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 language | English (US) |
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Pages (from-to) | 171-175 |
Number of pages | 5 |
Journal | FEMS Microbiology Letters |
Volume | 189 |
Issue number | 2 |
DOIs | |
State | Published - Aug 15 2000 |
Keywords
- Biosynthesis
- Bleomycin
- Non-ribosomal peptide synthetase
- Oxidation domain
- Streptomyces verticillus
- Thiazole
ASJC Scopus subject areas
- Microbiology
- Molecular Biology
- Genetics