To explore the differences in the intracellular transcriptional mechanism in carbon-derepressed and wild-type Pichia pastoris strains fed with three different carbon sources. RNA in carbon-derepressed (Δmig1Δmig2Δnrg1-Mit1; Mut) and wild-type (WT) P. pastoris fed with three different carbon sources (dextrose, glycerol, and methanol) were sequenced. Differentially expressed genes (DEGs) associated with these carbon sources were obtained and clustered into modules using weighted gene co-expression network analysis (WGCNA). Signaling pathway enrichment analysis was performed using KEGG, and protein to protein interaction (PPI) network was also constructed. A total of 2536 DEGs were obtained from three intersections, and some of them were enriched in carbon sources and involved in carbon metabolism, secondary metabolisms, and amino acid biosynthesis. Two modules, MEgreenyellow (involved in protease, oxidative phosphorylation, endoplasmic reticulum protein processing, folate carbon pool, and glycerol phospholipid metabolism pathways) and MEmidnightblue (involved in protease, endocytosis, steroid biosynthesis, and hippo signaling pathways) were significantly correlated with the strain type. Eight hub genes and two sub-networks were obtained from PPI network. Sub-network A enriched in proteasomes pathway while sub-network B enriched in ribosome pathway. The genes involved in carbon metabolism, secondary metabolic, and amino acid biosynthesis pathways changed significantly under different carbon sources. The changes in proteasome and ribosome activities play roles in carbohydrate metabolism in the methanol-free P_AOX1 start-up Mut strain.

中文翻译：

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具有反式作用元件工程的AOX1启动子下巴斯德毕赤酵母中甲醇非依赖性蛋白表达的转录调控网络

探讨碳抑制和野生型毕赤酵母菌株饲喂三种不同碳源的细胞内转录机制的差异。碳抑制的（Δmig1Δmig2Δnrg1-Mit1; Mut）和野生型（WT）P中的RNA 。巴斯德对三种不同碳源（葡萄糖，甘油和甲醇）的供料进行了测序。获得了与这些碳源相关的差异表达基因（DEG），并使用加权基因共表达网络分析（WGCNA）将其聚类为模块。使用KEGG进行信号通路富集分析，并构建了蛋白质与蛋白质相互作用（PPI）网络。从三个交叉点总共获得了2536个DEG，其中一些富含碳源，并且参与了碳代谢，次级代谢和氨基酸生物合成。两个模块，MEgreenyellow（涉及蛋白酶，氧化磷酸化，内质网蛋白加工，叶酸碳库和甘油磷脂代谢途径）和MEmidnightblue（涉及蛋白酶，内吞作用，类固醇生物合成和河马信号通路）与菌株类型显着相关。从PPI网络获得了八个集线器基因和两个子网络。子网A富含蛋白酶体途径，子网B富含核糖体途径。在不同碳源下，参与碳代谢，次级代谢和氨基酸生物合成途径的基因发生了显着变化。蛋白酶体和核糖体活性的变化在无甲醇磷中的碳水化合物代谢中起作用 不同碳源下氨基酸的生物合成途径发生了显着变化。蛋白酶体和核糖体活性的变化在无甲醇磷中的碳水化合物代谢中起作用 不同碳源下氨基酸的生物合成途径发生了显着变化。蛋白酶体和核糖体活性的变化在无甲醇磷中的碳水化合物代谢中起作用_AOX1启动Mut菌株。