Caulosegnins I-III: A Highly Diverse Group of Lasso Peptides Derived from a Single Biosynthetic Gene Cluster
Caulosegnins I-III: A Highly Diverse Group of Lasso Peptides Derived from a Single Biosynthetic Gene Cluster
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DOI：
10.1021/ja308173b
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发表时间：
2013-01-09
影响因子：
15
通讯作者：
Marahiel, Mohamed A.
中科院分区：
文献类型：
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作者：
Hegemann, Julian D.;Zimmermann, Marcel;Marahiel, Mohamed A.
Lasso 肽是核糖体来源的天然产物，具有独特的打结结构折叠。尽管已知的只有少数，但最近关于新分离出的套索肽的报道却很少。在这项工作中，我们报告了从 Caulobacter segnis 中鉴定出一种新型套索肽基因簇，该基因簇使用单一生物合成机制产生三种新的套索肽（caulosegnins I、II 和 III）。这些套索肽具有不同的环大小和氨基酸序列。在这项研究中，我们开发了一种增强套索肽生产的系统，以便通过在大肠杆菌中异源表达来分离这些化合物。我们能够通过核磁共振波谱分析阐明最丰富的套索肽 caulosegnin I 的结构，并进行彻底的突变分析，深入了解其生物合成，并揭示影响套索折叠稳定性的重要因素。当受到热变性时，茎秆素也表现出不同的行为，这是特殊的，因为所有套索肽都被认为具有内在的高热稳定性。
Lasso peptides are natural products ribosomal origin with a unique knotted structural fold. Even though only a few of them are known, recent reports of newly isolated lasso peptides were scarce. In this work, we report the identification of a novel lasso peptide gene cluster from Caulobacter segnis, that produces three new lasso peptides (caulosegnins I, II, and III) using a single biosynthetic machinery. These lasso peptides possess different ring sizes and amino acid sequences. In this study, we have developed a system for enhanced lasso peptide production to allow isolation of these compounds through heterologous expression in Escherichia coli. We were able to elucidate the structure of the most abundant lasso peptide caulosegnin I via NMR spectroscopic analysis and performed a thorough mutational analysis that gave insight into their biosynthesis and revealed important factors affecting the stabilization of the lasso fold in general. The caulosegnins also show a diverse behavior when subjected to thermal denaturation, which is exceptional as all lasso peptides were believed to have an intrinsic high thermal stability.