Abstract 1349: Convergent evolution of bacterial ceramide synthesis
Abstract 1349: Convergent evolution of bacterial ceramide synthesis
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摘要 1349：细菌神经酰胺合成的趋同进化
DOI：
10.1016/j.jbc.2023.103790
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发表时间：
2023
影响因子：
4.8
通讯作者：
Klein E
中科院分区：
文献类型：
--
作者：
Klein E
细菌合成具有多种生理功能的鞘脂。尽管它们在介导宿主炎症、细胞分化和保护免受环境应激中起作用，但它们的生物合成途径仍然不确定，因为几种必需的真核神经酰胺合成酶没有细菌同源物。利用遗传和生物化学方法，我们确定了细菌神经酰胺合成的完整途径。生物信息学和系统发育分析揭示了这些基因在广泛的细菌分类群中的存在，并导致我们发现了第一个产生神经酰胺的革兰氏阳性菌种。纯化蛋白质的生化实验支持一种模型，其中细菌途径以不同于真核生物的顺序运作。此外，系统发育分析与细菌和真核神经酰胺途径的独立进化一致。目前正在进行的工作是阐明合成酶的特异性亚细胞定位，并鉴定将鞘脂转运至革兰氏阴性菌外膜所需的其他蛋白质。
Bacteria synthesize numerous types of sphingolipids with various physiological functions. Despite their roles in mediating host inflammation, cellular differentiation, and protection from environmental stress, their biosynthetic pathway remains undefined since several essential eukaryotic ceramide synthesis enzymes have no bacterial homologue. Using genetic and biochemical approaches, we identified the complete pathway for bacterial ceramide synthesis. Bioinformatic and phylogenetic analyses revealed the presence of these genes in a broad range of bacterial taxa and led to our discovery of the first Gram‐positive species to produce ceramides. Biochemical experiments with purified proteins support a model in which the bacterial pathway operates in a different order than in eukaryotes. Furthermore, phylogenetic analyses are consistent with the independent evolution of the bacterial and eukaryotic ceramide pathways. Current work is being done to elucidate the specific subcellular localization of the synthetic enzymes and identify additional proteins required for the transport of sphingolipids to the outer membrane of Gram‐negative bacteria.