Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes.
Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes.
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DOI：
10.1021/acs.chemrev.6b00591
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发表时间：
2017-04-26
期刊：
影响因子：
62.1
通讯作者：
van der Donk WA
中科院分区：
文献类型：
--
作者：
Repka LM;Chekan JR;Nair SK;van der Donk WA
羊毛硫肽是核糖体合成和后修饰的肽（RIPPs），其显示出从抗微生物到抗异常性疼痛的多种生物活性。表现出抗微生物活性的羊毛硫肽被称为羊毛硫抗生素。羊毛硫肽的翻译后修饰反应包括Ser和Thr残基脱水为脱氢丙氨酸和脱氢丁酸，这是在不同类别的羊毛硫肽中以三种独特方式进行的转化。在环化过程中，Cys残基然后攻击脱水残基以产生羊毛硫氨酸和甲基羊毛硫氨酸硫醚交联的氨基酸，羊毛硫肽由此得名。所得多环肽具有赋予其生物活性的受限构象。在安装特征性硫醚交联后，定制酶引入额外的翻译后修饰，这些修饰对每种羊毛硫肽是独特的，并且微调它们的活性和/或稳定性。本文综述了近十年来对翻译后修饰酶机制的研究进展。
Lanthipeptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that display a wide variety of biological activities, from antimicrobial to antiallodynic. Lanthipeptides that display antimicrobial activity are called lantibiotics. The post-translational modification reactions of lanthipeptides include dehydration of Ser and Thr residues to dehydroalanine and dehydrobutyrine, a transformation that is carried out in three unique ways in different classes of lanthipeptides. In a cyclization process, Cys residues then attack the dehydrated residues to generate the lanthionine and methyllanthionine thioether cross-linked amino acids from which lanthipeptides derive their name. The resulting polycyclic peptides have constrained conformations that confer their biological activities. After installation of the characteristic thioether cross-links, tailoring enzymes introduce additional post-translational modifications that are unique to each lanthipeptide and that fine-tune their activities and/or stability. This review focuses on studies published over the past decade that have provided much insight into the mechanisms of the enzymes that carry out the post-translational modifications.