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Sequence analysis of porothramycin biosynthetic gene cluster

The biosynthetic gene cluster of porothramycin, a sequence-selective DNA alkylating compound, was identified in the genome of producing strain Streptomyces albus subsp. albus (ATCC 39897) and sequentially characterized. A 39.7 kb long DNA region contains 27 putative genes, 18 of them revealing high...

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Autores principales: Najmanova, Lucie, Ulanova, Dana, Jelinkova, Marketa, Kamenik, Zdenek, Kettnerova, Eliska, Koberska, Marketa, Gazak, Radek, Radojevic, Bojana, Janata, Jiri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194701/
https://www.ncbi.nlm.nih.gov/pubmed/25128200
http://dx.doi.org/10.1007/s12223-014-0339-x
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author Najmanova, Lucie
Ulanova, Dana
Jelinkova, Marketa
Kamenik, Zdenek
Kettnerova, Eliska
Koberska, Marketa
Gazak, Radek
Radojevic, Bojana
Janata, Jiri
author_facet Najmanova, Lucie
Ulanova, Dana
Jelinkova, Marketa
Kamenik, Zdenek
Kettnerova, Eliska
Koberska, Marketa
Gazak, Radek
Radojevic, Bojana
Janata, Jiri
author_sort Najmanova, Lucie
collection PubMed
description The biosynthetic gene cluster of porothramycin, a sequence-selective DNA alkylating compound, was identified in the genome of producing strain Streptomyces albus subsp. albus (ATCC 39897) and sequentially characterized. A 39.7 kb long DNA region contains 27 putative genes, 18 of them revealing high similarity with homologous genes from biosynthetic gene cluster of closely related pyrrolobenzodiazepine (PBD) compound anthramycin. However, considering the structures of both compounds, the number of differences in the gene composition of compared biosynthetic gene clusters was unexpectedly high, indicating participation of alternative enzymes in biosynthesis of both porothramycin precursors, anthranilate, and branched L-proline derivative. Based on the sequence analysis of putative NRPS modules Por20 and Por21, we suppose that in porothramycin biosynthesis, the methylation of anthranilate unit occurs prior to the condensation reaction, while modifications of branched proline derivative, oxidation, and dimethylation of the side chain occur on already condensed PBD core. Corresponding two specific methyltransferase encoding genes por26 and por25 were identified in the porothramycin gene cluster. Surprisingly, also methyltransferase gene por18 homologous to orf19 from anthramycin biosynthesis was detected in porothramycin gene cluster even though the appropriate biosynthetic step is missing, as suggested by ultra high-performance liquid chromatography-diode array detection-mass spectrometry (UHPLC-DAD-MS) analysis of the product in the S. albus culture broth.
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spelling pubmed-41947012014-10-16 Sequence analysis of porothramycin biosynthetic gene cluster Najmanova, Lucie Ulanova, Dana Jelinkova, Marketa Kamenik, Zdenek Kettnerova, Eliska Koberska, Marketa Gazak, Radek Radojevic, Bojana Janata, Jiri Folia Microbiol (Praha) Article The biosynthetic gene cluster of porothramycin, a sequence-selective DNA alkylating compound, was identified in the genome of producing strain Streptomyces albus subsp. albus (ATCC 39897) and sequentially characterized. A 39.7 kb long DNA region contains 27 putative genes, 18 of them revealing high similarity with homologous genes from biosynthetic gene cluster of closely related pyrrolobenzodiazepine (PBD) compound anthramycin. However, considering the structures of both compounds, the number of differences in the gene composition of compared biosynthetic gene clusters was unexpectedly high, indicating participation of alternative enzymes in biosynthesis of both porothramycin precursors, anthranilate, and branched L-proline derivative. Based on the sequence analysis of putative NRPS modules Por20 and Por21, we suppose that in porothramycin biosynthesis, the methylation of anthranilate unit occurs prior to the condensation reaction, while modifications of branched proline derivative, oxidation, and dimethylation of the side chain occur on already condensed PBD core. Corresponding two specific methyltransferase encoding genes por26 and por25 were identified in the porothramycin gene cluster. Surprisingly, also methyltransferase gene por18 homologous to orf19 from anthramycin biosynthesis was detected in porothramycin gene cluster even though the appropriate biosynthetic step is missing, as suggested by ultra high-performance liquid chromatography-diode array detection-mass spectrometry (UHPLC-DAD-MS) analysis of the product in the S. albus culture broth. Springer Netherlands 2014-08-16 2014 /pmc/articles/PMC4194701/ /pubmed/25128200 http://dx.doi.org/10.1007/s12223-014-0339-x Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Article
Najmanova, Lucie
Ulanova, Dana
Jelinkova, Marketa
Kamenik, Zdenek
Kettnerova, Eliska
Koberska, Marketa
Gazak, Radek
Radojevic, Bojana
Janata, Jiri
Sequence analysis of porothramycin biosynthetic gene cluster
title Sequence analysis of porothramycin biosynthetic gene cluster
title_full Sequence analysis of porothramycin biosynthetic gene cluster
title_fullStr Sequence analysis of porothramycin biosynthetic gene cluster
title_full_unstemmed Sequence analysis of porothramycin biosynthetic gene cluster
title_short Sequence analysis of porothramycin biosynthetic gene cluster
title_sort sequence analysis of porothramycin biosynthetic gene cluster
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194701/
https://www.ncbi.nlm.nih.gov/pubmed/25128200
http://dx.doi.org/10.1007/s12223-014-0339-x
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