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.

中文翻译：

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依赖 YcaO 的翻译后酰胺活化：生物合成、结构和功能

随着测序技术的进步，未表征的蛋白质和未知功能域 (DUF) 正在序列数据库中迅速积累，并为发现新的蛋白质化学和反应机制提供了机会。这篇综述的重点是以前神秘的 YcaO 超家族 (DUF181)，它被发现在受到不同亲核试剂攻击时催化核糖体肽骨架酰胺的独特磷酸化。已建立的亲核试剂是 Cys、Ser 和 Thr 的侧链，在核糖体合成和翻译后修饰肽 (RiPP) 天然产物中产生唑啉/唑生物合成。然而，关于 YcaO 蛋白与其他亲核试剂合作的潜力仍然未知。最近的工作表明有可能形成硫代酰胺、大脒、可能还有额外的翻译后修饰。这篇综述涵盖了截至 2016 年年中关于 YcaO 蛋白的生物合成基因簇 (BGC)、天然产物、功能、机制和应用的所有知识，并概述了该蛋白超家族可能的未来研究方向。