Accumulation of tricarboxylic acids related to lysine biosynthesis in a yeast mutant.

Accumulation of tricarboxylic acids related to lysine biosynthesis has been demonstrated in a yeast mutant, Ly,,, which requires lysine as a growth factor in synthetic medium but can substitute a-aminoadipic acid for the nutritional requirement of lysine. Both radioactive and nonradioactive intermediates have been isolated from the growth medium under appropriate conditions and have been identified chromatographically, chemically, and spectroscopically as homocitric, cis-homoaconitic, and homoisocitric acids. Homocitric acid is in equilibrium as the free acid and lactone following treatment with formic acid. These intermediates in the lysine pathway are not accumulated in the wild-type yeast. The mutant Ly,, does not accumulate a-ketoadipic acid, indicating that the biochemical block in this mutant corresponds to the biosynthetic step preceding ol-ketoadipic acid. Accumulation of these tricarboxylic acids in the culture medium of a lysine auxotroph provides additional evidence in support of their obligate intermediary role in lysine biosynthesis.