Transcriptomic and metabolomic profiling of ionic liquid stimuli unveils enhanced secondary metabolism in Aspergillus nidulans.
Transcriptomic and metabolomic profiling of ionic liquid stimuli unveils enhanced secondary metabolism in Aspergillus nidulans.
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DOI：
10.1186/s12864-016-2577-6
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发表时间：
2016-04-12
期刊：
影响因子：
4.4
通讯作者：
Silva Pereira C
中科院分区：
文献类型：
--
作者：
Alves PC;Hartmann DO;Núñez O;Martins I;Gomes TL;Garcia H;Galceran MT;Hampson R;Becker JD;Silva Pereira C
在标准的实验室培养条件下，丝状真菌，特别是子囊菌门，产生多种生物活性代谢物的内在潜力在很大程度上保持沉默。已经描述了无数的策略来触发它们的产生，最简单的一种是操纵生长培养基的组成。补充离子液体的培养基出人意料地增强了青霉菌产生的细胞外代谢物的多样性。这一发现促使我们评估离子液体刺激对中性曲霉真菌代谢的影响及其对次生代谢物（SMs）生物合成的影响。全转录谱分析显示，暴露于0.7 M氯化胆碱或1-乙基-3-甲基咪唑氯显著影响了编码初级和次级代谢的基因的表达。两种离子液体都能诱导应激反应和解毒机制，但对每种刺激的反应谱是独特的。胆碱上调初级代谢，1-乙基-3-甲基咪唑下调初级代谢；两者都刺激了乙酰辅酶a（许多SMs的关键前体）和非蛋白质氨基酸（生物活性SMs的组成部分）的产生。总共，66个描述的骨干基因中有21个发生了上调。因此，真菌代谢组的差异分析表明，与对照条件相比，添加离子液体的生长培养基导致了大约40个不同的离子质量累积。特别地，它刺激了单双苯酮和奥塞林酸的产生，否则就会产生隐藏物。编码相应聚酮生物合成酶的基因（即骨干基因）表达量较对照增加。在离体全组织实验（Thelial Live Targeted epithelial; theelite™）中，相应的代谢物提取物显示出增加的细胞极性调节电位。离子液体是一种完全由离子组成的多种化学物质，可以为进一步解决天然化合物的多样性提供一种意想不到的手段，指导具有临床潜力的真菌代谢物的发现。本文的在线版本（doi:10.1186/s12864-016-2577-6）包含补充材料，可供授权用户使用。
The inherent potential of filamentous fungi, especially of Ascomycota, for producing diverse bioactive metabolites remains largely silent under standard laboratory culture conditions. Innumerable strategies have been described to trigger their production, one of the simplest being manipulation of the growth media composition. Supplementing media with ionic liquids surprisingly enhanced the diversity of extracellular metabolites generated by penicillia. This finding led us to evaluate the impact of ionic liquids’ stimuli on the fungal metabolism in Aspergillus nidulans and how it reflects on the biosynthesis of secondary metabolites (SMs). Whole transcriptional profiling showed that exposure to 0.7 M cholinium chloride or 1-ethyl-3-methylimidazolium chloride dramatically affected expression of genes encoding both primary and secondary metabolism. Both ionic liquids apparently induced stress responses and detoxification mechanisms but response profiles to each stimulus were unique. Primary metabolism was up-regulated by choline, but down-regulated by 1-ethyl-3-methylimidazolium chloride; both stimulated production of acetyl-CoA (key precursor to numerous SMs) and non proteinogenic amino acids (building blocks of bioactive classes of SMs). In total, twenty one of the sixty six described backbone genes underwent up-regulation. Accordingly, differential analysis of the fungal metabolome showed that supplementing growth media with ionic liquids resulted in ca. 40 differentially accumulated ion masses compared to control conditions. In particular, it stimulated production of monodictyphenone and orsellinic acid, otherwise cryptic. Expression levels of genes encoding corresponding polyketide biosynthetic enzymes (i.e. backbone genes) increased compared to control conditions. The corresponding metabolite extracts showed increased cell polarity modulation potential in an ex vivo whole tissue assay (Thelial Live Targeted Epithelia; theLiTE™). Ionic liquids, a diverse class of chemicals composed solely of ions, can provide an unexpected means to further resolve the diversity of natural compounds, guiding discovery of fungal metabolites with clinical potential. The online version of this article (doi:10.1186/s12864-016-2577-6) contains supplementary material, which is available to authorized users.