Institute for Chemistry and Biology of the, Marine Environment (ICBM), Organic Geochemistry, Carl von Ossietzky University Oldenburg, 26129, Oldenburg, Germany.
Institute for Chemistry and Biology of the, Marine Environment (ICBM), Marine Geochemistry, Carl von Ossietzky University Oldenburg, 26129, Oldenburg, Germany.
Chembiochem. 2023 Jan 17;24(2):e202200584. doi: 10.1002/cbic.202200584. Epub 2022 Dec 8.
Coenzyme A (CoA) thioesters are formed during anabolic and catabolic reactions in every organism. Degradation pathways of growth-supporting substrates in bacteria can be predicted by differential proteogenomic studies. Direct detection of proposed metabolites such as CoA thioesters by high-performance liquid chromatography coupled with high-resolution mass spectrometry can confirm the reaction sequence and demonstrate the activity of these degradation pathways. In the metabolomes of the anaerobic sulfate-reducing bacterium Desulfobacula toluolica Tol2 grown with different substrates various CoA thioesters, derived from amino acid, fatty acid or alcohol metabolism, have been detected. Additionally, the cell extracts of this bacterium revealed a number of CoA analogues with molecular masses increased by 1 dalton. By comparing the chromatographic and mass spectrometric properties of synthetic reference standards with those of compounds detected in cell extracts of D. toluolica Tol2 and by performing co-injection experiments, these analogues were identified as inosino-CoAs. These CoA thioesters contain inosine instead of adenosine as the nucleoside. To the best of our knowledge, this finding represents the first detection of naturally occurring inosino-CoA analogues.
辅酶 A (CoA) 硫酯在每个生物体的合成代谢和分解代谢反应中形成。通过差异蛋白基因组学研究可以预测支持生长的底物的降解途径。通过高效液相色谱与高分辨率质谱联用直接检测 CoA 硫酯等拟议代谢物，可以证实反应序列并证明这些降解途径的活性。在不同底物培养的厌氧硫酸盐还原菌脱硫杆菌（Desulfobacula toluolica Tol2）的代谢组中，已检测到来自氨基酸、脂肪酸或醇代谢的各种 CoA 硫酯。此外，该细菌的细胞提取物中还揭示了许多分子量增加 1 道尔顿的 CoA 类似物。通过将合成标准品的色谱和质谱特性与在 D. toluolica Tol2 细胞提取物中检测到的化合物进行比较，并进行共注射实验，这些类似物被鉴定为肌苷酰-CoA。这些 CoA 硫酯含有肌苷而不是腺嘌呤作为核苷。据我们所知，这一发现代表了对天然存在的肌苷酰-CoA 类似物的首次检测。
