Unprecedented diversity of catalytic domains in the first four modules of the putative pederin polyketide synthase
Unprecedented diversity of catalytic domains in the first four modules of the putative pederin polyketide synthase
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DOI：
10.1002/cbic.200300782
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发表时间：
2004-01-03
期刊：
影响因子：
3.2
通讯作者：
Hui, DQ
中科院分区：
文献类型：
--
作者：
Piel, J;Wen, GP;Hui, DQ
菊酯类聚酮类化合物是在陆生甲虫和海洋海绵中发现的高效抗肿瘤化合物。Pederin被一般的拟蚊科和拟蚊科的甲虫用作化学防御。我们最近发现了一组推测的pederin生物合成基因，并将它们定位到一种尚未培养的假单胞菌共生体的基因组中，假单胞菌可能是真正的pederin生产者。然而，这个聚酮合成酶簇缺乏几个预期的pederin生产基因。在这里，我们报告了在共生体基因组的一个单独区域编码的额外的聚酮合成酶。它包含至少三个新的催化结构域，预计这些结构域参与了pederin链的起始和不寻常的外亚甲基键的形成。该区域被迁移性假基因所包围；这表明基因转位导致了集群组织的脱节。通过这项工作，所有可能的pederin基因都已被确定。它们在可培养细菌中的异源表达将为如何创建无脊椎动物衍生候选药物的可持续来源提供重要见解。
Polyketides of the pederin group are highly potent antitumor compounds found in terrestrial beetles and marine sponges. Pederin is used by beetles of the general Paederus and Paederidus as a chemical defense. We have recently identified a group of putative pederin biosynthesis genes and localized them to the genome of an as yet unculturable Pseudomonas sp. symbiont, the likely true pederin producer. However, this polyketide synthase cluster lacks several genes expected for pederin production. Here we report additional polyketide synthase encoded on a separate region of the symbiont genome. It contains at least three novel catalytic domains that are predicted to be involved in pederin chain initiation and the formation of an unusual exomethylene bond. The region is bordered by mobility pseudogenes; this suggests that gene transposition led to the disjointed cluster organization. With this work, all putative pederin genes have been identified. Their heterologous expression in a culturable bacterium will provide important insights into how sustainable sources of invertebrate-derived drug candidates can be created.