Biosynthesis of Lysine from a-Ketoadipic Acid and oa-Aminoadipic Acid in Yeast

Studies of the nutrition of certain lysine requiring mold mutants indicate that L-a-aminoadipic acid (AAA) or a-ketoadipic acid (KAA) are precursors of lysine. For example, Mitchell and Houlahan (1948) found that certain lysine requiring mutants of Neurospora crassa would respond to either lysine or AAA, and Windsor (1951) subsequently demonstrated that f-C'4-a-aminoadipic acid was completely incorporated into lysine in one such mutant. Lysine requiring mutants of Ophiostoma (Bergstrom and Rottenberg, 1950) utilize either KAA or AAA for growth in lieu of lysine. The pathway of lysine biosynthesis in yeast has been studied by Strassman and Weinhouse (1953); from the manner in which acetate is incorporated into lysine of the proteins of Torulopsis utilis, a scheme compatible with the idea that KAA and AAA could be precursors of lysine in yeast was proposed for the origin of KAA from carbohydrate metabolism. Current efforts to produce L-lysine commercially either by chemical or biological means such that it might be economically feasible to fortify certain foodstuffs deficient in this amino acid with L-lysine (e.g., see Howe, 1957) prompted us to consider the possibility that microorganisms might be found having a high capacity to produce lysine when grown with adipic acid derivatives. After a brief screening program involving several hundred yeasts, molds, and bacteria, it became evident that many common yeasts, particularly certain strains of Saccharomyces and Torulopsis, have a marked capacity to convert KAA or AAA to lysine. Such lysine is found in the yeast cell but is apparently not bound to protein, as it is readily extracted from the cells with hot water; such yeasts may contain as much as 20 per cent of their dry weight as lysine. These findings have both practical and theoretical interest, for they suggest a possible means of producing lysine and lend strong support to an "adipic acid pathway" of lysine biosynthesis in yeast. A brief account of this work has appeared elsewhere (Broquist and Stiffey, 1959).