Isolation and characterization of the gene cluster for biosynthesis of the thiopeptide antibiotic TP-1161.
Recently, we isolated a new thiopeptide antibiotic, TP-1161, from the fermentation broth of a marine actinomycete typed as a member of the genus Nocardiopsis. Here we report the identification, isolation, and analysis of the TP-1161 biosynthetic gene cluster from this species. The gene cluster was identified by mining a draft genome sequence using the predicted structural peptide sequence of TP-1161. Functional assignment of a ∼16-kb genomic region revealed 13 open reading frames proposed to constitute the TP-1161 biosynthetic locus. While the typical core set of thiopeptide modification enzymes contains one cyclodehydratase/dehydrogenase pair, paralogous genes predicted to encode additional cyclodehydratases and dehydrogenases were identified. Although attempts at heterologous expression of the TP-1161 gene cluster in Streptomyces coelicolor failed, its identity was confirmed through the targeted gene inactivation in the original host.
Engelhardt
Kerstin
K
Department of Biotechnology, Norwegian University of Science and Technology, Sem Sælandsvei 6/8, 7491 Trondheim, Norway.
Degnes
Kristin F
KF
Zotchev
Sergey B
SB
D000192:Actinomycetales / Q000235:genetics* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003360:Cosmids / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D010455:Peptides / Q000235:genetics; D010456:Peptides, Cyclic / Q000096:biosynthesis*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013844:Thiazoles
D000900:Anti-Bacterial Agents; D010455:Peptides; D010456:Peptides, Cyclic; C555532:TP 1161; D013844:Thiazoles