reading 8 final

reading 8 final - and SAMR0918 was predicted to code for a...

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Chem 157 In the paper “An Iterative Nonoribosomal Peptide Synthetase Assembles the Pyrrole- Amide Antibiotic Congocidine in Streptomyces ambofaciens,” the authors demonstrated a proposed mechanism of the biosynthesis of pyrrole-amide antibiotic congocidine as well as the involvement of nonoribosomal peptide synthetase (NRPS). Congocidine, a member of the pyrrole-amide family, has the ability to bind to the minor groove of DNA double helix and therefore has antiviral, antibiotic, and antitumor activities. The authors first sequenced the linear chromosome of S. ambofaciens and postulate that the gene cluster found in the arm of the chromosome directs the congocidine biosynthesis. By using gene deletion studies and LC-MS and HPLC analyses, the authors were able to found that inactivation of SAMR0901 gene cluster results in abolished congocidine and that SAMR0898-0921 constitute congocidine biosynthesis gene cluster. Moreover, SAMR0920 and 0919 were predicted to give resistance to congocidine
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Unformatted text preview: and SAMR0918 was predicted to code for a protein that regulates congocidine biosynthesis. The rest of the 19 genes direct either the biosynthesis of congocidine precursor or the assembly of the molecule. However, later the authors found that this gene cluster is not involved in the biosynthesis of the three congocidine precursors but NRPS was observed to catalyze the amide bonds formation between the precursors and the 4 genes that code for NRPS has been identified. One significant proposal of the paper is the assembly of congosidine. Activated pyrrol precursors are first transferred to cgc18_A PCP and cgc19, condensation then takes place to form bipyrrole molecule. The addition of other 2 activated precursors is catalyzed by cgc2 and 16, followed by N-methylation by cgc15. In sum, the paper is very straight forward and easy to understand. The authors postulates are fairly convincing due to detailed experimental procedures and results....
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