Characterization of the biosynthetic gene cluster (ata) for the A201A aminonucleoside antibiotic from Saccharothrix mutabilis subsp. capreolus

Antibiotic A201A produced by Saccharothrix mutabilis subsp. capreolus NRRL3817 contains an aminonucleoside ( N 6 , N 6 -dimethyl-3′-amino-3′-deoxyadenosyl), a polyketide ( α -methyl- p -coumaric acid) and a disaccharide moiety. The heterologous expression in Streptomyces lividans and Streptomyces co...

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Veröffentlicht in:Journal of antibiotics 2017-04, Vol.70 (4), p.404-413
Hauptverfasser: Saugar, Irene, Molloy, Brian, Sanz, Eloisa, Blanca Sánchez, María, Fernández-Lobato, María, Jiménez, Antonio
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container_title Journal of antibiotics
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creator Saugar, Irene
Molloy, Brian
Sanz, Eloisa
Blanca Sánchez, María
Fernández-Lobato, María
Jiménez, Antonio
description Antibiotic A201A produced by Saccharothrix mutabilis subsp. capreolus NRRL3817 contains an aminonucleoside ( N 6 , N 6 -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.
doi_str_mv 10.1038/ja.2016.123
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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. 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subjects 38/22
45/23
45/41
631/45
631/61
82/16
Actinomycetales - genetics
Amino Acid Sequence
Aminoglycosides - biosynthesis
Aminoglycosides - genetics
Anti-Bacterial Agents - biosynthesis
Antibiotics
Bacteriology
Base Sequence
Biomedical and Life Sciences
Bioorganic Chemistry
Biosynthesis
Computational Biology
Coumaric acid
Disaccharides
Disaccharides - biosynthesis
Disaccharides - genetics
Gene Targeting
Genes
Inactivation
Life Sciences
Medicinal Chemistry
Methyltransferase
Methyltransferases - genetics
Microbiology
Multigene Family - genetics
Nucleotide sequence
Nucleotides
Oligonucleotides - chemistry
Open reading frames
Organic Chemistry
original-article
p-Coumaric acid
Plasmids
Polyketides - metabolism
Streptomyces - genetics
Streptomyces - metabolism
title Characterization of the biosynthetic gene cluster (ata) for the A201A aminonucleoside antibiotic from Saccharothrix mutabilis subsp. capreolus
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