Burkhart Brandon J, Schwalen Christopher J, Mann Greg, Naismith James H, Mitchell Douglas A
Biomedical Science Research Complex, University of St Andrews , BSRC North Haugh, St Andrews KY16 9ST, United Kingdom.
State Key Laboratory of Biotherapy, Sichuan University , Sichuan, China.
Chem Rev. 2017 Apr 26;117(8):5389-5456. doi: 10.1021/acs.chemrev.6b00623. Epub 2017 Mar 3.
With advances in sequencing technology, uncharacterized proteins and domains of unknown function (DUFs) are rapidly accumulating in sequence databases and offer an opportunity to discover new protein chemistry and reaction mechanisms. The focus of this review, the formerly enigmatic YcaO superfamily (DUF181), has been found to catalyze a unique phosphorylation of a ribosomal peptide backbone amide upon attack by different nucleophiles. Established nucleophiles are the side chains of Cys, Ser, and Thr which gives rise to azoline/azole biosynthesis in ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products. However, much remains unknown about the potential for YcaO proteins to collaborate with other nucleophiles. Recent work suggests potential in forming thioamides, macroamidines, and possibly additional post-translational modifications. This review covers all knowledge through mid-2016 regarding the biosynthetic gene clusters (BGCs), natural products, functions, mechanisms, and applications of YcaO proteins and outlines likely future research directions for this protein superfamily.
随着测序技术的进步，未表征的蛋白质和功能未知结构域（DUFs）在序列数据库中迅速积累，为发现新的蛋白质化学和反应机制提供了契机。本综述的重点——曾经神秘的YcaO超家族（DUF181），已被发现可催化核糖体肽主链酰胺在受到不同亲核试剂攻击时发生独特的磷酸化反应。已确定的亲核试剂是半胱氨酸、丝氨酸和苏氨酸的侧链，它们在核糖体合成及翻译后修饰肽（RiPP）天然产物中引发唑啉/唑的生物合成。然而，关于YcaO蛋白与其他亲核试剂协同作用的潜力仍有许多未知之处。近期研究表明其在形成硫代酰胺、大脒以及可能的其他翻译后修饰方面具有潜力。本综述涵盖了截至2016年年中有关YcaO蛋白的生物合成基因簇（BGCs）、天然产物、功能、机制及应用的所有知识，并概述了该蛋白质超家族未来可能的研究方向。
