The Greater Celandine: Identification and Characterization of an Antimicrobial Peptide from Chelidonium majus.
The Greater Celandine: Identification and Characterization of an Antimicrobial Peptide from Chelidonium majus.
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DOI：
10.1021/acs.jnatprod.3c00939
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发表时间：
2024-02
影响因子：
5.1
通讯作者：
Patric W. Sadecki;Garrett D Laws;Johnathon J Morgan;A. Wommack;R. Nawrot;Leslie M Hicks
中科院分区：
文献类型：
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作者：
Patric W. Sadecki;Garrett D Laws;Johnathon J Morgan;A. Wommack;R. Nawrot;Leslie M Hicks
白屈菜，被称为大白屈菜，是一种含有乳胶的植物，因其抗癌和抗菌特性而被利用。在此，C.主要的气生组织被挖掘出抗微生物肽的存在。一种高度丰富的富含半胱氨酸的肽，长度为25个氨基酸，被认为是CM-AMP 1，通过多种质谱方法进行表征。利用电子活化解离来区分异亮氨酸和亮氨酸残基，并补充常规碰撞诱导解离以获得全长肽的全序列覆盖。CM-AMP 1与公开数据库中的任何蛋白质几乎没有序列相似性，突出了其半胱氨酸景观和核心基序的新奇。天然肽中三个二硫键的存在赋予蛋白水解稳定性，并且在半胱氨酸残基的烷基化后，抗微生物活性大大降低。CM-AMP 1的合成变体用于确认全长序列和核心基序的活性。为了评估生物学影响，E.大肠杆菌生长在亚致死浓度的CM-AMP 1和定量蛋白质组学被用来确定蛋白质产生的细菌在压力下，最终表明膜溶解抗菌作用机制。本研究整合了多种分析方法，用于从C. majus。
Chelidonium majus, known as Greater Celandine, is a latex-bearing plant that has been leveraged for its anticancer and antimicrobial properties. Herein, C. majus aerial tissue is mined for the presence of antimicrobial peptides. A highly abundant cysteine-rich peptide with a length of 25 amino acids, deemed CM-AMP1, is characterized through multiple mass spectrometric approaches. Electron-activated dissociation is leveraged to differentiate between isoleucine and leucine residues and complement conventional collision-induced dissociation to gain full sequence coverage of the full-length peptide. CM-AMP1 shares little sequence similarity with any proteins in publicly available databases, highlighting the novelty of its cysteine landscape and core motif. The presence of three disulfide bonds in the native peptide confers proteolytic stability, and antimicrobial activity is greatly decreased upon the alkylation of the cysteine residues. Synthetic variants of CM-AMP1 are used to confirm the activity of the full-length sequence and the core motif. To assess the biological impact, E. coli was grown in a sublethal concentration of CM-AMP1 and quantitative proteomics was used to identify proteins produced by the bacteria under stress, ultimately suggesting a membrane lytic antimicrobial mechanism of action. This study integrates multiple analytical methods for molecular and biological characterization of a unique antimicrobial peptide identified from C. majus.