PKA regulatory subunit Bcy1 couples growth, lipid metabolism, and fermentation during anaerobic xylose growth in Saccharomyces cerevisiae.

IF 4.5 2区 生物学 Q1 Agricultural and Biological Sciences PLoS Genetics Pub Date : 2023-07-01 DOI:10.1371/journal.pgen.1010593
Ellen R Wagner, Nicole M Nightingale, Annie Jen, Katherine A Overmyer, Mick McGee, Joshua J Coon, Audrey P Gasch
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引用次数: 1

Abstract

Organisms have evolved elaborate physiological pathways that regulate growth, proliferation, metabolism, and stress response. These pathways must be properly coordinated to elicit the appropriate response to an ever-changing environment. While individual pathways have been well studied in a variety of model systems, there remains much to uncover about how pathways are integrated to produce systemic changes in a cell, especially in dynamic conditions. We previously showed that deletion of Protein Kinase A (PKA) regulatory subunit BCY1 can decouple growth and metabolism in Saccharomyces cerevisiae engineered for anaerobic xylose fermentation, allowing for robust fermentation in the absence of division. This provides an opportunity to understand how PKA signaling normally coordinates these processes. Here, we integrated transcriptomic, lipidomic, and phospho-proteomic responses upon a glucose to xylose shift across a series of strains with different genetic mutations promoting either coupled or decoupled xylose-dependent growth and metabolism. Together, results suggested that defects in lipid homeostasis limit growth in the bcy1Δ strain despite robust metabolism. To further understand this mechanism, we performed adaptive laboratory evolutions to re-evolve coupled growth and metabolism in the bcy1Δ parental strain. The evolved strain harbored mutations in PKA subunit TPK1 and lipid regulator OPI1, among other genes, and evolved changes in lipid profiles and gene expression. Deletion of the evolved opi1 gene partially reverted the strain's phenotype to the bcy1Δ parent, with reduced growth and robust xylose fermentation. We suggest several models for how cells coordinate growth, metabolism, and other responses in budding yeast and how restructuring these processes enables anaerobic xylose utilization.

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PKA调控亚基Bcy1在酿酒酵母厌氧木糖生长过程中对生长、脂质代谢和发酵进行耦合。
生物体已经进化出复杂的生理途径来调节生长、增殖、代谢和应激反应。这些途径必须得到适当的协调,以引起对不断变化的环境的适当反应。虽然在各种模型系统中已经对单个通路进行了很好的研究,但关于通路如何整合以在细胞中产生系统变化,特别是在动态条件下,仍有许多有待发现。我们之前的研究表明,蛋白激酶A (PKA)调控亚基BCY1的缺失可以使酿酒酵母的生长和代谢解耦,从而在没有分裂的情况下实现强劲的发酵。这为了解PKA信号通常如何协调这些过程提供了机会。在这里,我们整合了转录组学、脂质组学和磷酸化蛋白质组学对葡萄糖向木糖转变的反应,这些反应跨越了一系列具有不同基因突变的菌株,促进了偶联或解耦的木糖依赖性生长和代谢。总之,结果表明脂质稳态缺陷限制了bcy1Δ菌株的生长,尽管代谢强劲。为了进一步了解这一机制,我们进行了适应性实验室进化,重新进化了bcy1Δ亲本菌株的耦合生长和代谢。进化后的菌株在PKA亚基TPK1和脂质调节因子OPI1等基因中发生突变,并在脂质谱和基因表达方面发生了变化。进化的opi1基因的缺失使菌株的表型部分恢复到bcy1Δ亲本,生长减少,木糖发酵强劲。我们提出了几种细胞如何协调生长、代谢和其他反应的模型,以及如何重组这些过程使厌氧木糖利用。
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来源期刊
PLoS Genetics
PLoS Genetics 生物-遗传学
CiteScore
8.10
自引率
2.20%
发文量
438
审稿时长
1 months
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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