Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water

Life is completely dependent on water. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D 2 O) and investigated the biological effects by a wide range of techniques, using Schizosaccharomyces pombe as model organism. We show that high concentrations of D 2 O lead to altered glucose metabolism and growth retardation. After prolonged incubation in D 2 O, 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 D 2 O-triggered activation of the cell integrity pathway allows cell growth when H 2 O is completely replaced with D 2 O. The isolated D 2 O-tolerant strains may aid biological production of deuterated biomolecules.