Lahtvee Petri-Jaan, Kumar Rahul, Hallström Björn M, Nielsen Jens
Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
Mol Biol Cell. 2016 Aug 1;27(15):2505-14. doi: 10.1091/mbc.E16-03-0187. Epub 2016 Jun 15.
Yeast cell factories encounter physical and chemical stresses when used for industrial production of fuels and chemicals. These stresses reduce productivity and increase bioprocess costs. Understanding the mechanisms of the stress response is essential for improving cellular robustness in platform strains. We investigated the three most commonly encountered industrial stresses for yeast (ethanol, salt, and temperature) to identify the mechanisms of general and stress-specific responses under chemostat conditions in which specific growth rate-dependent changes are eliminated. By applying systems-level analysis, we found that most stress responses converge on mitochondrial processes. Our analysis revealed that stress-specific factors differ between applied stresses; however, they are underpinned by an increased ATP demand. We found that when ATP demand increases to high levels, respiration cannot provide sufficient ATP, leading to onset of respirofermentative metabolism. Although stress-specific factors increase ATP demand for cellular growth under stressful conditions, increased ATP demand for cellular maintenance underpins a general stress response and is responsible for the onset of overflow metabolism.
酵母细胞工厂在用于燃料和化学品的工业生产时会遇到物理和化学胁迫。这些胁迫会降低生产力并增加生物过程成本。了解应激反应机制对于提高平台菌株的细胞稳健性至关重要。我们研究了酵母最常遇到的三种工业胁迫（乙醇、盐和温度），以确定在恒化器条件下消除特定生长速率依赖性变化时的一般和应激特异性反应机制。通过应用系统水平分析，我们发现大多数应激反应都集中在线粒体过程上。我们的分析表明，施加的胁迫之间应激特异性因素有所不同；然而，它们的基础是ATP需求增加。我们发现，当ATP需求增加到高水平时，呼吸作用无法提供足够的ATP，导致呼吸发酵代谢的开始。尽管应激特异性因素在应激条件下增加了细胞生长的ATP需求，但细胞维持所需的ATP需求增加是一般应激反应的基础，并导致溢流代谢的开始。
