Biochemical and Spectroscopic Characterization of a Radical S-Adenosyl-l-methionine Enzyme Involved in the Formation of a Peptide Thioether Cross-Link

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• 作者：Nathan A. Bruender ; Jarett Wilcoxen ; R. David Britt ; Vahe Bandarian
• 刊名：Biochemistry
• 出版年：2016
• 出版时间：April 12, 2016
• 年：2016
• 卷：55
• 期：14
• 页码：2122-2134
• 全文大小：624K
• 年卷期：0
• ISSN：1520-4995

文摘

Peptide-derived natural products are a class of metabolites that afford the producing organism a selective advantage over other organisms in their biological niche. While the polypeptide antibiotics produced by the nonribosomal polypeptide synthetases (NRPS) are the most widely recognized, the ss="uu">ribosomally synthesized and ss="uu">post-translationally modified ss="uu">peptidess="uu">s (RiPPs) are an emerging group of natural products with diverse structures and biological functions. Both the NRPS derived peptides and the RiPPs undergo extensive post-translational modifications to produce structural diversity. Here we report the first characterization of the six cysteines in forty-five (SCIFF) [Haft, D. H. and Basu M. K. (2011) J. Bacteriol. 193, 2745–2755] peptide maturase Tte1186, which is a member of the radical S-adenosyl-<span class="smallcaps">lspan>-methionine (SAM) superfamily. Tte1186 catalyzes the formation of a thioether cross-link in the peptide Tte1186a encoded by an orf located upstream of the maturase, under reducing conditions in the presence of SAM. Tte1186 contains three [4Fe-4S] clusters that are indispensable for thioether cross-link formation; however, only one cluster catalyzes the reductive cleavage of SAM. Mechanistic imperatives for the reaction catalyzed by the thioether forming radical SAM maturases will be discussed.