Structural investigation of ribosomally synthesized natural products by hypothetical structure enumeration and evaluation using tandem MS
Structural investigation of ribosomally synthesized natural products by hypothetical structure enumeration and evaluation using tandem MS
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DOI：
10.1073/pnas.1406418111
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发表时间：
2014-08-19
影响因子：
11.1
通讯作者：
van der Donk, Wilfred A.
中科院分区：
文献类型：
--
作者：
Zhang, Qi;Ortega, Manuel;van der Donk, Wilfred A.
核糖体合成和翻译后修饰肽 (RiPP) 是一类不断增长的天然产物，存在于生命的各个领域。这些化合物具有巨大的结构多样性和广泛的生物活性，为探索新型天然产物提供了肥沃的土壤。 RiPP 研究的一个具有挑战性的方面是由于其架构复杂性而难以确定结构。我们在这里描述了一种通过串联质谱法自动表征 RiPP 结构的方法。该方法基于多个质谱的组合分析以及对基于生物合成基因簇和分子量预测的假设结构集合的评估。我们证明该方法对于复杂 RiPP 的结构表征是有效的，包括羊毛硫肽、糖肽和含唑肽。使用这种方法，我们确定了以前结构上未表征的羊毛硫肽原氯绿素 1.2 的结构，并研究了三个生物合成系统中翻译后修饰的顺序。
Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a growing class of natural products that are found in all domains of life. These compounds possess vast structural diversity and have a wide range of biological activities, promising a fertile ground for exploring novel natural products. One challenging aspect of RiPP research is the difficulty of structure determination due to their architectural complexity. We here describe a method for automated structural characterization of RiPPs by tandem mass spectrometry. This method is based on the combined analysis of multiple mass spectra and evaluation of a collection of hypothetical structures predicted based on the biosynthetic gene cluster and molecular weight. We show that this method is effective in structural characterization of complex RiPPs, including lanthipeptides, glycopeptides, and azole-containing peptides. Using this method, we have determined the structure of a previously structurally uncharacterized lanthipeptide, prochlorosin 1.2, and investigated the order of the posttranslational modifications in three biosynthetic systems.