GNPS - Fission yeast metabolome dynamics during phosphate starvation and replenishment

Inorganic phosphate is an essential nutrient acquired by cells from their environment and assimilated into myriad intracellular metabolites and macromolecules. Here we characterize the metabolic responses of fission yeast to a 24-h interval of phosphate starvation, during which cells enter a state of G0 quiescence. Time-resolved profiling revealed that many key phosphometabolites were progressively depleted, including: (i) NTPs, NDPs, and dNTPs; (ii) coenzyme A, NAD+, NADP+, NADH, and ADP-ribose; (iii) glycolysis pathway intermediates upstream of pyruvate; (iv) pentose phosphate pathway intermediates from 6-phosphogluconate to sedoheptulose-7-phosphate; (v) nucleotide sugars GDP-glucose/mannose, UDP-glucose/galactose, and UDP-GalNAc/GluNAc; and (vi) phospholipid precursors glycerol-3-phosphate, CDP-choline, and glycerophosphocholine. By contrast, early Krebs cycle intermediates accumulated during phosphate starvation. Other metabolic changes included: (i) interdiction of de novo pyrimidine synthesis; (ii) depletion of S-adenosylmethionine and S-adenosylhomocysteine; (iii) transient accumulation of polyamine biosynthetic intermediates putrescine, S-adenosylmethioninamine and 5-methylthioadenosine; (iv) accumulation of betaine (correlating with an increase in expression of atd1 mRNA encoding aldehyde dehydrogenase); and (v) depletion of aminoadipate pathway intermediates 2-oxoadipate, 2-aminoadipate and saccharopine. Replenishing phosphate after 24 h of starvation resulted in restoration of the metabolite levels to similar levels as non-starved controls (over 2 to 12 h) as cells exited quiescence and resumed growth.