Protein myristoylation is a C14 fatty acid modification found in all living organisms. Myristoylation tags either the N-terminal alpha groups of cysteine or glycine residues through amide bonds or lysine and cysteine side chains directly or indirectly via glycerol thioester and ester linkages. Before transfer to proteins, myristate must be activated into myristoyl coenzyme A in eukaryotes or, in bacteria, to derivatives like phosphatidylethanolamine. Myristate originates through de novo biosynthesis (e.g., plants), from external uptake (e.g., human tissues), or from mixed origins (e.g., unicellular organisms). Myristate usually serves as a molecular anchor, allowing tagged proteins to be targeted to membranes and travel across endomembrane networks in eukaryotes. In this review, we describe and discuss the metabolic origins of protein-bound myristate. We review strategies for in vivo protein labeling that take advantage of click-chemistry with reactive analogs, and we discuss new approaches to the proteome-wide discovery of myristate-containing proteins. The machineries of myristoylation are described, along with how protein targets can be generated directly from translating precursors or from processed proteins. Few myristoylation catalysts are currently described, with only N-myristoyltransferase described to date in eukaryotes. Finally, we describe how viruses and bacteria hijack and exploit myristoylation for their pathogenicity.

蛋白肉豆蔻酰化是在所有生物体中发现的 C14 脂肪酸修饰。肉豆蔻酰化通过酰胺键或赖氨酸和半胱氨酸侧链直接或通过甘油硫酯和酯键间接标记半胱氨酸或甘氨酸残基的 N 端 α 基团。在转移到蛋白质之前，肉豆蔻酸酯必须在真核生物中被激活为肉豆蔻酰辅酶 A，或者在细菌中被激活为磷脂酰乙醇胺等衍生物。肉豆蔻酸通过从头生物合成（例如植物）、外部摄取（例如人体组织）或混合来源（例如，单细胞生物）。肉豆蔻酸酯通常用作分子锚，允许标记的蛋白质靶向膜并穿过真核生物的内膜网络。在这篇综述中，我们描述和讨论了蛋白质结合肉豆蔻酸酯的代谢起源。我们回顾了体内策略利用点击化学与反应性类似物的蛋白质标记，我们讨论了在蛋白质组范围内发现含有肉豆蔻酸的蛋白质的新方法。描述了肉豆蔻酰化的机制，以及如何从翻译前体或加工蛋白质中直接生成蛋白质靶标。目前描述的肉豆蔻酰化催化剂很少，迄今为止在真核生物中仅描述了 N-肉豆蔻酰转移酶。最后，我们描述了病毒和细菌如何劫持和利用肉豆蔻酰化来实现其致病性。