Chemical-epigenetic method to enhance the chemodiversity of the marine algicolous fungus, Aspergillus terreus OUCMDZ-2739
Chemical-epigenetic method to enhance the chemodiversity of the marine algicolous fungus, Aspergillus terreus OUCMDZ-2739
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化学表观遗传学方法增强海洋藻类真菌土曲霉 OUCMDZ-2739 的化学多样性
DOI：
10.1016/j.tet.2017.11.039
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发表时间：
2018-01-04
期刊：
影响因子：
2.1
通讯作者：
Zhu, Weiming
中科院分区：
文献类型：
--
作者：
Sun, Kunlai;Zhu, Guoliang;Zhu, Weiming
四种新的类萜被鉴定为 (4S)-4-decarboxylflavipesolide C (1)、1-(2,2-二甲基苯并二氢吡喃-6y1)-3-(4-羟苯基)propan-2-one (2)、 (R,E)-3-(2,2-二甲基色满-6-y1)-4-羟基-5-((2-(2羟基丙烷-2-y1)-2,3-二氢苯并呋喃-5-基)亚甲基)呋喃-2(5H)-酮(3)、(R)-2-(2-(2羟基丙-2-基)-2,3-二氢苯并呋喃-5-基)乙酸甲酯(4)，以及使用 10 μM 曲古抑菌素 A (TSA) 从土曲霉 OUCMDZ-2739 的化学表观遗传培养物中分离出九种已知化合物 (5-13)。在没有 TSA 的相同条件下，A. terreus OUCMDZ-2739 产生了不同的化合物 (14-20)，支持真菌的化学表观遗传修饰可以丰富真菌产物的化学多样性。观察到化合物8针对K562细胞、9针对MCF-7和K562细胞以及12针对MCF-7细胞的细胞毒性，IC50值分别为9.5、10.1、13.0和8.5μM。化合物3、8和17表现出比1-脱氧野尻霉素和阿卡波糖（阳性对照）更强的n-葡萄糖苷酶抑制作用，IC50值分别为24.8、1.2、61.6、191.7和555.1μM。酶动力学研究进一步表明化合物8是一种抗竞争抑制剂，Ki值为1.42 mu M。 (C) 2017 Elsevier Ltd. 版权所有。
Four new meroterpenoids identified as (4S)-4-decarboxylflavipesolide C (1), 1-(2,2-dimethylchroman-6y1)-3-(4-hydroxyphenyl)propan-2-one (2), (R,E)-3-(2,2-dimethylchroman-6-y1)-4-hydroxy-5-((2-(2hydroxypropan-2-y1)-2,3-dihydrobenzofuran-5-yl)methylene)furan-2(5H)-one (3), methyl (R)-2-(2-(2hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl) acetate (4), along with nine known compounds (5-13) were isolated from a chemical-epigenetic culture of Aspergillus terreus OUCMDZ-2739 with 10 mu M trichostatin A (TSA). Under the same condition without TSA, A. terreus OUCMDZ-2739 produced different compounds (14-20), supporting that the chemical-epigenetic modification of fungi could enrich the chemodiversity of the fungal products. The cytotoxicity was observed for compound 8 against K562 cell, 9 against MCF-7 and K562 cells and 12 against MCF-7 cell with IC50 values of 9.5, 10.1, 13.0 and 8.5 mu M, respectively. Compounds 3, 8 and 17 exhibited stronger n-glucosidase inhibition than 1deoxynojirimycin and acarbose (positive controls) with IC50 values of 24.8, 1.2, 61.6, 191.7 and 555.1 mu M, respectively. The enzyme kinetics study further indicated that compound 8 was an anticompetitive inhibitor with Ki value of 1.42 mu M. (C) 2017 Elsevier Ltd. All rights reserved.