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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Aspernidine A and B, prenylated isoindolinone alkaloids from the model fungus Aspergillus nidulans
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Aspernidine A and B, prenylated isoindolinone alkaloids from the model fungus Aspergillus nidulans

机译：天冬氨酸A和B，来自模型真菌Aspergillus nidulans的烯丙基异吲哚啉酮生物碱

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摘要

Filamentous fungi produce a multitude of bioactive natural products, which cover a broad range of useful pharmaceutical activities. Many of these compounds were discovered by traditional natural product screening approaches and have found various applications in modern medicine. Through recent whole-genome sequencing projects, however, we become increasingly aware that the biosynthetic potential of microorganisms is much higher than expected. In many cases, the number of putative biosynthetic genes of fungi and bacteria is not reflected by the metabolic profile observed under laboratory culture conditions. Several gene loci encoding diverse metabolic pathways seem to lack expression in the absence of particular physical or chemical stimuli. Mining the genome of Aspergillus nidulans for putative biosynthesis gene clusters revealed biosynthetic abilities for the production of up to 28 polyketides and 24 nonribosomally synthesized peptides. However, this abundance of gene clusters clearly outnumbers the known secondary metabolites of this fungus. To gain access to this untapped reservoir of potentially bioactive natural products, various strategies to induce the expression of silent genes have been developed. Important recent examples involve the ectopic expression of a regulatory gene, the induction of a transcription activator by promotor exchange, as well as modulation of the epigenetic regulation of biosynthetic genes at the chromatin level.
机译：丝状真菌产生多种具有生物活性的天然产物，这些产物涵盖了广泛的有用药物活性。这些化合物中的许多是通过传统的天然产物筛选方法发现的，并已在现代医学中发现了多种应用。然而，通过最近的全基因组测序项目，我们越来越意识到微生物的生物合成潜力远高于预期。在许多情况下，在实验室培养条件下观察到的代谢谱未反映出真菌和细菌的假定生物合成基因的数量。在没有特定物理或化学刺激的情况下，编码多种代谢途径的几种基因座似乎缺乏表达。挖掘构巢曲霉的基因组以用于推测的生物合成基因簇，揭示了产生多达28个聚酮化合物和24个非核糖体合成肽的生物合成能力。但是，这种丰富的基因簇明显超过了这种真菌的已知次生代谢产物。为了获得可能具有生物活性的天然产物的尚未开发的储库，已经开发了多种诱导沉默基因表达的策略。最近的重要例子涉及调节基因的异位表达，通过启动子交换诱导转录激活子，以及在染色质水平上调节生物合成基因的表观遗传调控。

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