The regulation of leucine biosynthesis in enteric bacteria will be further investigated, with emphasis on the role of the first specific enzyme of the pathway, alpha-isoprophylmalate synthase. The structure-function relationship of this enzyme will be further analyzed, using feedback-resistant and feedback-hypersensitive forms of the enzyme. Also, the possible role of alpha-isoprophylmalate synthase in controlling gene expression will be studied. Leucine pathway regulation will also be studied in yeast, in order to compare the bacterial system with that of a more highly developed, eucaryotic organism and to establish evolutionary changes that might have occurred.