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.

• Authors: L Du, M Chen, C Sánchez, B Shen
• Journal: FEMS microbiology letters (FEMS Microbiol Lett) Vol. 189 Issue 2 Pg. 171-5 (Aug 15 2000) ISSN: 0378-1097 [Print] England
• PMID: 10930733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Thiazoles
• Bleomycin
• Peptide Synthases

Topics

• Amino Acid Sequence
• Bleomycin (biosynthesis)
• Catalysis
• Molecular Sequence Data
• Peptide Synthases (metabolism)
• Sequence Alignment
• Streptomyces (metabolism)
• Substrate Specificity
• Thiazoles (metabolism)