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固醇调节元件结合蛋白 Sre1 调控红酵母中的类胡萝卜素生物合成。

Sterol regulatory element-binding protein Sre1 regulates carotenogenesis in the red yeast .

机构信息

Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.

Centro de Biotecnología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.

出版信息

J Lipid Res. 2020 Dec;61(12):1658-1674. doi: 10.1194/jlr.RA120000975. Epub 2020 Sep 15.

Abstract

is a basidiomycete yeast that produces carotenoids, mainly astaxanthin. Astaxanthin is an organic pigment of commercial interest due to its antioxidant and coloring properties. has a functional SREBP pathway, and the Sre1 protein is the SREBP homolog in this yeast. However, how sterol regulatory element (Sre)1 promotes the biosynthesis of sterols and carotenoids in is unknown. In this work, comparative RNA-sequencing analysis between modified strains that have an active Sre1 protein and the WT was performed to identify Sre1-dependent genes. In addition, Sre1 direct target genes were identified through ChIP combined with lambda exonuclease digestion (ChIP-exo) assays. SRE motifs were detected in the promoter regions of several Sre1 direct target genes and were consistent with the SREs described in other yeast species. Sre1 directly regulates genes related to ergosterol biosynthesis as well as genes related to the mevalonate (MVA) pathway, which synthesizes the building blocks of isoprenoids, including carotenoids. Two carotenogenic genes, and , were also identified as Sre1 direct target genes. Thus, carotenogenesis in is regulated by Sre1 through the regulation of the MVA pathway and the regulation of the and genes. As the gene encodes a cytochrome P450 reductase, Sre1 regulates pathways that include cytochrome P450 enzymes, such as the biosynthesis of carotenoids and sterols. These results demonstrate that Sre1 is a sterol master regulator that is conserved in .

摘要

是一种担子菌酵母,可产生类胡萝卜素,主要是虾青素。虾青素是一种具有商业价值的有机色素,因其具有抗氧化和着色特性而受到关注。具有功能性 SREBP 途径,Sre1 蛋白是该酵母中的 SREBP 同源物。然而,固醇调节元件 (Sre)1 如何促进固醇和类胡萝卜素在中的生物合成尚不清楚。在这项工作中,对具有活性 Sre1 蛋白的修饰和 WT 之间进行了比较 RNA 测序分析,以鉴定 Sre1 依赖性基因。此外,通过 ChIP 结合 lambda 外切核酸酶消化 (ChIP-exo) 测定鉴定了 Sre1 直接靶基因。在几个 Sre1 直接靶基因的启动子区域检测到 SRE 基序,并且与其他酵母物种中描述的 SRE 一致。Sre1 直接调节与麦角固醇生物合成以及与甲羟戊酸 (MVA) 途径相关的基因,该途径合成类异戊二烯的构建块,包括类胡萝卜素。两个类胡萝卜素生物合成基因和也被鉴定为 Sre1 直接靶基因。因此,通过调节 MVA 途径和调节和基因,Sre1 调节中的类胡萝卜素生物合成。由于基因编码细胞色素 P450 还原酶,Sre1 调节包括细胞色素 P450 酶在内的途径,例如类胡萝卜素和固醇的生物合成。这些结果表明,Sre1 是一种固醇主调节剂,在中保守。

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