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Linoleate diol synthase related enzymes of the human pathogens Histoplasma capsulatum and Blastomyces dermatitidis
Archives of Biochemistry and Biophysics ( IF 3.9 ) Pub Date : 2020-11-13 , DOI: 10.1016/j.abb.2020.108669
Ernst H. Oliw

Histoplasma capsulatum is an ascomyceteous fungus and a human lung pathogen, which is present in river valleys of the Americas and other continents. H. capsulatum and two related human pathogens, Blasmomyces dermatitidis and Paracoccidioides brasiliensis, belongs to the Ajellomycetaceae family. The genomes of all three species code for three homologous and tentative enzymes of the linoleate diol synthase (LDS) family of fusion enzymes with dioxygenase (DOX) and cytochrome P450 domains. One group aligned closely with 8R-DOX-5,8-LDS of Aspergilli, which oxidizes linoleic acid to 5S,8R-dihydroxylinoleic acid; this group was not further investigated. The second group aligned with 10R-DOX-epoxy alcohol synthase (EAS) of plant pathogens. Expression of this enzyme from B. dermatitidis revealed only 10R-DOX activities, i.e., oxidation of linoleic acid to 10R-hydroperoxy-8E,12Z-octadecadienoic acid. The third group aligned in a separate entity. Expression of these enzymes of H. capsulatum and B. dermatitidis revealed no DOX activities, but both enzymes transformed 13S-hydroperoxy-9Z,11E-octadecadienoic acid efficiently to 12(13S)epoxy-11-hydroperoxy-9Z-octadecenoic acid. Other 13-hydroperoxides of linoleic and α-linolenic acids were transformed with less efficiency and the 9-hydroperoxides of linoleic acid were not transformed. In conclusion, a novel EAS has been found in H. capsulatum and B. dermititidis with 13S-hydroperoxy-9Z,11E-octadecadienoic acid as the likely physiological substrate.



中文翻译:

人类病原体荚膜胞浆菌皮肤芽孢杆菌的亚油酸二醇合酶相关酶

荚膜组织胞浆菌是一种无囊真菌和人类肺部病原体,存在于美洲和其他大陆的河谷中。荚膜组织胞浆菌和两个相关的人类病原体,Blasmomyces皮炎巴西副,属于Ajellomycetaceae家庭。这三个物种的基因组均编码亚油酸二醇合酶(LDS)家族的三种同源和暂定酶,该酶具有双加氧酶(DOX)和细胞色素P450结构域。一组与曲霉菌的8 R -DOX-5,8-LDS紧密结合,后者将亚油酸氧化为5 S,8 R-二羟基亚油酸;该组没有进一步调查。第二组与植物病原体的10 R -DOX-环氧醇合酶(EAS)对齐。这种来自皮肤芽孢杆菌的酶的表达显示仅10 R -DOX活性,亚油酸氧化成10 R-氢过氧-8 E,12 Z-十八碳二烯酸。第三组在一个单独的实体中对齐。这些酶的荚膜芽孢杆菌皮肤病双歧杆菌的表达表明没有DOX活性,但两种酶都转化了13 S -hydroperoxy-9 Z,11 E-十八碳烯酸有效地形成12(13 S)环氧-11-氢过氧-9 Z-十八碳烯酸。亚油酸和α-亚麻酸的其他13-氢过氧化物转化效率较低,亚油酸的9-氢过氧化物未转化。总之,一种新颖的EAS已经发现荚膜组织胞浆菌B. dermititidis 13 š -hydroperoxy-9 Ž,11 é十八碳二烯酸为可能的生理底物。

更新日期:2020-11-19
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