title: Characterization of the biosynthetic gene cluster (ata) for the A201A aminonucleoside antibiotic from Saccharothrix mutabilis subsp. capreolus.
abstract: Antibiotic A201A produced by Saccharothrix mutabilis subsp. capreolus NRRL3817 contains an aminonucleoside (N6, N6-dimethyl-3'-amino-3'-deoxyadenosyl), a polyketide (α-methyl-p-coumaric acid) and a disaccharide moiety. The heterologous expression in Streptomyces lividans and Streptomyces coelicolor of a S. mutabilis genomic region of ~34 kb results in the production of A201A, which was identified by microbiological, biochemical and physicochemical approaches, and indicating that this region may contain the entire A201A biosynthetic gene cluster (ata). The analysis of the nucleotide sequence of the fragment reveals the presence of 32 putative open reading frames (ORF), 28 of which according to boundary gene inactivation experiments are likely to be sufficient for A201A biosynthesis. Most of these ORFs could be assigned to the biosynthesis of the antibiotic three structural moieties. Indeed, five ORFs had been previously implicated in the biosynthesis of the aminonucleoside moiety, at least nine were related to the biosynthesis of the polyketide (ata-PKS1-ataPKS4, ata18, ata19, ata2, ata4 and ata7) and six were associated with the synthesis of the disaccharide (ata12, ata13, ata16, ata17, ata5 and ata10) moieties. In addition to AtaP5, three putative methyltransferase genes are also found in the ata cluster (Ata6, Ata8 and Ata11), and no regulatory genes were found.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Saugar
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco Madrid, Spain.
authors.forename: Brian
authors.initials: B
authors.lastname: Molloy
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco Madrid, Spain.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Sanz
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Blanca Sánchez
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Fernández-Lobato
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jiménez
mesh_terms: D000192:Actinomycetales / Q000235:genetics*; D000595:Amino Acid Sequence; D000617:Aminoglycosides / Q000096:biosynthesis* / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001483:Base Sequence; D019295:Computational Biology; D004187:Disaccharides / Q000096:biosynthesis / Q000235:genetics; D018390:Gene Targeting; D008780:Methyltransferases / Q000235:genetics; D005810:Multigene Family / Q000235:genetics*; D009841:Oligonucleotides / Q000737:chemistry; D010957:Plasmids; D061065:Polyketides / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004187:Disaccharides; D009841:Oligonucleotides; D061065:Polyketides; C046076:A 201A; D008780:Methyltransferases