Polyketide assembly lines of uncultivated sponge symbionts from structure-based gene targeting
Polyketide assembly lines of uncultivated sponge symbionts from structure-based gene targeting
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DOI：
10.1038/nchembio.176
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发表时间：
2009-07-01
影响因子：
14.8
通讯作者：
Piel, Joern
中科院分区：
文献类型：
--
作者：
Fisch, Katja M.;Gurgui, Cristian;Piel, Joern
越来越多的证据表明，未培养的细菌共生体是从海绵中分离出的许多生物活性化合物的真正生产者。生物合成基因的定位和异源表达可以澄清这一问题，并为广泛的药物提供可持续的供应。然而，在通常高度复杂的共生体社区的基因识别仍然是一项具有挑战性的任务。对于聚酮化合物，海绵衍生的候选药物的最重要的群体之一，我们已经开发了一种通用的策略，允许一个快速访问基于化学部分的生物合成基因簇。使用这种方法，我们针对聚酮合酶基因从两个不同的海绵宏基因组。我们已经从海绵细菌协会获得了一个完整的途径，罕见的和有效的抗肿瘤剂Psymocinia aff。球根这些数据支持共生体假说，并提供了对以前无法获得的细菌中天然产物进化的见解。
There is increasing evidence that uncultivated bacterial symbionts are the true producers of numerous bioactive compounds isolated from marine sponges. The localization and heterologous expression of biosynthetic genes could clarify this issue and provide sustainable supplies for a wide range of pharmaceuticals. However, identification of genes in the usually highly complex symbiont communities remains a challenging task. For polyketides, one of the most important groups of sponge-derived drug candidates, we have developed a general strategy that allows one to rapidly access biosynthetic gene clusters based on chemical moieties. Using this method, we targeted polyketide synthase genes from two different sponge metagenomes. We have obtained from a sponge-bacterial association a complete pathway for the rare and potent antitumor agent psymberin from Psammocinia aff. bulbosa. The data support the symbiont hypothesis and provide insights into natural product evolution in previously inaccessible bacteria.