Immunosuppressive Polyketides from Mantis-Associated Daldinia eschscholzii
Immunosuppressive Polyketides from Mantis-Associated Daldinia eschscholzii
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来自螳螂相关 Daldinia eschscholzii 的免疫抑制聚酮化合物
DOI：
10.1021/ja110932p
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发表时间：
2011-04-20
影响因子：
15
通讯作者：
Tan, Ren X.
中科院分区：
文献类型：
--
作者：
Zhang, Ying L.;Zhang, Jie;Tan, Ren X.
具有未知结构的聚酮化合物对于发现新药物和农用化学品是高度期望的。在这里，螳螂相关的Daldinia eschscholzii，一种已知产生免疫抑制剂dalesconols A和B的真菌，被发现同时产生四种新的骨架，能够形成真菌聚酮化合物的不寻常的化学物质，其中七种结构独特，具有显著的免疫抑制作用。特别是，微生物的放大发酵使得能够对次要或“过渡”中间体聚酮化合物进行结构表征，从而能够合理地识别分别由四个、五个、六个和八个乙酸酯单元的缩合引发的四种生物合成途径。此外，三酮的脱羰基反应，如在daeschol A的情况下，除了孢子素C和nodulone的结构校正外，首次被描述。这项工作提供了一组新的免疫抑制分子，对药物发现具有重要意义。
Polyketides with unknown architectures are highly desired for the discovery of new drugs and agrochemicals. Here, the mantis-associated Daldinia eschscholzii, a fungus known to produce immunosuppressants dalesconols A and B, was found to simultaneously generate four novel skeletons capable of shaping the unusual chemistry of the fungal polyketides, of which seven were structurally unique and substantially immunosuppressive. In particular, the scaled-up fermentation of the microbe enabled the structural characterization of minor or "transitional" intermediate polyketides that allowed the reasonable recognition of the four biosynthetic pathways initiated by condensations of four, five, six and eight acetate units, respectively. Furthermore, the decarbonylation reaction of triketone, as in the case of daeschol A, was described for the first time, in addition to the structural correction of sporothrin C and nodulone. The work provided a set of novel immunosuppressive molecules that are of significance to drug discovery.