Bysspectin A, an unusual octaketide dimer and the precursor derivatives from the endophytic fungus Byssochlamys spectabilis IMM0002 and their biological activities.
Bysspectin A, an unusual octaketide dimer and the precursor derivatives from the endophytic fungus Byssochlamys spectabilis IMM0002 and their biological activities.
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DOI：
10.1016/j.ejmech.2018.01.030
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发表时间：
2018-02
影响因子：
6.7
通讯作者：
Yuzhuo Wu;Huawei Zhang;Zhao-Hui Sun;J. Dai;Youcai Hu;Rui Li;P. Lin;Guiyang Xia;Lingyan Wang
中科院分区：
文献类型：
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作者：
Yuzhuo Wu;Huawei Zhang;Zhao-Hui Sun;J. Dai;Youcai Hu;Rui Li;P. Lin;Guiyang Xia;Lingyan Wang
Bysspectin A (1) 是一种具有新型碳骨架的聚酮衍生的八酮化合物二聚体，以及两种新的前体衍生物，bysspectins B 和 C (2 和 3)，是从传统中药植物 Edgeworthia chrysantha 的叶组织中分离的内生真菌 Byssochlamys spectabilis 的有机提取物中获得的，以及已知的八酮化合物，拟青霉素 A (4)。它们的结构通过 HRMS、1D 和 2D NMR 光谱分析确定。提出了其生物合成途径的合理途径。测试了化合物 1-3 的抗菌活性。只有化合物3对大肠杆菌和金黄色葡萄球菌具有弱活性，MIC值分别为32和64μg/mL。进一步评价了化合物1和4对人羧酸酯酶(hCE1、hCE2)的抑制作用。结果表明，bysspectin A (1) 是一种新型、高选择性的 hCE2 抑制剂，IC50 值为 2.01μM。对接模拟还表明，活性化合物1通过氢键与hCE2的Ser-288（催化腔中的催化氨基酸）产生相互作用，揭示了其对hCE2的高度选择性抑制。
Bysspectin A (1), a polyketide-derived octaketide dimer with a novel carbon skeleton, and two new precursor derivatives, bysspectins B and C (2and3), were obtained from an organic extract of the endophytic fungus Byssochlamys spectabilis that had been isolated from a leaf tissue of the traditional Chinese medicinal plantEdgeworthia chrysantha, together with a known octaketide, paecilocin A (4). Their structures were determined by HRMS, 1D and 2D NMR spectroscopic analysis. A plausible route for their biosynthetic pathway is proposed. Compounds1–3were tested for their antimicrobial activities. Only compound3was weakly active againstEscherichia coliandStaphyloccocus aureuswith MIC values of 32 and 64μg/mL, respectively. Further, the inhibitory effects on human carboxylesterases (hCE1, hCE2) of compounds1and4were evaluated. The results demonstrated that bysspectin A (1) was a novel and highly selective inhibitor against hCE2 with the IC50value of 2.01 μM. Docking simulation also demonstrated that active compound1created interaction with the Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2viahydrogen bonding, revealing its highly selective inhibition toward hCE2.