异源的
米曲霉
化学
异源表达
生物测定
立体化学
萜烯
拉伤
EC50型
曲霉
基因
生物化学
酶
体外
微生物学
生物
遗传学
重组DNA
解剖
作者
Wencong Yang,Tao Chen,Yan Chen,Qian Tan,Yanghui Ou,Gang Li,Bo Wang,Dan Hu,Hongliang Yao,Zhigang She
标识
DOI:10.1021/acs.joc.2c02501
摘要
The synthetic biology approach enables efficient and directional mining of target compounds during drug discovery. Ten new asperterpenoids (6-15) and five known analogues (1-5), possessing a rare 5/7/3/6/5 skeleton, were obtained from two Aspergillus oryzae transformants with heterologous expression of a terpene cyclase gene AstC with one or two P450 genes AstB/A under the guidance of molecular networking. Their planar structures were determined by 1D and 2D NMR and HR-ESI-MS. The absolute configurations of compounds 6 and 9-13 were determined by single crystal X-ray diffraction, and those of compounds 7-8 and 14-15 were compared with the ECD of known compounds. Seven of all the compounds are the first asperterpenoid oxidation products at C-17 or at C-25. In bioassay, compounds 1-2, 4-5, and 6-8 displayed moderate to strong eliminating activities against chloroquine-sensitive strain (P.f.3D7) with EC50 values ranging from 2.1 to 19.3 μM. The structure-activity relationship (SAR) was discussed, which showed that substituents at C-3, C-11, C-17, C-18, and C-23 of asperterpenoids significantly affected anti-plasma parasite activity.
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