Candida glabrata is a high-performance microbial cell factory for the production of organic acids. To elucidate the role of the C. glabrata Mediator tail subunit Med2 (CgMed2) at pH 2.0, we deleted or overexpressed CgMed2 and used transcriptome analysis to identify genes that are regulated by CgMed2. At pH 2.0, the deletion of CgMed2 resulted in a cell growth decrease of 26.1% and a survival decrease of 32.3%. Overexpression of CgMed2 increased cell growth by 12.4% and cell survival by 5.9% compared to the wild-type strain. Transcriptome and phenotypic analyses identified CgYap6 as a transcription factor involved in acid pH stress tolerance. Deletion of CgYap6 caused growth defects, whereas its overexpression enhanced cell growth at pH 2.0. Furthermore, total glycerophospholipid content and membrane integrity decreased by 33.4% and 21.8%, respectively, in the CgMed2Δ strain; however, overexpression of CgMed2 increased the total glycerophospholipid content and membrane integrity by 24.7% and 12.1%, respectively, compared with those of the wild-type strain at pH 2.0. These results demonstrated that under acid pH stress, CgMed2 physically interacts with CgYap6, which translocates from the cytoplasm to the nucleus after being phosphorylated by the protein kinase CgYak1. Once in the nucleus, CgYap6 recruits CgMed2 to express glycerophospholipid-related genes. Our study elucidated the function of CgMed2 under acid pH stress and provides a potential strategy to equip Candida glabrata with low-pH resistance during organic acid fermentation.

中文翻译：

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光滑念珠菌Yap6招募Med2来改变甘油磷脂的组成并开发耐酸性pH胁迫

光滑念珠菌是一种用于生产有机酸的高性能微生物细胞工厂。为了阐明在pH 2.0时，光滑的C. glabrata介体尾部亚基Med2（Cg Med2）的作用，我们删除或过度表达了Cg Med2，并使用转录组分析来鉴定受Cg Med2调控的基因。在pH 2.0下，Cg Med2的缺失导致细胞生长下降26.1％，存活率下降32.3％。与野生型菌株相比，Cg Med2的过表达使细胞生长提高了12.4％，细胞存活率提高了5.9％。转录组和表型分析鉴定出CgYap6作为参与酸性pH胁迫耐受性的转录因子。Cg Yap6的缺失会导致生长缺陷，而其过表达会增强pH 2.0下的细胞生长。此外，总甘油含量和膜完整性分别降低33.4％和21.8％，在CG Med2Δ菌株; 然而，与pH 2.0的野生型菌株相比，Cg Med2的过量表达分别使总甘油磷脂含量和膜完整性分别提高了24.7％和12.1％。这些结果表明，在酸性pH胁迫下，Cg Med2与Cg Yap6发生物理相互作用，后者在被蛋白激酶Cg磷酸化后从细胞质迁移至细胞核。k牛1。一旦进入细胞核，Cg Yap6就会募集Cg Med2来表达与甘油磷脂相关的基因。我们的研究阐明了Cg Med2在酸性pH胁迫下的功能，并提供了在有机酸发酵过程中使光滑念珠菌具有低pH耐受性的潜在策略。