Identification of a Napsamycin Biosynthesis Gene Cluster by Genome Mining
| Autor: | Xiaoyu Tang, Bertolt Gust, Katharina Sedding, Emmanuel Wemakor, Stefanie Siebenberg, Susanne Hennig, Leonard Kaysser |
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| Rok vydání: | 2010 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Biochemistry Streptomyces chemistry.chemical_compound Biosynthesis Multienzyme Complexes Gene cluster Amino Acid Sequence Cloning Molecular Peptide Synthases Uracil Molecular Biology Gene Peptide sequence Chromatography High Pressure Liquid Methionine biology Organic Chemistry Streptomyces coelicolor Nucleosides biology.organism_classification Anti-Bacterial Agents chemistry Multigene Family Tyrosine Molecular Medicine Heterologous expression Peptides Genome Bacterial Antimicrobial Cationic Peptides |
| Zdroj: | ChemBioChem. 12:477-487 |
| ISSN: | 1439-4227 |
| Popis: | Napsamycins are potent inhibitors of bacterial translocase I, an essential enzyme in peptidoglycan biosynthesis, and are classified as uridylpeptide antibiotics. They comprise an N-methyl diaminobutyric acid, an ureido group, a methionine and two non-proteinogenic aromatic amino acid residues in a peptide backbone that is linked to a 5'-amino-3'-deoxyuridine by an unusual enamide bond. The napsamycin gene cluster was identified in Streptomyces sp. DSM5940 by using PCR probes from a putative uridylpeptide biosynthetic cluster found in S. roseosporus NRRL15998 by genome mining. Annotation revealed 29 hypothetical genes encoding for resistance, regulation and biosynthesis of the napsamycins. Analysis of the gene cluster indicated that the peptide core structure is assembled by a nonlinear non-ribosomal peptide synthetase (NRPS)-like mechanism that involves several discrete single or didomain proteins. Some genes could be assigned, for example, to the synthesis of the N-methyl diaminobutyric acid, to the generation of m-tyrosine and to the reduction of the uracil moiety. The heterologous expression of the gene cluster in Streptomyces coelicolor M1154 resulted in the production of napsamycins and mureidomycins as demonstrated by LC-ESI-MS and MS/MS analysis. The napsamycin gene cluster provides a molecular basis for the detailed study of the biosynthesis of this class of structurally unusual compounds. |
| Databáze: | OpenAIRE |
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