α-Aminoadipate Pathway for the Biosynthesis of Lysine in Lower Eukaryotes

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Abstract
Bacteria and green plants use the diaminopimelate pathway for the biosynthesis of the essential amino acid, lysine; however, yeast and other higher fungi use the alpha-aminoadipate (AA) pathway. The AA pathway has been investigated in detail biochemically, genetically, and in terms of regulatory mechanisms in the baker's yeast Saccharomyces cerevisiae. The genetic analysis of lysine auxotrophs of S. cerevisiae revealed that there are more than 12 lysine genes for 8 enzyme-catalyzed steps. Lysine genes are not linked to each other and seven of the genes are mapped on six different linkage groups (chromosomes). The gene-enzyme relationships have been determined for ten of the lysine loci which include two unlinked gene functions required for each of AA reductase (LYS2 and LYS5) and Saccharopine reductase (LYS9 and LYS14). Five of the lysine enzymes are localized in mitochondria and three in cytosol. The lysine pathway of S. cerevisiae is regulated by feedback inhibition and end product repression. Two, and possibly three, of the enzymes exhibit general control of amino acid biosynthesis and at least five of the enzymes coded for, by unlinked genes, are simultaneously depressed in a regulatory (repressor) gene-mutant.