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Genome mining of a fungal endophyte of Taxus yunnanensis (Chinese yew) leads to the discovery of a novel azaphilone polyketide, lijiquinone.
Microbial Biotechnology ( IF 5.7 ) Pub Date : 2020-04-12 , DOI: 10.1111/1751-7915.13568
Jesse W Cain 1 , Kristin I Miller 1 , John A Kalaitzis 1 , Rocky Chau 1 , Brett A Neilan 1, 2
Affiliation  

Genome mining of Ascomycete sp. F53 (F53), a fungal endophyte of the traditional Chinese medicinal plant Taxus yunnanensis (Chinese yew), revealed 35 putative specialized metabolite biosynthesis gene clusters, one of which encodes a rarely seen tandem polyketide synthase pathway with close homology to azaphilone biosynthesis pathways. A novel compound, lijiquinone 1, was subsequently isolated from F53 and structurally and functionally characterized. The m/z 385 [M + H+]+ compound, comprised of a cyclohexenone side group attached to a core bicyclic ring, displayed cytotoxicity against human myeloma cells (IC50 = 129 μM), as well as antifungal activity against Candida albicans (IC50 = 79 μM) and Cryptococcus albidus (IC50 = 141 μM). Our results suggest that enzymes encoded on the lij gene cluster are responsible for the synthesis of 1 and that the medicinal properties of T. yunnanensis could be partially mediated by this novel azaphilone. This study highlights the utility of combining traditional knowledge with contemporary genomic approaches for the discovery of new bioactive compounds.

中文翻译:

云南红豆杉真菌内生菌的基因组挖掘导致发现一种新型的氮杂苯氮酮聚酮化合物利吉醌。

Ascomycete sp。的基因组采矿。F53(F53)是传统中草药云南红豆杉的真菌内生菌,揭示了35个推定的专门代谢产物生物合成基因簇,其中一个编码罕见的串联聚酮化合物合酶途径,与氮杂磷酮生物合成途径具有高度同源性。随后从F53中分离出新型化合物lijiquinone 1,并对其结构和功能进行了表征。该M / Z 385 [M + H + ] +化合物,包括连接到核心双环的环己烯酮侧基,对人骨髓瘤细胞的细胞毒性中显示的(IC 50 = 129μM)以及对白色念珠菌(IC 50  = 79μM)和白色隐球菌(IC 50  = 141μM)的抗真菌活性。我们的结果表明,lij基因簇上编码的酶负责1的合成,而云南山毛榉的药用特性可能部分地由这种新型氮杂苯甲酮介导。这项研究强调了将传统知识与现代基因组学方法相结合以发现新的生物活性化合物的实用性。
更新日期:2020-04-12
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