• MeSH
• anthramycin chemie   MeSH
• bakteriální proteiny chemie   MeSH
• katalytická doména MeSH
• kyseliny fenylpyrohroznové chemie   MeSH
• linkomycin chemie   MeSH
• metylace MeSH
• molekulární struktura MeSH
• mutace MeSH
• prolin chemie   MeSH
• Streptomyces chemie   MeSH
• uhlík chemie   MeSH
• vazba proteinů MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthramycin MeSH
• bakteriální proteiny MeSH
• kyseliny fenylpyrohroznové MeSH
• linkomycin MeSH
• phenylpyruvic acid MeSH Prohlížeč
• prolin MeSH
• uhlík MeSH

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.

• MeSH
• anthramycin analogy a deriváty   biosyntéza   chemie   MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• molekulární struktura MeSH
• multigenová rodina * MeSH
• sekvenční analýza MeSH
• Streptomyces chemie   genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthramycin MeSH
• bakteriální proteiny MeSH
• porothramycin A MeSH Prohlížeč

Using anthramycin, a potent antitumor antibiotic produced by Streptomyces refuineus, as an example, we have developed a rational model for the evolution of the capability of this microorganism to produce, tolerate and retain the genetic information needed to make this extremely potent secondary metabolite. The concepts and ideas outlined in this article have also been applied in a more general way to other antibiotics with the hope that this might stimulate research designed to test some of these concepts.

• MeSH
• anthramycin biosyntéza   fyziologie   MeSH
• bakteriální geny MeSH
• biologická evoluce MeSH
• biologické modely MeSH
• Streptomyces genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anthramycin MeSH