Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host-pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1--a previously identified human candidate gene--is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans.

中文翻译：

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CASD1通过共价乙酰酶中间体催化唾液酸的9-O-乙酰化。

唾液酸是糖蛋白和糖脂的末端糖，在发育，细胞识别过程和宿主-病原体相互作用中起着重要作用。唾液酸的常见修饰是9-O-乙酰化，这与唾液酸糖识别，神经节苷脂生物学以及急性淋巴细胞白血病细胞的存活和耐药性有关。尽管有许多功能含义，但到目前为止，9-O-乙酰化的分子基础仍然难以捉摸。遵循细胞方法，包括通过CRISPR / Cas基因组编辑进行选择性基因敲除，我们在这里显示CASD1（一种先前鉴定的人类候选基因）对于唾液酸9-O-乙酰化至关重要。用CASD1纯化的N末端腔结构域进行的体外分析表明，乙酰基从乙酰辅酶A转移至CMP活化的唾液酸，并形成了共价乙酰酶中间体。我们的研究提供了直接的证据，表明CASD1是唾液酸O-乙酰基转移酶，并且是9-O-乙酰化唾液聚糖生物合成中的关键酶。