Abstract
Uptake of poor nitrogen sources such as branched-chain amino acids is repressed in the presence of high-quality nitrogen sources such as NH4+ and glutamate (Glu), which is called nitrogen catabolite repression. Amino acid auxotrophic mutants of the fission yeast Schizosaccharomyces pombe were unable to grow on minimal medium containing NH4Cl or Glu even when adequate amounts of required amino acids were supplied. However, growth of these mutant cells was recovered in the vicinity of colonies of the prototrophic strain, suggesting that the prototrophic cells secrete some substances that can restore uptake of amino acids by an unknown mechanism. We identified the novel fatty acids, 10(R)-acetoxy-8(Z)-octadecenoic acid and 10(R)-hydroxy-8(Z)-octadecenoic acid, as secreted active substances, referred to as Nitrogen Signaling Factors (NSFs). Synthetic NSFs were also able to shift nitrogen source utilization from high-quality to poor nitrogen sources to allow adaptive growth of the fission yeast amino acid auxotrophic mutants in the presence of high-quality nitrogen sources. Finally, we demonstrated that the Agp3 amino acid transporter was involved in the adaptive growth. The data highlight a novel intra-species communication system for adaptation to environmental nutritional conditions in fission yeast.
Highlights
Plates were incubated at 30 °C for the indicated periods. (b) Activity of the supernatant of the prototrophic fission yeast strain that promotes adaptive growth of the eca39Δ cells
We identified two structurally novel compounds, 10(R)-acetoxy-8(Z)-octadecenoic acid ((R)-1) and 10(R)-hydroxy-8(Z)-octadecenoic acid ((R)-2), as Nitrogen Signaling Factors (NSFs), secreted from fission yeast
Compounds were dissolved in 50% MeOH, and a 2-fold dilution series of the compounds was prepared with a starting concentration of 2.5 × 104 ng mL−1 or 5.0 × 104 ng mL−1 to examine activity
Summary
Plates were incubated at 30 °C for the indicated periods. (b) Activity of the supernatant of the prototrophic fission yeast strain that promotes adaptive growth of the eca39Δ cells. We observed that the Leu auxotrophic mutant leu[1] grew adaptively near other strains on media containing Leu and excess NH4+, suggesting that the growth defects of eca39Δ and leu[1] mutants were due to inhibition of uptake of required amino acids in the presence of high-quality nitrogen sources[3]. These observations raise the possibility that fission yeast cells secrete one or more diffusible, species-specific, signaling molecules that trigger an adaptive metabolic shift to utilization of branched-chain amino acids as nitrogen sources, allowing the growth of amino acid auxotrophic mutants[3]
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