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.
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.
Du
L
L
Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
Chen
M
M
Sánchez
C
C
Shen
B
B
D000595:Amino Acid Sequence; D001761:Bleomycin / Q000096:biosynthesis*; D002384:Catalysis; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000378:metabolism*; D016415:Sequence Alignment; D013302:Streptomyces / Q000378:metabolism*; D013379:Substrate Specificity; D013844:Thiazoles / Q000378:metabolism
D013844:Thiazoles; D001761:Bleomycin; D010453:Peptide Synthases