Title of article :
Benzodiazepine Biosynthesis in Streptomyces refuineus Original Research Article
Author/Authors :
Yunfeng Hu، نويسنده , , Vanessa Phelan، نويسنده , , Ioanna Ntai، نويسنده , , Chris M. Farnet، نويسنده , , Emmanuel Zazopoulos، نويسنده , , Brian O. Bachmann، نويسنده ,
Issue Information :
ماهنامه با شماره پیاپی سال 2007
Pages :
11
From page :
691
To page :
701
Abstract :
Anthramycin is a benzodiazepine alkaloid with potent antitumor and antibiotic activity produced by the thermophilic actinomycete Streptomyces refuineus sbsp. thermotolerans. In this study, the complete 32.5 kb gene cluster for the biosynthesis of anthramycin was identified by using a genome-scanning approach, and cluster boundaries were estimated via comparative genomics. A λ-RED-mediated gene-replacement system was developed to provide supporting evidence for critical biosynthetic genes and to validate the boundaries of the proposed anthramycin gene cluster. Sequence analysis reveals that the 25 open reading frame anthramycin cluster contains genes consistent with the biosynthesis of the two halves of anthramycin: 4 methyl-3-hydroxyanthranilic acid and a “dehydroproline acrylamide” moiety. These nonproteinogenic amino acid precursors are condensed by a two-module nonribosomal peptide synthetase (NRPS) terminated by a reductase domain, consistent with the final hemiaminal oxidation state of anthramycin.
Journal title :
Chemistry and Biology
Serial Year :
2007
Journal title :
Chemistry and Biology
Record number :
1159384
Link To Document :
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