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首页> 外文期刊>Applied Microbiology and Biotechnology >Rational design for heterologous production of aurovertin-type compounds in Aspergillus nidulans
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Rational design for heterologous production of aurovertin-type compounds in Aspergillus nidulans

机译：Aspergillus Nidulans的抗植物型化合物的合理设计

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摘要

Aurovertins are the structurally diverse polyketides that distribute widely in different fungal species. They feature a 2,6-dioxabicyclo[3.2.1]-octane ring in structure and exhibit the potential antitumor activity against breast cancer as F1-ATPase beta subunit inhibitor. In this study, we constructed the biosynthetic pathway of aurovertin in an Aspergillus nidulans host and obtained seven aurovertin-type compounds. Surprisingly, three new aurovertin geometric isomers were characterized. By introducing an inducible promoter xylP(p) in the pathway gene acyltransferase aurG, we can control the product ratios among different aurovertin compounds by adding glucose and/or inducer xylose. The yields of aurovertins could be increased up to about 20 times by adding a constitutive promoter gpdA(p) to transcription factor AurF, which indicates AurF's positive role in the biosynthesis of aurovertin. Taken together, our results provided not only an efficient way to generate bioactive fungal natural products but also realized the rational controlling their yields with designed promoters.
机译：Aurovertins是在不同的真菌物种中广泛分布的结构多样化的聚酮基。它们具有2,6-二恶英（3.2.1） - 辛烷环结构，并表现出对乳腺癌的潜在抗肿瘤活性作为F1-ATPaseβ亚基抑制剂。在这项研究中，我们在Aspergillus Nidulans宿主中构建了Aurovertin的生物合成途径，并获得了七种Aurovertin型化合物。令人惊讶的是，表征了三种新的Aurovertin几何异构体。通过在途径基因酰基转移酶AURG中引入诱导型启动子Xylp（P），我们可以通过添加葡萄糖和/或诱导型木糖来控制不同AUROVERTIN化合物中的产品比。通过将组成型启动子GPDA（P）加入转录因子AURF，可以增加菌射素的产率高达约20次，这表明AURF在Aurovertin的生物合成中的积极作用。我们的结果不仅提供了产生生物活性真菌天然产品的有效方法，还提供了对设计启动子的理性控制其产量。

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