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

Liangcheng Du, Mei Chen, César Sánchez, Ben Shen

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41 Citations (Scopus)

Abstract

We have previously proposed that the BlmIV and BlmIII non-ribosomal peptide synthetases are involved in the formation of the bithiazole moiety of the anti-tumor drug bleomycin in Streptomyces verticillus ATCC15003. We report here the identification and characterization of an oxidation domain in BlmIII. The oxidation domain shows local homology to a family of oxidoreductases and is present in all thiazole-forming non-ribosomal peptide synthetase modules known to date. Both the blmIII-Ox domain and blmIII gene were expressed in Escherichia coli, and the resulting BlmIII-Ox and BlmIII proteins were purified to homogeneity. The oxidation domain contains one molar equivalent of non-covalently bound FMN as a prosthetic group. These results provide experimental evidence for an oxidation domain within non- ribosomal peptide synthetases, suggesting that BlmIII-Ox probably catalyzes the thiazoline to thiazole oxidation in bleomycin biosynthesis. (C) 2000 Federation of European Microbiological Societies.

Original languageEnglish (US)
Pages (from-to)171-175
Number of pages5
JournalFEMS Microbiology Letters
Volume189
Issue number2
DOIs
StatePublished - Aug 15 2000

Fingerprint

Peptide Synthases
Thiazoles
Streptomyces
Pharmaceutical Preparations
Flavin Mononucleotide
Neoplasms
Oxidoreductases
Escherichia coli
Genes
indium-bleomycin
Proteins

Keywords

  • Biosynthesis
  • Bleomycin
  • Non-ribosomal peptide synthetase
  • Oxidation domain
  • Streptomyces verticillus
  • Thiazole

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology
  • Genetics

Cite this

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title = "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",
abstract = "We have previously proposed that the BlmIV and BlmIII non-ribosomal peptide synthetases are involved in the formation of the bithiazole moiety of the anti-tumor drug bleomycin in Streptomyces verticillus ATCC15003. We report here the identification and characterization of an oxidation domain in BlmIII. The oxidation domain shows local homology to a family of oxidoreductases and is present in all thiazole-forming non-ribosomal peptide synthetase modules known to date. Both the blmIII-Ox domain and blmIII gene were expressed in Escherichia coli, and the resulting BlmIII-Ox and BlmIII proteins were purified to homogeneity. The oxidation domain contains one molar equivalent of non-covalently bound FMN as a prosthetic group. These results provide experimental evidence for an oxidation domain within non- ribosomal peptide synthetases, suggesting that BlmIII-Ox probably catalyzes the thiazoline to thiazole oxidation in bleomycin biosynthesis. (C) 2000 Federation of European Microbiological Societies.",
keywords = "Biosynthesis, Bleomycin, Non-ribosomal peptide synthetase, Oxidation domain, Streptomyces verticillus, Thiazole",
author = "Liangcheng Du and Mei Chen and C{\'e}sar S{\'a}nchez and Ben Shen",
year = "2000",
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T1 - 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

AU - Du, Liangcheng

AU - Chen, Mei

AU - Sánchez, César

AU - Shen, Ben

PY - 2000/8/15

Y1 - 2000/8/15

N2 - We have previously proposed that the BlmIV and BlmIII non-ribosomal peptide synthetases are involved in the formation of the bithiazole moiety of the anti-tumor drug bleomycin in Streptomyces verticillus ATCC15003. We report here the identification and characterization of an oxidation domain in BlmIII. The oxidation domain shows local homology to a family of oxidoreductases and is present in all thiazole-forming non-ribosomal peptide synthetase modules known to date. Both the blmIII-Ox domain and blmIII gene were expressed in Escherichia coli, and the resulting BlmIII-Ox and BlmIII proteins were purified to homogeneity. The oxidation domain contains one molar equivalent of non-covalently bound FMN as a prosthetic group. These results provide experimental evidence for an oxidation domain within non- ribosomal peptide synthetases, suggesting that BlmIII-Ox probably catalyzes the thiazoline to thiazole oxidation in bleomycin biosynthesis. (C) 2000 Federation of European Microbiological Societies.

AB - We have previously proposed that the BlmIV and BlmIII non-ribosomal peptide synthetases are involved in the formation of the bithiazole moiety of the anti-tumor drug bleomycin in Streptomyces verticillus ATCC15003. We report here the identification and characterization of an oxidation domain in BlmIII. The oxidation domain shows local homology to a family of oxidoreductases and is present in all thiazole-forming non-ribosomal peptide synthetase modules known to date. Both the blmIII-Ox domain and blmIII gene were expressed in Escherichia coli, and the resulting BlmIII-Ox and BlmIII proteins were purified to homogeneity. The oxidation domain contains one molar equivalent of non-covalently bound FMN as a prosthetic group. These results provide experimental evidence for an oxidation domain within non- ribosomal peptide synthetases, suggesting that BlmIII-Ox probably catalyzes the thiazoline to thiazole oxidation in bleomycin biosynthesis. (C) 2000 Federation of European Microbiological Societies.

KW - Biosynthesis

KW - Bleomycin

KW - Non-ribosomal peptide synthetase

KW - Oxidation domain

KW - Streptomyces verticillus

KW - Thiazole

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