Dissecting Bottromycin Biosynthesis Using Comparative Untargeted Metabolomics.
Dissecting Bottromycin Biosynthesis Using Comparative Untargeted Metabolomics.
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DOI：
10.1002/anie.201604304
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发表时间：
2016-08-08
影响因子：
16.6
通讯作者：
Truman, Andrew W.
中科院分区：
文献类型：
--
作者：
Crone, William J. K.;Vior, Natalia M.;Santos-Aberturas, Javier;Schmitz, Lukas G.;Leeper, Finian J.;Truman, Andrew W.
Bottromycin A2 是一种结构独特的核糖体合成和翻译后修饰肽 (RiPP)，对多重耐药细菌具有有效的抗菌活性。底霉素的结构新颖性源于其前所未有的大环脒和罕见的β-甲基化氨基酸残基。通过调整 btm 基因簇中编码的酶，将前体肽 (BtmD) 的 N 末端转化为 bottromycin A2。然而，人们对这一途径的关键转变知之甚少，包括前所未有的大环化。为了详细了解该途径，利用质谱网络的非靶向代谢组学方法被用来评估一系列途径突变体的代谢组。该分析获得了有关多种先前未表征的生物合成酶功能的关键信息，包括共同催化大环化的 YcaO 结构域蛋白和伴侣蛋白。
Bottromycin A2 is a structurally unique ribosomally synthesized and post‐translationally modified peptide (RiPP) that possesses potent antibacterial activity towards multidrug‐resistant bacteria. The structural novelty of bottromycin stems from its unprecedented macrocyclic amidine and rare β‐methylated amino acid residues. The N‐terminus of a precursor peptide (BtmD) is converted into bottromycin A2 by tailoring enzymes encoded in the btm gene cluster. However, little was known about key transformations in this pathway, including the unprecedented macrocyclization. To understand the pathway in detail, an untargeted metabolomic approach that harnesses mass spectral networking was used to assess the metabolomes of a series of pathway mutants. This analysis has yielded key information on the function of a variety of previously uncharacterized biosynthetic enzymes, including a YcaO domain protein and a partner protein that together catalyze the macrocyclization.
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