Homocitric Acid Accumulation by a Lysine-requiring Yeast Mutant

From the ¹ From the Department of Microbiology, Research Laboratories, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

The accumulation of ß-carboxy-ß-hydroxyadipic acid (homocitric acid) in the culture medium of the lysine-requiring yeast mutant, Ly₄, grown on limiting amounts of lysine, has been demonstrated. Identity of the biologically formed acid with synthetic homocitric acid was established by comparison of infrared spectra, R_f values from paper chromatograms, optical rotations, and melting points. Radioactively labeled homocitric acid was obtained from the mutant grown on uniformly labeled ¹⁴C-glucose, as well as by incubation of a cell-free extract of the organism with 1-¹⁴C-acetate and -ketoglutarate. Radioactive lysine was obtained from the hydrolysate of wild-type yeast grown in the presence of ¹⁴C-labeled homocitrate. The excretion of homocitric acid by a lysine-requiring yeast mutant and its conversion into lysine convincingly establish the biosynthesis of lysine in yeast via the previously proposed scheme involving homologues of the citric acid cycle.

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