Sequence analysis of porothramycin biosynthetic gene cluster

0435283 - MBÚ 2015 RIV CZ eng J - Journal Article
Najmanová, Lucie - Ulanová, Dana - Jelínková, Markéta - Kameník, Zdeněk - Kettnerová, Eliška - Koběrská, Markéta - Gažák, Radek - Radojevič, Bojana - Janata, Jiří
Sequence analysis of porothramycin biosynthetic gene cluster.
Folia Microbiologica. Roč. 59, č. 6 (2014), s. 543-552. ISSN 0015-5632. E-ISSN 1874-9356
R&D Projects: GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) EE2.3.20.0055; GA MŠMT(CZ) EE2.3.30.0003
Institutional support: RVO:61388971
Keywords : BIOLOGICAL-ACTIVITY * ANTHRAMYCIN * SPECIFICITY
Subject RIV: EE - Microbiology, Virology
Impact factor: 1.000, year: 2014

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.
Permanent Link: http://hdl.handle.net/11104/0239210