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The biosynthetic gene cluster for the antitumor rebeccamycin: characterization and generation of indolocarbazole derivatives.
- C. Sánchez, I. Butovich, A. Braña, J. Rohr, C. Méndez, J. Salas
- Medicine, Biology
- Chemistry & biology
- 1 April 2002
The cloned genes should help to elucidate the molecular basis for indolocarbazole biosynthesis and set the stage for the generation of novel indolo-rebeccamycin analogues by genetic engineering. Expand
Hybrid peptide-polyketide natural products: biosynthesis and prospects toward engineering novel molecules.
It is shown that the same catalytic sites are conserved between the hybrid NRPS-PKS and normal NRPS or PKS systems, although the ketoacyl synthase domain in NRPS/PKS hybrids is unique, and that specific interpolypeptide linkers exist at both the C- and N-termini of the NRPS and PKS proteins. Expand
Cloning and characterization of a phosphopantetheinyl transferase from Streptomyces verticillus ATCC15003, the producer of the hybrid peptide-polyketide antitumor drug bleomycin.
The development of a PCR method for cloning SFP-type PPTases from actinomycetes, the recognition of the Sfp-typePPTases to be associated with secondary metabolism with a relaxed carrier protein specificity, and the availability of Svp, in addition to Sfp, should facilitate future endeavors in engineered biosynthesis of peptide, polyketide, and, in particular, hybrid peptide-polyketide natural products. Expand
The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide…
The blm gene cluster is characterized by a hybrid NRPS-PKS system, supporting the wisdom of combining individual NRPS and PKS modules for combinatorial biosynthesis. Expand
Reevaluation of the Violacein Biosynthetic Pathway and its Relationship to Indolocarbazole Biosynthesis
- C. Sánchez, A. Braña, C. Méndez, J. Salas
- Biology, Medicine
- Chembiochem : a European journal of chemical…
- 4 August 2006
The violacein pathway is studied through expression of vio genes in Escherichia coli and Streptomyces albus and a pair of genes (vioAB) was functionally equivalent to the homologous pair in the indolocarbazole pathway (rebOD), directing the formation of chromopyrrolic acid. Expand
Combinatorial biosynthesis of antitumor indolocarbazole compounds.
- C. Sánchez, Lili Zhu, +4 authors J. Salas
- Biology, Medicine
- Proceedings of the National Academy of Sciences…
- 11 January 2005
A biological process based on combinatorial biosynthesis for the production of indolocarbazole compounds (or their precursors) in engineered microorganisms as a complementary approach to chemical synthesis is reported. Expand
Indolocarbazole natural products: occurrence, biosynthesis, and biological activity.
The indolocarbazole family of natural products, including the biosynthetically related bisindolylmaleimides, is reviewed, with an emphasis on the development of analogs that have entered clinical trials for its future use against cancer or other diseases. Expand
Deciphering the late steps in the biosynthesis of the anti‐tumour indolocarbazole staurosporine: sugar donor substrate flexibility of the StaG glycosyltransferase
Staurosporine biosynthesis was reconstituted in vivo in a heterologous host Streptomyces albus by using two different plasmids: the ‘aglycone vector’ expressing a set of genes involved in indolocarbazole biosynthesis together with staG (encoding a glycosyltransferase) and/or staN (coding for a P450 oxygenase). Expand
Bleomycin Biosynthesis inStreptomyces verticillusATCC15003: A Model of Hybrid Peptide and Polyketide Biosynthesis☆☆☆★
Abstract The biosynthesis of bleomycins (BLMs) in Streptomyces verticillus ( Sv ) ATCC15003 was reviewed. Early biosynthetic studies by incorporation of isotope-labeled precursors and by isolation of… Expand
An oxidation domain in the BlmIII non-ribosomal peptide synthetase probably catalyzing thiazole formation in the biosynthesis of the anti-tumor drug bleomycin in Streptomyces verticillus ATCC15003.
Experimental evidence for an oxidation domain within non-ribosomal peptide synthetases is provided, suggesting that BlmIII-Ox probably catalyzes the thiazoline to thiazole oxidation in bleomycin biosynthesis. Expand