在构巢曲霉中重新设计一个氮杂菲酮生物合成途径来产生脂氧合酶抑制剂。
Reengineering an azaphilone biosynthesis pathway in Aspergillus nidulans to create lipoxygenase inhibitors.
机构信息
Department of Chemistry, University of Southern California, College of Letters, Arts and Sciences, Los Angeles, California 90089, USA.
出版信息
Org Lett. 2012 Feb 17;14(4):972-5. doi: 10.1021/ol203094k. Epub 2012 Feb 1.
Abstract
Sclerotiorin, an azaphilone polyketide, is a bioactive natural product known to inhibit 15-lipoxygenase and many other biological targets. To readily access sclerotiorin and analogs, we developed a 2-3 step semisynthetic route to produce a variety of azaphilones starting from an advanced, putative azaphilone intermediate (5) overproduced by an engineered strain of Aspergillus nidulans. The inhibitory activities of the semisynthetic azaphilones against 15-lipoxygenase were evaluated with several compounds displaying low micromolar potency.
摘要
栓菌酮，一种氮杂菲酮聚酮，是一种具有生物活性的天然产物，已知能抑制 15-脂氧合酶和许多其他生物靶点。为了方便获得栓菌酮及其类似物，我们开发了一种 2-3 步半合成路线，从工程化的构巢曲霉菌株过度产生的一种先进的、假定的氮杂菲酮中间产物（5）开始，生产各种氮杂菲酮。用几种具有低微摩尔效力的化合物评估了半合成氮杂菲酮对 15-脂氧合酶的抑制活性。
相似文献
1
Reengineering an azaphilone biosynthesis pathway in Aspergillus nidulans to create lipoxygenase inhibitors.在构巢曲霉中重新设计一个氮杂菲酮生物合成途径来产生脂氧合酶抑制剂。
Org Lett. 2012 Feb 17;14(4):972-5. doi: 10.1021/ol203094k. Epub 2012 Feb 1.
2
Core Steps to the Azaphilone Family of Fungal Natural Products.真菌天然产物吖啶酮家族的核心步骤。
Chembiochem. 2021 Nov 3;22(21):3027-3036. doi: 10.1002/cbic.202100240. Epub 2021 Jul 9.
3
Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro.氮杂环庚三烯酮在体外可抑制tau蛋白聚集并溶解tau蛋白聚集体。
ACS Chem Neurosci. 2015 May 20;6(5):751-60. doi: 10.1021/acschemneuro.5b00013. Epub 2015 Apr 15.
4
Pleiotropically activation of azaphilone biosynthesis by overexpressing a pathway-specific transcription factor in marine-derived Aspergillus terreus RA2905.通过在海洋来源的土曲霉RA2905中过表达一条途径特异性转录因子来多效性激活氮杂蒽酮生物合成。
Bioorg Chem. 2024 Dec;153:107832. doi: 10.1016/j.bioorg.2024.107832. Epub 2024 Sep 19.
5
Azaphilones from the Red Sea Fungus .红海真菌中的氮杂菲酮
Mar Drugs. 2020 Apr 10;18(4):204. doi: 10.3390/md18040204.
6
Cohaerins G-K, azaphilone pigments from Annulohypoxylon cohaerens and absolute stereochemistry of cohaerins C-K.共头菌素 G-K，来自胶韧革菌的吖啶酮类色素及共头菌素 C-K 的绝对立体化学。
Phytochemistry. 2013 Nov;95:252-8. doi: 10.1016/j.phytochem.2013.07.027. Epub 2013 Aug 19.
7
Azaphilones with protein tyrosine phosphatase inhibitory activity isolated from the fungus Aspergillus deflectus.从真菌黄曲霉中分离得到具有蛋白酪氨酸磷酸酶抑制活性的氮杂菲酮。
Phytochemistry. 2020 Feb;170:112224. doi: 10.1016/j.phytochem.2019.112224. Epub 2019 Dec 5.
8
Bioactive Azaphilone Derivatives from the Fungus Talaromyces aculeatus.来自真菌刺孢篮状菌的生物活性氮杂蒽酮衍生物
J Nat Prod. 2017 Aug 25;80(8):2199-2203. doi: 10.1021/acs.jnatprod.7b00032. Epub 2017 Jul 27.
9
Azaphilone pigments from a yellow mutant of the fungus Monascus kaoliang.来自红曲霉菌黄色突变体的氮杂环庚三烯酮色素。
Phytochemistry. 2004 Sep;65(18):2569-75. doi: 10.1016/j.phytochem.2004.08.032.
10
Bioactive hydrogenated azaphilones from acid-tolerant fungus Penicillium purpureum OUCMDZ-019.来自耐酸真菌紫青霉OUCMDZ - 019的生物活性氢化氮杂蒽酮类化合物。
J Antibiot (Tokyo). 2025 Apr;78(5):281-287. doi: 10.1038/s41429-025-00818-7. Epub 2025 Mar 24.
引用本文的文献
1
Bioactive hydrogenated azaphilones from acid-tolerant fungus Penicillium purpureum OUCMDZ-019.来自耐酸真菌紫青霉OUCMDZ - 019的生物活性氢化氮杂蒽酮类化合物。
J Antibiot (Tokyo). 2025 Apr;78(5):281-287. doi: 10.1038/s41429-025-00818-7. Epub 2025 Mar 24.
2
Asymmetric Total Synthesis of Chaetoglobin A.不对称全合成 Chaetoglobin A。
J Org Chem. 2023 Jun 2;88(11):6691-6703. doi: 10.1021/acs.joc.3c00002. Epub 2023 May 17.
3
Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi.联合 OSMAC、代谢组学和基因组学方法生产和注释白蚁共生真菌中的卤代吖啶酮和伊利西醇。
Sci Rep. 2022 Oct 15;12(1):17310. doi: 10.1038/s41598-022-22256-3.
4
Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining.通过异源表达和基因组挖掘破译真菌天然产物生物合成的化学逻辑。
Nat Prod Rep. 2023 Jan 25;40(1):89-127. doi: 10.1039/d2np00050d.
5
Chemoenzymatic Total Synthesis of Natural Products.天然产物的化学酶法全合成。
Acc Chem Res. 2021 Mar 16;54(6):1374-1384. doi: 10.1021/acs.accounts.0c00810. Epub 2021 Feb 18.
6
New azaphilones from Aspergillus neoglaber.来自新光滑曲霉的新型氮杂蒽酮类化合物。
AMB Express. 2020 Aug 17;10(1):145. doi: 10.1186/s13568-020-01078-4.
7
Identification and Validation of an Secondary Metabolite Derivative as an Inhibitor of the Musashi-RNA Interaction.一种次生代谢物衍生物作为武藏-RNA相互作用抑制剂的鉴定与验证。
Cancers (Basel). 2020 Aug 8;12(8):2221. doi: 10.3390/cancers12082221.
8
Stereodivergent, Chemoenzymatic Synthesis of Azaphilone Natural Products.立体发散的，轴手性酶法合成氮杂菲酮天然产物。
J Am Chem Soc. 2019 Nov 20;141(46):18551-18559. doi: 10.1021/jacs.9b09385. Epub 2019 Nov 6.
9
Recent development of lipoxygenase inhibitors as anti-inflammatory agents.脂氧合酶抑制剂作为抗炎剂的最新进展。
Medchemcomm. 2017 Nov 29;9(2):212-225. doi: 10.1039/c7md00390k. eCollection 2018 Feb 1.
10
Preparation, Structure, and Potent Antifouling Activity of Sclerotioramine Derivatives.鞘氨醇胺衍生物的制备、结构和强效抗污活性。
Mar Biotechnol (NY). 2017 Aug;19(4):372-378. doi: 10.1007/s10126-017-9760-x. Epub 2017 Jul 7.
本文引用的文献
1
Synthesis of the azaphilones (+)-sclerotiorin and (+)-8-O-methylsclerotiorinamine utilizing (+)-sparteine surrogates in copper-mediated oxidative dearomatization.利用（+）-藜芦碱类似物在铜介导的氧化去芳构化反应中合成氮杂菲酮（+）-白僵菌素和（+）-8-O-甲基白僵菌素胺。
J Org Chem. 2011 Apr 15;76(8):2577-84. doi: 10.1021/jo102448n. Epub 2011 Mar 14.
2
IBX-I2 redox couple for facile generation of IOH and I+: expedient protocol for iodohydroxylation of olefins and iodination of aromatics.IBX-I2 氧化还原对可方便地生成 IOH 和 I+：烯烃的碘羟化和芳环的碘化的便捷方法。
J Org Chem. 2009 Aug 21;74(16):6287-90. doi: 10.1021/jo9007892.
3
A gene cluster containing two fungal polyketide synthases encodes the biosynthetic pathway for a polyketide, asperfuranone, in Aspergillus nidulans.一个包含两个真菌聚酮合酶的基因簇编码了 Aspergillus nidulans 中多酮类化合物 Asperfuranone 的生物合成途径。
J Am Chem Soc. 2009 Mar 4;131(8):2965-70. doi: 10.1021/ja8088185.
4
Control of oxygenation in lipoxygenase and cyclooxygenase catalysis.脂氧合酶和环氧化酶催化过程中的氧合作用控制。
Chem Biol. 2007 May;14(5):473-88. doi: 10.1016/j.chembiol.2007.04.007.
5
Sclerotiorin, a novel inhibitor of lipoxygenase from Penicillium frequentans.
J Agric Food Chem. 2007 Apr 18;55(8):2879-83. doi: 10.1021/jf062032x. Epub 2007 Mar 27.
6
Asymmetric syntheses of (-)-mitorubrin and related azaphilone natural products.（-）-米托鲁宾及相关氮杂稠酮天然产物的不对称合成。
Org Lett. 2006 Oct 26;8(22):5169-71. doi: 10.1021/ol062233m.
7
Total synthesis of (+/-)-mitorubrinic acid.（±）-米托蒽醌酸的全合成。
Org Lett. 2006 Aug 3;8(16):3481-3. doi: 10.1021/ol0610993.
8
Sclerotiorine, C(20)H(20)O(5)Cl, a chlorine-containing metabolic product of Penicillium sclerotiorum van Beyma.核盘菌素，C(20)H(20)O(5)Cl，是核盘青霉（van Beyma）的一种含氯代谢产物。
Biochem J. 1940 Nov;34(10-11):1418.1-1421. doi: 10.1042/bj0341418.
9
Synthesis of the azaphilones using copper-mediated enantioselective oxidative dearomatization.利用铜介导的对映选择性氧化脱芳构化反应合成氮杂蒽酮类化合物。
J Am Chem Soc. 2005 Jul 6;127(26):9342-3. doi: 10.1021/ja052049g.
10
Synthesis studies toward chloroazaphilone and vinylogous gamma-pyridones: two common natural product core structures.氯氮杂蒽酮和乙烯基γ-吡啶酮的合成研究：两种常见的天然产物核心结构。
J Org Chem. 2005 Jun 10;70(12):4585-90. doi: 10.1021/jo050414g.
Zotero 插件