Sphingolipids are produced by nearly all eukaryotes where they play significant roles in cellular processes such as cell growth, division, programmed cell death, angiogenesis, and inflammation. While it was previously believed that sphingolipids were quite rare among bacteria, bioinformatic analysis of the recently identified bacterial sphingolipid synthesis genes suggests that these lipids are likely to be produced by a wide range of microbial species. The sphingolipid synthesis pathway consists of three critical enzymes. Serine palmitoyltransferase catalyzes the condensation of serine with palmitoyl-CoA (or palmitoyl-acyl carrier protein), ceramide synthase adds the second acyl chain, and a reductase reduces the ketone present on the long-chain base. While there is general agreement regarding the identity of these bacterial enzymes, the precise mechanism and order of chemical reactions for microbial sphingolipid synthesis is more ambiguous. Two mechanisms have been proposed. First, the synthesis pathway may follow the well characterized eukaryotic pathway in which the long-chain base is reduced prior to the addition of the second acyl chain. Alternatively, our previous work suggests that addition of the second acyl chain precedes the reduction of the long-chain base. To distinguish between these two models, we investigated the subcellular localization of these three key enzymes. We found that serine palmitoyltransferase and ceramide synthase are localized to the cytoplasm, whereas the ceramide reductase is in the periplasmic space. This is consistent with our previously proposed model wherein the second acyl chain is added in the cytoplasm prior to export to the periplasm where the lipid molecule is reduced.

中文翻译：

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细菌鞘脂合成酶的空间组织

鞘脂几乎由所有真核生物产生，在细胞生长、分裂、程序性细胞死亡、血管生成和炎症等细胞过程中发挥重要作用。虽然以前认为鞘脂在细菌中相当罕见，但最近发现的细菌鞘脂合成基因的生物信息学分析表明，这些脂质可能是由多种微生物物种产生的。鞘脂合成途径由三种关键酶组成。丝氨酸棕榈酰转移酶催化丝氨酸与棕榈酰辅酶A（或棕榈酰酰基载体蛋白）的缩合，神经酰胺合酶添加第二个酰基链，还原酶还原长链碱基上存在的酮。虽然人们对这些细菌酶的身份达成了普遍共识，但微生物鞘脂合成的化学反应的精确机制和顺序却更加模糊。已经提出了两种机制。首先，合成途径可以遵循充分表征的真核途径，其中长链碱基在添加第二酰基链之前被还原。或者，我们之前的工作表明，在长链碱基的还原之前添加第二个酰基链。为了区分这两种模型，我们研究了这三种关键酶的亚细胞定位。我们发现丝氨酸棕榈酰转移酶和神经酰胺合酶位于细胞质，而神经酰胺还原酶位于周质空间。这与我们之前提出的模型一致，其中第二酰基链在输出到脂质分子被还原的周质之前添加到细胞质中。