Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden.
Genetics. 2012 Mar;190(3):885-929. doi: 10.1534/genetics.111.133306.
Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear.
自生化分析伊始,酵母一直是研究真核生物代谢调控的先驱模型。在过去的三十年中,强大的酵母遗传学和全基因组方法的结合,为代谢调控提供了更具综合性的视角。从超途径控制到单个基因反应,人们发现了多个层次的调控。已经确定了在感应细胞内外环境中起关键作用的组成型和专用系统,并且越来越意识到它们参与了蛋白质和代谢物在高度调控的细胞内区室化。本文重点介绍了氨基酸、核苷酸和磷酸盐代谢领域的最新进展,并提供了一些说明性示例,展示了酵母细胞如何结合多种机制来实现对多种代谢途径的协调调控。重要的是,已经出现了一些常见的方案,这些方案揭示了各种途径之间保守的机制,例如涉及代谢物感应以及非编码 RNA 或代谢中间产物的转录调控。由于酵母实验系统的显著复杂性,代谢组学和转录组学之间的紧密联系的图景正在变得清晰。