{"title":"从一种海洋衍生真菌 Arthrinium arundinis 菌株中提取的具有抗炎和神经保护作用的 α-Pyrones 及其异源表达","authors":"Yiwei Hu, Xiaoyang Zhao, Yue Song, Jiahui Jiang, Ting Long, Mengjing Cong, Yuhua Miao, Yonghong Liu, Zhiyou Yang, Yiguang Zhu, Junfeng Wang","doi":"10.1021/acs.jnatprod.4c00393","DOIUrl":null,"url":null,"abstract":"Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (<b>1</b> and <b>2</b>) and four known (<b>3</b>–<b>6</b>) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus <i>Arthrinium arundinis</i>. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (<i>alt</i>) for alternapyrones was identified from <i>A. arundinis</i> ZSDS-F3 and validated by heterologous expression in <i>Aspergillus nidulans</i> A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2′ could convert the methyl group 26-CH<sub>3</sub> to a carboxyl group to produce <b>4</b> from <b>3</b>. Another cytochrome P450 monooxygenase, Alt3′, catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce <b>1</b>, <b>2</b>, <b>5</b>, and <b>6</b> from <b>4</b>. Alternapyrone G (<b>1</b>) 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.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression\",\"authors\":\"Yiwei Hu, Xiaoyang Zhao, Yue Song, Jiahui Jiang, Ting Long, Mengjing Cong, Yuhua Miao, Yonghong Liu, Zhiyou Yang, Yiguang Zhu, Junfeng Wang\",\"doi\":\"10.1021/acs.jnatprod.4c00393\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (<b>1</b> and <b>2</b>) and four known (<b>3</b>–<b>6</b>) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus <i>Arthrinium arundinis</i>. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (<i>alt</i>) for alternapyrones was identified from <i>A. arundinis</i> ZSDS-F3 and validated by heterologous expression in <i>Aspergillus nidulans</i> A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2′ could convert the methyl group 26-CH<sub>3</sub> to a carboxyl group to produce <b>4</b> from <b>3</b>. Another cytochrome P450 monooxygenase, Alt3′, catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce <b>1</b>, <b>2</b>, <b>5</b>, and <b>6</b> from <b>4</b>. Alternapyrone G (<b>1</b>) 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.\",\"PeriodicalId\":47,\"journal\":{\"name\":\"Journal of Natural Products \",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Natural Products \",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jnatprod.4c00393\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jnatprod.4c00393","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression
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.
期刊介绍:
The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
When new compounds are reported, manuscripts describing their biological activity are much preferred.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.