Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression

被引:5
作者
Hu, Yiwei [1 ,3 ]
Zhao, Xiaoyang [1 ,3 ]
Song, Yue [1 ,3 ]
Jiang, Jiahui [2 ]
Long, Ting [1 ]
Cong, Mengjing [1 ,3 ]
Miao, Yuhua [1 ]
Liu, Yonghong [1 ,3 ,4 ]
Yang, Zhiyou [2 ]
Zhu, Yiguang [1 ,3 ,4 ]
Wang, Junfeng [1 ,3 ,4 ]
机构
[1] Chinese Acad Sci, South China Sea Inst Oceanol, CAS Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, Guangzhou 510301, Peoples R China
[2] Guangdong Ocean Univ, Coll Food Sci & Technol, Guangdong Prov Engn Technol Res Ctr Seafood, Guangdong Prov Key Lab Aquat Prod Proc & Safety,Gu, Zhanjiang 524088, Peoples R China
[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[4] Sanya Inst Marine Ecol & Engn, Sanya 572000, Peoples R China
来源
JOURNAL OF NATURAL PRODUCTS | 2024年 / 87卷 / 08期
基金
海南省自然科学基金; 中国国家自然科学基金;
关键词
NATURAL-PRODUCTS; SYNTHASE; DISEASE;
D O I
10.1021/acs.jnatprod.4c00393
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Fungal linear polyketides, such as alpha-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1 and 2) and four known (3-6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 Delta ST Delta EM, which revealed that the cytochrome P450 monooxygenase Alt2 ' could convert the methyl group 26-CH3 to a carboxyl group to produce 4 from 3. Another cytochrome P450 monooxygenase, Alt3 ', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6 from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after A beta treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.
引用
收藏
页码:1975 / 1982
页数:8
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