Induced Production, Synthesis, and Immunomodulatory Action of Clostrisulfone, a Diarylsulfone from Clostridium acetobutylicum.
Induced Production, Synthesis, and Immunomodulatory Action of Clostrisulfone, a Diarylsulfone from Clostridium acetobutylicum.
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DOI：
10.1002/chem.202003500
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Hertweck C
中科院分区：
文献类型：
--
作者：
Neuwirth T;Letzel AC;Tank C;Ishida K;Cyrulies M;Schmölz L;Lorkowski S;Hertweck C
厌氧菌乙酰丁酸梭菌属于最重要的工业用菌。虽然基因组挖掘表明乙酰丁酸杆菌具有很高的次生代谢潜力，但大多数生物合成基因簇的功能是隐蔽的。我们报道，添加超生理浓度的半胱氨酸引发了一种新的天然产物--闭链舒酮的形成(1)。其结构经核磁共振、质谱学和参比化合物的化学合成确证。克罗斯特利酮是第一个报道的含有二苯基砜支架的天然产品。一项仿生合成表明，五甲基色满酚衍生的自由基可以捕获二氧化硫形成1。在以细胞为基础的小鼠巨噬细胞实验中，观察到在1的存在下，脂多糖诱导的一氧化氮释放的两相和剂量依赖的调节。工业厌氧菌乙酰丁酸梭菌用半胱氨酸诱导，发现了一种史无前例的二芳基磺酸天然产物，名为CLS，这可能是由于铬衍生自由基捕获二氧化硫所致。其结构经核磁共振确证，并经合成得到确证。生育酚相关分子发挥免疫调节作用(见图)。
The anaerobe Clostridium acetobutylicum belongs to the most important industrially used bacteria. Whereas genome mining points to a high potential for secondary metabolism in C. acetobutylicum, the functions of most biosynthetic gene clusters are cryptic. We report that the addition of supra‐physiological concentrations of cysteine triggered the formation of a novel natural product, clostrisulfone (1). Its structure was fully elucidated by NMR, MS and the chemical synthesis of a reference compound. Clostrisulfone is the first reported natural product with a diphenylsulfone scaffold. A biomimetic synthesis suggests that pentamethylchromanol‐derived radicals capture sulfur dioxide to form 1. In a cell‐based assay using murine macrophages a biphasic and dose‐dependent regulation of the LPS‐induced release of nitric oxide was observed in the presence of 1. Induction of the industrial anaerobe Clostridium acetobutylicum with cysteine led to the discovery of an unprecedented diarylsulfone natural product named clostrisulfone that likely results from sulfur dioxide capture by chromane‐derived radicals. Its structure was elucidated by NMR and confirmed by synthesis. The tocopherol‐related molecule exerts immunomodulatory activities (see figure).
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影响因子：
16.6
作者：
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通讯作者：
Hertweck, Christian
影响因子：
16.6
作者：
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2.7
作者：
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影响因子：
5.2
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影响因子：
4.2
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通讯作者：
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