Pederin-Type Pathways of Uncultivated Bacterial Symbionts: Analysis ofO-Methyltransferases and Generation of a Biosynthetic Hybrid,Journal of the American Chemical Society

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Pederin-Type Pathways of Uncultivated Bacterial Symbionts: Analysis ofO-Methyltransferases and Generation of a Biosynthetic Hybrid
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2009-03-04 , DOI: 10.1021/ja808889k
Katrin Zimmermann ₁ , Marianne Engeser ₁ , John W. Blunt ₁ , Murray H. G. Munro ₁ , Jörn Piel ₁

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The complex polyketide pederin is a potent antitumor agent isolated from Paederus spp. rove beetles. We have previously isolated a set of genes from a bacterial endosymbiont that are good candidates for pederin biosynthesis. To biochemically study this pathway, we expressed three methyltransferases from the putative pederin pathway and used the partially unmethylated analogue mycalamide A from the marine sponge Mycale hentscheli as test substrate. Analysis by high-resolution MS/MS and NMR revealed that PedO regiospecifically methylates the marine compound to generate the nonnatural hybrid compound 18-O-methylmycalamide A with increased cytotoxicity. To our knowledge, this is the first biochemical evidence that invertebrates can obtain defensive complex polyketides from bacterial symbionts.

中文翻译：

未培养细菌共生体的 Pederin 型途径：O-甲基转移酶的分析和生物合成杂种的产生

复合聚酮化合物 pederin 是一种从 Paederus spp 中分离出来的强效抗肿瘤剂。罗夫甲虫。我们之前已经从细菌内共生体中分离出一组基因，这些基因是 pederin 生物合成的良好候选者。为了对这条通路进行生化研究，我们表达了来自推定的 pederin 通路的三种甲基转移酶，并使用来自海洋海绵 Mycale hentscheli 的部分未甲基化类似物 mycalamide A 作为测试底物。高分辨率 MS/MS 和 NMR 分析表明，PedO 区域特异性地甲基化海洋化合物以生成具有增加细胞毒性的非天然杂合化合物 18-O-甲基霉酰胺 A。据我们所知，这是无脊椎动物可以从细菌共生体中获得防御性复合聚酮化合物的第一个生化证据。

更新日期：2009-03-04

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