis of indolocarbazole K-252a. Using as a probe an internal fragment of vioB, a Chromobacterium violaceum gene encoding a multifunctional enzyme that catalyzes tryptophan decarboxylation and condensation reaction in violacein biosynthesis, we isolated a DNA region that directed the biosynthesis of K-252a when introduced into the heterologous expression host Streptomyces albus. Sequence analysis of 45 kb revealed genes for indolocarbazole core formation, glycosylation, and sugar methylation, as well as a regulatory gene and two resistance/secretion genes. The cloned genes should help to elucidate the molecular basis for indolocarbazole biosynthesis and generate new indolocarbazole analogues by genetic engineering.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-921, South Korea.
authors.forename: Seung-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Jin-Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Choong-Sik
authors.initials: CS
authors.lastname: Chae
authors.forename: Chang-Gu
authors.initials: CG
authors.lastname: Hyun
authors.forename: Byoung Wook
authors.initials: BW
authors.lastname: Choi
authors.forename: Jongheon
authors.initials: J
authors.lastname: Shin
authors.forename: Ki-Bong
authors.initials: KB
authors.lastname: Oh
mesh_terms: D000192:Actinomycetales / Q000201:enzymology* / Q000235:genetics*; D002227:Carbazoles / Q000378:metabolism*; D003001:Cloning, Molecular; D005818:Genetic Engineering; D026121:Indole Alkaloids / Q000378:metabolism*; D005810:Multigene Family; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics
chemical_list: D002227:Carbazoles; D026121:Indole Alkaloids; C049985:staurosporine aglycone