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Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-03-06 , DOI: 10.1021/acssynbio.9b00376 Caroline Kampmeyer 1 , Jens V Johansen 2 , Christian Holmberg 1 , Magnus Karlson 3 , Sarah K Gersing 1 , Heloisa N Bordallo 4 , Birthe B Kragelund 1, 5 , Mathilde H Lerche 3 , Isabelle Jourdain 6 , Jakob R Winther 1 , Rasmus Hartmann-Petersen 1, 5
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-03-06 , DOI: 10.1021/acssynbio.9b00376 Caroline Kampmeyer 1 , Jens V Johansen 2 , Christian Holmberg 1 , Magnus Karlson 3 , Sarah K Gersing 1 , Heloisa N Bordallo 4 , Birthe B Kragelund 1, 5 , Mathilde H Lerche 3 , Isabelle Jourdain 6 , Jakob R Winther 1 , Rasmus Hartmann-Petersen 1, 5
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Life is completely dependent on water. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D2O) and investigated the biological effects by a wide range of techniques, using Schizosaccharomyces pombe as model organism. We show that high concentrations of D2O lead to altered glucose metabolism and growth retardation. After prolonged incubation in D2O, cells displayed gross morphological changes, thickened cell walls, and aberrant cytoskeletal organization. By transcriptomics and genetic screens, we show that the solvent replacement activates two signaling pathways: (1) the heat-shock response pathway and (2) the cell integrity pathway. Although the heat-shock response system upregulates various chaperones and other stress-relieving enzymes, we find that the activation of this pathway does not offer any fitness advantage to the cells under the solvent-replaced conditions. However, limiting the D2O-triggered activation of the cell integrity pathway allows cell growth when H2O is completely replaced with D2O. The isolated D2O-tolerant strains may aid biological production of deuterated biomolecules.
中文翻译：
单一信号通路中的突变可使细胞在重水中生长。
生活完全取决于水。为了分析水在生物学中的溶剂作用，我们用重水（D2O）代替了水，并使用粟酒裂殖酵母（Schizosaccharomyces pombe）作为模型生物，通过多种技术研究了生物学效应。我们表明，高浓度的D2O导致改变的葡萄糖代谢和生长迟缓。在D2O中长时间孵育后，细胞显示出总体形态变化，细胞壁增厚和异常的细胞骨架组织。通过转录组学和遗传筛选，我们表明溶剂替代激活了两个信号传导途径：（1）热休克反应途径和（2）细胞完整性途径。尽管热休克反应系统会上调各种分子伴侣和其他缓解压力的酶，我们发现在溶剂替代条件下，该途径的激活不会为细胞提供任何适应性优势。但是，当H2O完全被D2O取代时，限制D2O触发的细胞完整性途径的激活将允许细胞生长。分离的D2O耐受菌株可以帮助氘化生物分子的生物生产。
更新日期：2020-04-23
中文翻译：
单一信号通路中的突变可使细胞在重水中生长。
生活完全取决于水。为了分析水在生物学中的溶剂作用，我们用重水（D2O）代替了水，并使用粟酒裂殖酵母（Schizosaccharomyces pombe）作为模型生物，通过多种技术研究了生物学效应。我们表明，高浓度的D2O导致改变的葡萄糖代谢和生长迟缓。在D2O中长时间孵育后，细胞显示出总体形态变化，细胞壁增厚和异常的细胞骨架组织。通过转录组学和遗传筛选，我们表明溶剂替代激活了两个信号传导途径：（1）热休克反应途径和（2）细胞完整性途径。尽管热休克反应系统会上调各种分子伴侣和其他缓解压力的酶，我们发现在溶剂替代条件下，该途径的激活不会为细胞提供任何适应性优势。但是，当H2O完全被D2O取代时，限制D2O触发的细胞完整性途径的激活将允许细胞生长。分离的D2O耐受菌株可以帮助氘化生物分子的生物生产。
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