Ernst Dustin C, Downs Diana M
Department of Microbiology, University of Georgia, Athens, Georgia, USA.
Department of Microbiology, University of Georgia, Athens, Georgia, USA
J Bacteriol. 2015 Apr;197(8):1368-77. doi: 10.1128/JB.02506-14. Epub 2015 Feb 2.
Coenzyme A (CoA) is a ubiquitous coenzyme involved in fundamental metabolic processes. CoA is synthesized from pantothenic acid by a pathway that is largely conserved among bacteria and eukaryotes and consists of five enzymatic steps. While higher organisms, including humans, must scavenge pantothenate from the environment, most bacteria and plants are capable of de novo pantothenate biosynthesis. In Salmonella enterica, precursors to pantothenate can be salvaged, but subsequent intermediates are not transported due to their phosphorylated state, and thus the pathway from pantothenate to CoA is considered essential. Genetic analyses identified the STM4195 gene product of Salmonella enterica serovar Typhimurium as a transporter of pantothenate precursors, ketopantoate and pantoate and, to a lesser extent, pantothenate. Further results indicated that STM4195 transports a product of CoA degradation that serves as a precursor to CoA and enters the biosynthetic pathway between PanC and CoaBC (dfp). The relevant CoA derivative is distinguishable from pantothenate, pantetheine, and pantethine and has spectral properties indicating the adenine moiety of CoA is intact. Taken together, the results presented here provide evidence of a transport mechanism for the uptake of ketopantoate, pantoate, and pantothenate and demonstrate a role for STM4195 in the salvage of a CoA derivative of unknown structure. The STM4195 gene is renamed panS to reflect participation in pantothenate salvage that was uncovered herein.
This manuscript describes a transporter for two pantothenate precursors in addition to the existence and transport of a salvageable coenzyme A (CoA) derivative. Specifically, these studies defined a function for an STM protein in S. enterica that was distinct from the annotated role and led to its designation as PanS (pantothenate salvage). The presence of a salvageable CoA derivative and a transporter for it suggests the possibility that this compound is present in the environment and may serve a role in CoA synthesis for some organisms. As such, this work raises important question about CoA salvage that can be pursued with future studies in bacteria and other organisms.
辅酶A（CoA）是一种参与基本代谢过程的普遍存在的辅酶。CoA由泛酸通过一条在细菌和真核生物中基本保守的途径合成，该途径由五个酶促步骤组成。虽然包括人类在内的高等生物必须从环境中摄取泛酸盐，但大多数细菌和植物能够从头合成泛酸盐。在肠炎沙门氏菌中，泛酸盐的前体可以被挽救，但随后的中间体由于其磷酸化状态而无法运输，因此从泛酸盐到CoA的途径被认为是必不可少的。遗传分析确定肠炎沙门氏菌血清型鼠伤寒沙门氏菌的STM4195基因产物是泛酸盐前体、α-酮泛解酸和泛解酸的转运蛋白，在较小程度上也是泛酸盐的转运蛋白。进一步的结果表明，STM4195转运一种CoA降解产物，该产物作为CoA的前体并进入PanC和CoaBC（dfp）之间的生物合成途径。相关的CoA衍生物与泛酸盐、泛硫乙胺和泛酰巯基乙胺不同，并且具有表明CoA的腺嘌呤部分完整的光谱特性。综上所述，本文给出的结果为α-酮泛解酸、泛解酸和泛酸盐的摄取提供了一种转运机制的证据，并证明了STM4195在挽救一种结构未知的CoA衍生物中的作用。STM4195基因重新命名为panS，以反映本文中发现的其参与泛酸盐挽救的作用。
本手稿描述了一种除了可挽救的辅酶A（CoA）衍生物的存在和转运之外的两种泛酸盐前体的转运蛋白。具体而言，这些研究确定了肠炎沙门氏菌中一种STM蛋白的功能，该功能与注释的作用不同，并导致其被命名为PanS（泛酸盐挽救）。一种可挽救的CoA衍生物及其转运蛋白的存在表明这种化合物可能存在于环境中，并可能在某些生物体的CoA合成中发挥作用。因此，这项工作提出了关于CoA挽救的重要问题，可在未来对细菌和其他生物体的研究中进行探讨。
