Department of Chemical Engineering and Biotechnology, University of Applied Sciences Darmstadt, Stephanstrasse 7, 64295, Darmstadt, Germany.
Institute for Biochemistry, Department Synthetic and Structural Biochemistry, University of Greifswald, Felix-Hausdorff-Str. 4, 17487, Greifswald, Germany.
Adv Biol (Weinh). 2021 Dec;5(12):e2100926. doi: 10.1002/adbi.202100926. Epub 2021 Oct 28.
Lysine acylation is a ubiquitous protein modification that controls various aspects of protein function, such as the activity, localization, and stability of enzymes. Mass spectrometric identification of lysine acylations has witnessed tremendous improvements in sensitivity over the last decade, facilitating the discovery of thousands of lysine acylation sites in proteins involved in all essential cellular functions across organisms of all domains of life. However, the vast majority of currently known acylation sites are of unknown function. Semi-synthetic methods for installing lysine derivatives are ideally suited for in vitro experiments, while genetic code expansion (GCE) allows the installation and study of such lysine modifications, especially their dynamic properties, in vivo. An overview of the current state of the art is provided, and its potential is illustrated with case studies from recent literature. These include the application of engineered enzymes and GCE to install lysine modifications or photoactivatable crosslinker amino acids. Their use in the context of central metabolism, bacterial and viral pathogenicity, the cytoskeleton and chromatin dynamics, is investigated.
赖氨酸酰化是一种普遍存在的蛋白质修饰，控制着蛋白质功能的各个方面，如酶的活性、定位和稳定性。在过去十年中，质谱法鉴定赖氨酸酰化的灵敏度有了显著提高，促进了在所有生命领域的生物体中参与所有基本细胞功能的蛋白质中数千个赖氨酸酰化位点的发现。然而，目前已知的绝大多数酰化位点的功能仍然未知。用于安装赖氨酸衍生物的半合成方法非常适合体外实验，而遗传密码扩展 (GCE) 则允许在体内安装和研究这种赖氨酸修饰，特别是其动态特性。本文提供了该领域的最新进展概述，并通过来自近期文献的案例研究说明了其潜力。这些包括工程酶和 GCE 的应用，以安装赖氨酸修饰或光活化交联氨基酸。研究了它们在中心代谢、细菌和病毒致病性、细胞骨架和染色质动力学中的应用。
