The role of pipecolic acid in the biosynthesis of lysine was investigated in Rhodotorula glutinis , an aerobic red yeast. Supplementation of pipecolic acid in the minimal medium supported the growth of mutants lys2, lys3 , and lys5 ; α-aminoadipic acid supported the growth of lys5 ; but neither α-aminoadipic acid nor pipecolic acid supported the growth of mutants MNNG42 and MNNG37. During the growth of the appropriate mutants, pipecolic acid was removed from the growth medium and the intracellular pool. In tracer experiments, radioactivity from [ 14 C]pipecolic acid was selectively incorporated into the cellular lysine of lys5 and the wild-type strain. l -Pipecolic acid-dependent enzyme activity did not require any cofactor and was inhibited by mercuric chloride and potassium cyanide. This activity was present in the wild-type strain and all of the mutants tested and was repressed in mutant lys5 when grown in the presence of higher concentration of lysine. The reaction product of pipecolic acid was converted to saccharopine by lys5 enzyme in the presence of glutamate and reduced nicotin-amide adenine dinucleotide phosphate. Mutant MNNG37 lacked the saccharopine dehydrogenase activity, indicating that this step is involved in the conversion of α-aminoadipic acid and pipecolic acid to lysine. Mutants MNNG37 and MNNG42 accumulated a p -dimethylaminobenzaldehyde-reacting product in the culture supernatant and in the intracellular pool. Chromatographic properties of the p -dimethylaminobenzaldehyde adduct and that of the pipecolic acid-dependent reaction product were similar. The reaction product and the accumulation product were characterized on the basis of mass and absorption spectra as α-aminoadipic-semialdehyde, which in solution remains in equilibrium with Δ 1 -piperideine-6-carboxylic acid. Since α-aminoadipic-semialdehyde is a known intermediate of the α-aminoadipic acid pathway for the biosynthesis of lysine, it is concluded that pipecolic acid is converted to lysine in R. glutinis via α-aminoadipic-semialdehyde and saccharopine.

Kinzel, J. J., & Bhattacharjee, J. K. (1979). Role of Pipecolic Acid in the Biosynthesis of Lysine in Rhodotorula glutinis. Journal of Bacteriology, 138(2), 410–417.