State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Department of Biology and Biological Engineering, Chalmers University of Technology, SE41296, Gothenburg, Sweden.
Nat Commun. 2022 May 20;13(1):2819. doi: 10.1038/s41467-022-30513-2.
Saccharomyces cerevisiae is a widely used cell factory; therefore, it is important to understand how it organizes key functional parts when cultured under different conditions. Here, we perform a multiomics analysis of S. cerevisiae by culturing the strain with a wide range of specific growth rates using glucose as the sole limiting nutrient. Under these different conditions, we measure the absolute transcriptome, the absolute proteome, the phosphoproteome, and the metabolome. Most functional protein groups show a linear dependence on the specific growth rate. Proteins engaged in translation show a perfect linear increase with the specific growth rate, while glycolysis and chaperone proteins show a linear decrease under respiratory conditions. Glycolytic enzymes and chaperones, however, show decreased phosphorylation with increasing specific growth rates; at the same time, an overall increased flux through these pathways is observed. Further analysis show that even though mRNA levels do not correlate with protein levels for all individual genes, the transcriptome level of functional groups correlates very well with its corresponding proteome. Finally, using enzyme-constrained genome-scale modeling, we find that enzyme usage plays an important role in controlling flux in amino acid biosynthesis.
酿酒酵母是一种广泛应用的细胞工厂；因此，了解其在不同条件下培养时如何组织关键功能部分非常重要。在这里，我们通过使用葡萄糖作为唯一限制营养物质，以广泛的特定生长速率培养该菌株，对酿酒酵母进行了多组学分析。在这些不同的条件下，我们测量了绝对转录组、绝对蛋白质组、磷酸化蛋白质组和代谢组。大多数功能蛋白组与特定生长速率呈线性关系。参与翻译的蛋白质与特定生长速率呈完美的线性增加，而在呼吸条件下糖酵解和伴侣蛋白呈线性下降。然而，糖酵解酶和伴侣蛋白的磷酸化随特定生长速率的增加而降低；同时，这些途径的整体通量增加。进一步的分析表明，尽管mRNA 水平与所有单个基因的蛋白质水平都不相关，但功能组的转录组水平与其相应的蛋白质组非常相关。最后，使用酶约束的基因组尺度建模，我们发现酶的使用在控制氨基酸生物合成中的通量方面起着重要作用。
