Cloning and Expression of a Gene Encoding N-Glycosyltrasferase (ngt) from Saccharothrix aerocolonigenes ATCC39243.

Ohuchi, Takeshi; Ikeda‐Araki, Atsuko; Watanabe-Sakamoto, Ayako; Kojiri, Katsuhisa; Nagashima, Masao; Okanishi, Masanori; Suda, Hiroyuki

doi:10.7164/antibiotics.53.393

Cited by 31 publications

(21 citation statements)

References 14 publications

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“…2) Protein kinases and DNA topoisomerases are important in cell proliferation, so speciˆc inhibitors are promising candidates for antitumor drugs. In fact, UCN-01, 3) BMY-27557, 4) and J-109384 5) are indolocarbazoles now in clinical trials for cancer chemotherapy.…”

Section: Characterization Of the Biosynthetic Gene Cluster Ofmentioning

confidence: 98%

“…[8][9][10] Ohuchi et al reported cloning of the ngt gene encoding an Nglycosyltransferase from L. aerocolonigenes ATCC 39243. 5) The Ngt protein converted an indolocarbazole, J-104303, to its N-glucoside, indicating that ngt is responsible for N-glycosylation in rebeccamycin biosynthesis. Very recently, in aˆrst report about indolocarbazole antibiotics, Sanchez et al cloned the rebeccamycin biosynthetic genes, using an internal fragment of ngt as a probe.…”

Section: Characterization Of the Biosynthetic Gene Cluster Ofmentioning

confidence: 99%

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Characterization of the Biosynthetic Gene Cluster of Rebeccamycin fromLechevalieria aerocolonigenesATCC 39243

Onaka¹,

Taniguchi²,

Igarashi³

et al. 2003

Bioscience, Biotechnology, and Biochemistry

113

124

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The biosynthetic gene cluster for rebeccamycin, an indolocarbazole antibiotic, from Lechevalieria aerocolonigenes ATCC 39243 has 11 ORFs. To clarify their functions, mutants with rebG, rebD, rebC, rebP, rebM, rebR, rebH, rebT, or orfD2 disrupted were constructed, and the gene products were examined. rebP disruptants produced 11,11'-dichlorochromopyrrolic acid, found to be a biosynthetic intermediate by a bioconversion experiment. Other genes encoded N-glycosyltransferase (rebG), monooxygenase (rebC), methyltransferase (rebM), a transcriptional activator (rebR), and halogenase (rebH). rebT disruptants produced rebeccamycin as much as the wild strain, so rebT was probably not involved in rebeccamycin production. Biosynthetic genes of staurosporine, an another indolocarbazole antibiotic, were cloned from Streptomyces sp. TP-A0274. staO, staD, and staP were similar to rebO, rebD, and rebP, respectively, all of which are responsible for indolocarbazole biosynthesis, But a rebC homolog, encoding a putative enzyme oxidizing the C-7 site of pyrrole rings, was not found in the staurosporine biosynthetic gene cluster. These results suggest that indolocarbazole is constructed by oxidative decarboxylation of chromopyrrolic acid (11,11'-dichlorochromopyrrolic acid in rebeccamycin) generated from two molecules of tryptophan by coupling and that the oxidation state at the C-7 position depends on the additional enzyme(s) encoded by the biosynthetic genes.

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Section: Characterization Of the Biosynthetic Gene Cluster Ofmentioning

confidence: 98%

Section: Characterization Of the Biosynthetic Gene Cluster Ofmentioning

confidence: 99%

Characterization of the Biosynthetic Gene Cluster of Rebeccamycin fromLechevalieria aerocolonigenesATCC 39243

Onaka¹,

Taniguchi²,

Igarashi³

et al. 2003

Bioscience, Biotechnology, and Biochemistry

113

124

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“…Also, a gene (ngt) encoding an indolocarbazole N-glycosyltransferase had been cloned from the rebeccamycin producer Sac. aerocolonigenes ATCC39243 [19]. The ngt gene, when expressed in either Streptomyces lividans or Streptomyces mobaraensis, was responsible for the introduction of a D-glucose moiety into indolocarbazoles J-104303 and 6-N-methylarcyriaflavin C. These results suggested that ngt was probably involved in rebeccamycin biosynthesis, although no definite proof was reported at that time.…”

Section: Identification Of the Genes Responsible For Rebeccamycin Biomentioning

confidence: 71%

Engineering biosynthetic pathways to generate antitumor indolocarbazole derivatives

Sánchez

Méndez

Salas

2006

J IND MICROBIOL BIOTECHNOL

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The indolocarbazole family of natural products is a source of lead compounds with potential therapeutic applications in the treatment of cancer and neurodegenerative disorders. Rebeccamycin and staurosporine are two members of this family, which are produced by different actinomycete strains. Although both compounds display antitumor activity, their distinct structural features determine different modes of action: rebeccamycin targets DNA topoisomerase I, while staurosporine is a protein kinase inhibitor. Here we examine the biosyntheses of rebeccamycin and staurosporine while we summarize our recent work concerning (a) identification and characterization of genes involved in the biosynthesis of indolocarbazoles in actinomycetes, and (b) generation of novel indolocarbazole derivatives in microorganisms by combinatorial biosynthesis.

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“…On the other hand, cloning of the indolocarbazole biosynthetic genes was not performed until recently because the clue to gene cloning had not been revealed; therefore, the biosynthetic pathway of indolocarbazole compounds was also unknown. Ohuchi et al reported the cloning of the ngt gene encoding N-glycosyl transferase from L. aerocolonigenes ATCC39243 9) , which is a rebeccamycin producer. They heterologously expressed ngt in Streptomyces lividans and revealed that ngt is responsible for N-glycosylation of the indolocarbazole chromophore, that is, ngt belongs to the rebeccamycin biosynthetic genes.…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of Heterocyclic Antibiotics in Actinomycetes and an Approach to Synthesize the Natural Compounds

Onaka

2006

Actinomycetologica

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Cloning and Expression of a Gene Encoding N-Glycosyltrasferase (ngt) from Saccharothrix aerocolonigenes ATCC39243.

Cited by 31 publications

References 14 publications

Characterization of the Biosynthetic Gene Cluster of Rebeccamycin fromLechevalieria aerocolonigenesATCC 39243

Characterization of the Biosynthetic Gene Cluster of Rebeccamycin fromLechevalieria aerocolonigenesATCC 39243

Engineering biosynthetic pathways to generate antitumor indolocarbazole derivatives

Biosynthesis of Heterocyclic Antibiotics in Actinomycetes and an Approach to Synthesize the Natural Compounds

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