RRC ID 4998
著者 Kim SY, Park JS, Chae CS, Hyun CG, Choi BW, Shin J, Oh KB.
タイトル Genetic organization of the biosynthetic gene cluster for the indolocarbazole K-252a in Nonomuraea longicatena JCM 11136.
ジャーナル Appl Microbiol Biotechnol
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.
巻・号 75(5)
ページ 1119-26
公開日 2007-7-1
DOI 10.1007/s00253-007-0924-x
PMID 17396254
MeSH Actinomycetales / enzymology* Actinomycetales / genetics* Carbazoles / metabolism* Cloning, Molecular Genetic Engineering Indole Alkaloids / metabolism* Multigene Family* Streptomyces / enzymology Streptomyces / genetics
IF 3.53
引用数 22
WOS 分野 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
リソース情報
一般微生物 JCM11136