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

Research output: Contribution to journalArticle

44 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology
  • Genetics

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