Prototheca spp. are achlorophyllous algae, ubiquitous in nature. An increasing number of human and animal cases of Prototheca infection (protothecosis) are reported, and antifungal azoles, which inhibit sterol 14α-demethylase (CYP51/ERG11) involved in ergosterol biosynthesis, have empirically been used for the treatment of protothecosis. Although Prototheca, like fungi, has ergosterol in the cell membrane, efficacy of the antifungal azoles in the treatment of protothecosis is controversial. For investigating the interaction of azole drugs with Prototheca CYP51/ERG11, the CYP51/ERG11 genomic genes of four strains of P. wickerhamii and one strain each of P. cutis and P. miyajii were isolated and characterized in this study. Compared with the CYP51/ERG11 gene of chlorophyllous Auxenochlorella Protothecoides, it is possible that ProtothecaCYP51/ERG11 gene, whose exon-intron structure appeared to be species-specific, lost introns associated with the loss of photosynthetic activity. Analysis of the deduced amino acid sequences revealed that Prototheca CYP51/ERG11 and fungal CYP51/ERG11 are phylogenetically distant from each other although their overall structures are similar. Our basic in silico studies predicted that antifungal azoles could bind to the catalytic pocket of Prototheca CYP51/ERG11. It was also suggested that amino acid residues away from the catalytic pocket might affect the drug susceptibility. The results of this study may provide useful insights into the phylogenetic taxonomy of Prototheca spp. in relationship to the CYP51/ERG11 structure and development of novel therapeutic drugs for the treatment of protothecosis. Lay Summary Cases of infection by microalgae of Prototheca species are increasing. However, effective treatment has not been established yet. In this study, gene and structure of Prototheca’s CYP51/ERG11, an enzyme which might serve as a target for therapeutic drugs, were characterized for the first time.

中文翻译：

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Prototheca CYP51/ERG11 作为治疗药物可能靶点的表征

原藻属 是叶绿素藻类，在自然界中无处不在。据报道，越来越多的人和动物感染原藻感染（原藻病），并且抑制参与麦角甾醇生物合成的甾醇 14α-去甲基化酶 (CYP51/ERG11) 的抗真菌唑类药物已被经验性地用于治疗原藻病。尽管原藻与真菌一样，在细胞膜中含有麦角甾醇，但抗真菌唑类药物在治疗原藻的疗效存在争议。为了研究唑类药物与 Prototheca CYP51/ERG11 的相互作用，本研究分离并鉴定了四种 P. wickerhamii 菌株和 P. cutis 和 P. miyajii 各菌株的 CYP51/ERG11 基因组基因。与叶绿素原壳小球藻的 CYP51/ERG11 基因相比，ProtothecaCYP51/ERG11 基因的外显子-内含子结构似乎是物种特异性的，它可能会丢失与光合活性丧失相关的内含子。对推导的氨基酸序列的分析表明，尽管它们的整体结构相似，但原藻 CYP51/ERG11 和真菌 CYP51/ERG11 在系统发育上彼此远离。我们的基础计算机研究预测抗真菌唑类可以与 Prototheca CYP51/ERG11 的催化口袋结合。也有人提出远离催化袋的氨基酸残基可能会影响药物敏感性。这项研究的结果可能为 Prototheca spp 的系统发育分类学提供有用的见解。与 CYP51/ERG11 结构的关系以及治疗原皮病的新型治疗药物的开发。简述 原藻属微藻感染的病例正在增加。但是，目前还没有建立有效的治疗方法。在这项研究中，首次对 Prototheca 的 CYP51/ERG11（一种可能作为治疗药物靶点的酶）的基因和结构进行了表征。