title: The genome sequence of Streptomyces lividans 66 reveals a novel tRNA-dependent peptide biosynthetic system within a metal-related genomic island.
abstract: The complete genome sequence of the original isolate of the model actinomycete Streptomyces lividans 66, also referred to as 1326, was deciphered after a combination of next-generation sequencing platforms and a hybrid assembly pipeline. Comparative analysis of the genomes of S. lividans 66 and closely related strains, including S. coelicolor M145 and S. lividans TK24, was used to identify strain-specific genes. The genetic diversity identified included a large genomic island with a mosaic structure, present in S. lividans 66 but not in the strain TK24. Sequence analyses showed that this genomic island has an anomalous (G + C) content, suggesting recent acquisition and that it is rich in metal-related genes. Sequences previously linked to a mobile conjugative element, termed plasmid SLP3 and defined here as a 94 kb region, could also be identified within this locus. Transcriptional analysis of the response of S. lividans 66 to copper was used to corroborate a role of this large genomic island, including two SLP3-borne "cryptic" peptide biosynthetic gene clusters, in metal homeostasis. Notably, one of these predicted biosynthetic systems includes an unprecedented nonribosomal peptide synthetase--tRNA-dependent transferase biosynthetic hybrid organization. This observation implies the recruitment of members of the leucyl/phenylalanyl-tRNA-protein transferase family to catalyze peptide bond formation within the biosynthesis of natural products. Thus, the genome sequence of S. lividans 66 not only explains long-standing genetic and phenotypic differences but also opens the door for further in-depth comparative genomic analyses of model Streptomyces strains, as well as for the discovery of novel natural products following genome-mining approaches.
authors.affiliation: Evolution of Metabolic Diversity Laboratory, Laboratorio Nacional de Genómica para la Biodiversidad, Langebio, Cinvestav-IPN, Irapuato, México.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cruz-Morales
authors.forename: Erik
authors.initials: E
authors.lastname: Vijgenboom
authors.forename: Fernanda
authors.initials: F
authors.lastname: Iruegas-Bocardo
authors.forename: Geneviève
authors.initials: G
authors.lastname: Girard
authors.forename: Luis Alfonso
authors.initials: LA
authors.lastname: Yáñez-Guerra
authors.forename: Hilda E
authors.initials: HE
authors.lastname: Ramos-Aboites
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pernodet
authors.forename: Jozef
authors.initials: J
authors.lastname: Anné
authors.forename: Gilles P
authors.initials: GP
authors.lastname: van Wezel
authors.forename: Francisco
authors.initials: F
authors.lastname: Barona-Gómez
mesh_terms: D003300:Copper / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D044404:Genomic Islands; D010455:Peptides / Q000378:metabolism; D014176:Protein Biosynthesis; D012329:RNA, Bacterial / Q000235:genetics*; D012343:RNA, Transfer / Q000235:genetics*; D048372:Streptomyces coelicolor / Q000235:genetics; D048170:Streptomyces lividans / Q000235:genetics* / Q000378:metabolism
chemical_list: D010455:Peptides; D012329:RNA, Bacterial; D003300:Copper; D012343:RNA, Transfer
keywords: L/F tRNA transferase; Streptomyces comparative genomics; bacterial next-generation genome sequencing; copper homeostasis; peptide biosynthesis