Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States.
Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
ACS Chem Biol. 2022 May 20;17(5):1197-1206. doi: 10.1021/acschembio.2c00141. Epub 2022 Apr 27.
Sulfonolipids (SoLs) are a unique class of sphingolipids featuring a sulfonate group compared to other sphingolipids. However, the biological functions and biosynthesis of SoLs in human microbiota have been poorly understood. Here, we report the discovery and isolation of SoLs from a human opportunistic pathogen DSM16776. We show for the first time the pro-inflammatory activity of SoLs with mice primary macrophages. Furthermore, we used both in vivo heterologous expression and in vitro biochemical reconstitution to characterize two enzymes, cysteate synthase and cysteate fatty acyltransferase, that are specifically involved in the biosynthesis of SoLs rather than other sphingolipids. Based on these two SoL-specific enzymes, our bioinformatics analysis showed a wider distribution of SoL biosynthetic genes in microbes that had not been reported as SoL producers. We selected four of these strains and verified their cysteate synthase and cysteate fatty acyltransferase activities in SoL biosynthesis. Considering this wider distribution of SoL-specific biosynthetic enzymes in the context of SoLs' activity in mediating inflammation, a common and fundamental biological process, it may suggest a more comprehensive function of SoLs at play.
磺基脂类（SoLs）是一类独特的鞘脂类，与其他鞘脂类相比，其特征是含有磺酸基。然而，人类微生物群中 SoLs 的生物学功能和生物合成仍知之甚少。在这里，我们报告了从人类机会性病原体 DSM16776 中发现和分离磺基脂类的情况。我们首次展示了 SoLs 对小鼠原代巨噬细胞的促炎活性。此外，我们使用体内异源表达和体外生化重组来表征两种酶，半胱氨酸合酶和半胱氨酸脂肪酰基转移酶，它们专门参与 SoLs 的生物合成，而不是其他鞘脂类。基于这两种 SoL 特异性酶，我们的生物信息学分析显示，SoL 生物合成基因在尚未报道为 SoL 产生菌的微生物中的分布更广。我们选择了其中的 4 株，并验证了它们在 SoL 生物合成中半胱氨酸合酶和半胱氨酸脂肪酰基转移酶的活性。考虑到 SoL 特异性生物合成酶在介导炎症这一常见和基本的生物学过程中的广泛分布，这可能表明 SoLs 发挥着更全面的功能。
