单加氧酶
异源表达
羟基化
巢状曲霉
细胞色素P450
立体化学
异源的
神经保护
脂多糖
小胶质细胞
基因簇
化学
微生物学
生物
生物化学
基因
酶
炎症
药理学
重组DNA
内分泌学
突变体
免疫学
作者
Yiwei Hu,Xiaoyang Zhao,Song Yue,Jiahui Jiang,Ting Yu Long,Mengjing Cong,Yuhua Miao,Yonghong Liu,Zhiyou Yang,Yiguang Zhu,Junfeng Wang
标识
DOI:10.1021/acs.jnatprod.4c00393
摘要
Fungal linear polyketides, such as α-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 ΔSTΔEM, 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 Aβ treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.
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