Repka Lindsay M, Chekan Jonathan R, Nair Satish K, van der Donk Wilfred A
Howard Hughes Medical Institute and Department of Chemistry, ‡Department of Biochemistry, and §Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
Chem Rev. 2017 Apr 26;117(8):5457-5520. doi: 10.1021/acs.chemrev.6b00591. Epub 2017 Jan 30.
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.
羊毛硫肽是核糖体合成且经翻译后修饰的肽（RiPPs），具有广泛的生物活性，从抗菌到抗痛觉过敏。具有抗菌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丝氨酸和苏氨酸残基脱水生成脱氢丙氨酸和脱氢丁氨酸，这种转化在不同类别的羊毛硫肽中以三种独特方式进行。在环化过程中，半胱氨酸残基随后攻击脱水残基，生成羊毛硫氨酸和甲基羊毛硫氨酸硫醚交联氨基酸，羊毛硫肽由此得名。所得的多环肽具有受限构象，赋予它们生物活性。在安装特征性硫醚交联后，修饰酶引入额外的翻译后修饰，这些修饰对每种羊毛硫肽而言都是独特的，并且可以微调它们的活性和/或稳定性。本综述聚焦于过去十年发表的研究，这些研究为进行翻译后修饰的酶的作用机制提供了很多见解。
