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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei.
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Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei.

机译：海洋海绵Theonella swinhoei的未经培养的细菌共生体可合成抗肿瘤聚酮化合物。

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摘要

Bacterial symbionts have long been suspected to be the true producers of many drug candidates isolated from marine invertebrates. Sponges, the most important marine source of biologically active natural products, have been frequently hypothesized to contain compounds of bacterial origin. This symbiont hypothesis, however, remained unproven because of a general inability to cultivate the suspected producers. However, we have recently identified an uncultured Pseudomonas sp. symbiont as the most likely producer of the defensive antitumor polyketide pederin in Paederus fuscipes beetles by cloning the putative biosynthesis genes. Here we report closely related genes isolated from the highly complex metagenome of the marine sponge Theonella swinhoei, which is the source of the onnamides and theopederins, a group of polyketides that structurally resemble pederin. Sequence features of the isolated genes clearly indicate that it belongs to a prokaryotic genome and should be responsible for the biosynthesis of almost the entire portion of the polyketide structure that is correlated with antitumor activity. Besides providing further proof for the role of the related beetle symbiont-derived genes, these findings raise intriguing ecological and evolutionary questions and have important general implications for the sustainable production of otherwise inaccessible marine drugs by using biotechnological strategies.
机译：长期以来，人们一直怀疑细菌共生体是从海洋无脊椎动物中分离出来的许多候选药物的真正生产者。海绵是生物活性天然产物的最重要的海洋来源，经常被认为含有细菌来源的化合物。然而，由于普遍无法培养可疑的生产者，因此这种共生论的假设尚未得到证实。但是，我们最近发现了未经培养的假单胞菌。通过克隆假定的生物合成基因，共生菌是在Paederus fuscipes甲虫中最有可能产生防御性抗肿瘤聚酮pederin的物质。在这里，我们报告了从海洋海绵Theonella swinhoei的高度复杂的基因组中分离的密切相关的基因，Theonella swinhoei是onnamides和theopederin的来源，后者是一组类似于pederin的聚酮。分离的基因的序列特征清楚地表明它属于原核基因组，应该负责与抗肿瘤活性相关的聚酮化合物结构的几乎整个部分的生物合成。除了为相关的甲虫共生体相关基因的作用提供进一步的证据外，这些发现还提出了有趣的生态和进化问题，并且对使用生物技术策略可持续生产否则无法获得的海洋药物具有重要的一般意义。

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