Control of enzyme synthesis in the lysine biosynthetic pathway of Saccharomyces cerevisiae

Abstract

Several enzymes of the lysine pathway of Saccharomyces cerevisiue were found to respond to an induction mechanism mediated by the product of gene LYSl4 in the presence of 2-aminoadipate semialdehyde, an intermediate of this pathway. This novel regulatory mechanism appears independent of the specific repression by lysine and of the general control of amino acid biosynthesis. Genes LYSI, LYS9 and LYSl4 have been cloned and their DNAs used to assay the corresponding messenger RNAs. The results suggest that the induction mechanism, as well as the specific and general regulations, operate at the transcriptional level.The synthesis of saccharopine dehydrogenase (glutamate-forming), previously shown to require the unlinked genes LYS9 and LYS14, is also affected by the induction mechanism. The leaky auxotrophic behaviour of lys14 mutants is explained by the low basal level of expression of LYS9, the structural gene of this enzyme, in the absence of induction by 2-aminoadipate semialdehyde.

A nonameric core sequence is required upstream of the LYS genes of Saccharomyces cerevisiae for Lys14p‐mediated activation and apparent repression by lysine

“…These two genes have been cloned and their mRNAs assayed by Northern (RNA) hybridization in different strains and under different growth conditions. The results of these experiments support the view that the Lys14p-dependent activation mechanism operates transcriptionally (Ramos et al, 1988). The regulatory gene LYS14 has been cloned and sequenced (Ramos et al, 1988;Feller et al, 1994).…”

“…The expression of the LYS genes is subjected to the general control of amino acid biosynthesis (Wolfner et al, 1975;Urrestarazu et al, 1985) and to a pathway-specific transcriptional activation mediated by Lys14p (Ramos et al, 1988). An intermediate of the pathway, ␣-aminoadipate semialdehyde, acts as coinducer for this activation mechanism (Ramos et al, 1988).…”

“…The expression of the LYS genes is subjected to the general control of amino acid biosynthesis (Wolfner et al, 1975;Urrestarazu et al, 1985) and to a pathway-specific transcriptional activation mediated by Lys14p (Ramos et al, 1988). An intermediate of the pathway, ␣-aminoadipate semialdehyde, acts as coinducer for this activation mechanism (Ramos et al, 1988). In addition, feedback inhibition by lysine of the first step of the pathway, catalysed by two homocitrate synthase isoenzymes (Tucci and Ceci, 1972;Ramos et al, 1996; G. Volckaert, personal communication; F. Ramos and E. Dubois, unpublished observation), modulates the metabolic flux through the pathway and, consequently, the production of ␣-aminoadipate semialdehyde.…”

Lysine degradation through the saccharopine pathway in mammals: involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse

“…The two final steps of the yeast pathway are catalysed by LOR and SDH encoded by separate genes, namely Lys1 and Lys9 [37,38]. We searched the GenBank looking for expressed sequence tags presenting similarity either to these yeast enzymes or to the maize LOR\SDH, whose gene had been cloned recently in our laboratory.…”

“…In yeast, Lys1 and Lys9 genes, encoding the enzymes LOR and SDH, are transcriptionally regulated by the LYS14 activator, which in turn is modulated by a saccharopine derivative (aminoadipate semialdehyde) [37,38]. In particular, high-lysine or high-protein diets seem to promote increases in LOR and SDH activities in the rat liver [40][41][42][43].…”