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 |