- Metabolic phenotypes of Saccharomyces cerevisiae mutants with altered trehalose-6-phosphate dynamics
- Biochemical Journal
- Volume | Issue number
- 454 | 2
- Pages (from-to)
- Document type
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
In Saccharomyces cerevisiae, synthesis of trehalose-6-phosphate (T6P) is essential for growth on most fermentable carbon sources. The metabolic response to glucose was analysed in mutants with different capacity to accumulate T6P. A mutant carrying a deletion in the T6P synthase encoding gene, TPS1, which had no measurable T6P exhibited impaired ethanol production, showed diminished plasma membrane H+-ATPase activation, and became rapidly depleted of nearly all adenine nucleotides which were irreversibly converted to inosine. Deletion of the AMP deaminase encoding gene, AMD1, in the tps1 strain prevented inosine formation but did not rescue energy balance or growth on glucose. Neither the 90 % reduced T6P content observed in a tps1 mutant expressing the Tps1 protein from Yarrowia lipolytica, nor the hyper-accumulation of T6P in the tps2 mutant had significant effects on fermentation rates, growth on fermentable carbon sources, or plasma membrane H+-ATPase activation. However, intracellular metabolite dynamics and pH homeostasis were strongly affected by changes of T6P concentrations. Hyper-accumulation of T6P in the tps2 mutant caused an increase of cytosolic pH and strongly reduced growth rates on non-fermentable carbon sources emphasizing the crucial role of the trehalose pathway in the regulation of respiratory and fermentative metabolism.
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