Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans
Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans
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DOI：
10.1038/nchembio869
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发表时间：
2007-04-01
影响因子：
14.8
通讯作者：
Hertweck, Christian
中科院分区：
文献类型：
--
作者：
Bergmann, Sebastian;Schuemann, Julia;Hertweck, Christian
在后基因组时代，越来越明显的是，在标准发酵条件下观察到的代谢谱并不能反映微生物的大量预测生物合成基因。在没有特定（在大多数情况下未知）触发这些基因位点保持沉默。由于这些隐藏基因簇可能编码重要毒力因子、毒素或甚至候选药物的生物合成，因此迫切需要激活它们的新策略以利用这种基本上未开发的潜在生物活性化合物库（1，2）。通过基因组挖掘发现新的微生物代谢产物已被证明是一种非常有前途的方法3-15。即便如此，沉默基因簇的研究仍然是一个巨大的挑战，特别是在真菌中（16）。在这里，我们报告了一种新的策略，成功地诱导沉默的代谢途径的重要模式生物构巢曲霉，这导致了新的PKS-NRPS杂合代谢产物的发现。
In the postgenomic era it has become increasingly apparent that the vast number of predicted biosynthesis genes of microorganisms is not reflected by the metabolic profile observed under standard fermentation conditions. In the absence of a particular (in most cases unknown) trigger these gene loci remain silent. Because these cryptic gene clusters may code for the biosynthesis of important virulence factors, toxins, or even drug candidates, new strategies for their activation are urgently needed to make use of this largely untapped reservoir of potentially bioactive compounds(1,2). The discovery of new microbial metabolites through genome mining has proven to be a very promising approach 3-15. Even so, the investigation of silent gene clusters is still a substantial challenge, particularly in fungi(16). Here we report a new strategy for the successful induction of a silent metabolic pathway in the important model organism Aspergillus nidulans, which led to the discovery of novel PKS-NRPS hybrid metabolites.