Multivalent Repression of Isoleucine- Valine Biosynthesis in Saccharomyces Cerevisiae

Regulation of the biosynthesis of four of the five enzymes of the isoleucine-valine pathway was studied in Saccharomyces cerevisiae. A method is described for limiting the growth of a leucine auxotroph by using valine as a competitor for the permease. Limitation for isoleucine and valine was accomplished by the use of peptides containing these amino acids conjugated with glycine as nutritional supplements for auxotrophs. The enzymes were repressed on synthetic medium containing isoleucine, valine, and leucine, as well as on broth supplemented with these amino acids. Limitation for any of the three branched-chain amino acids led to derepression of the isoleucine-valine biosynthetic pathway. Maximal derepression ranged from 3-fold for threonine deaminase to approximately 10-fold for acetohydroxyacid synthase. (Two of the enzymes, acetohydroxyacid synthase and dihydroxyacid dehydrase, may be controlled by a mechanism different from that regulating threonine deaminase.) Possible molecular mechanisms for multivalent repression are discussed.