METABOLISM OF SULFUR AMINO-ACIDS IN SACCHAROMYCES-CEREVISIAE

Sulfur amino acid biosynthesis in Saccharomyces cerevisiae involves a large number of enzymes required for the de novo biosynthesis of methi onine and cysteine and the recycling of organic sulfur metabolites. Th is review summarizes the details of these processes and analyzes the m olecular data which have been acquired in this metabolic area. Sulfur biochemistry appears not to be unique through terrestrial life, and S. cerevisiae is one of the species of sulfate-assimilatory organisms po ssessing a larger set of enzymes for sulfur metabolism. The review als o deals with several enzyme deficiencies that lead to a nutritional re quirement for organic sulfur; although they do not correspond to defec ts within the biosynthetic pathway In S. cerevisiae, the sulfur amino acid biosynthetic pathway is tightly controlled: in response to an inc rease in the amount of intracellular S-adenosylmethionine (AdoMet), tr anscription of the coregulated genes is turned off. The second part of the review is devoted to the molecular mechanisms underlying this reg ulation. The coordinated response to AdoMet requires two cis-acting pr omoter elements. One centers on the sequence TCACGTG, which also const itutes a component of all S. cerevisiae centromeres. Situated upstream of the sulfur genes, this element is the binding site of a transcript ion activation complex consisting of a basic helix-loop-helix factor C bf1p, and two basic leucine zipper factors, Met4p and Met28p. Molecula r studies have unraveled the specific functions for each subunit of th e Cbf1p-Met4p-Met28p complex as well as the modalities of its assembly on the DNA. The Cbf1p-Met4p-Met28p complex contains only one transcri ption activation module, the Met4p subunit. Detailed mutational analys is of Met4p has elucidated its functional organization. In addition to its activation and bZIP domains, Met4p contains two regulatory domain s, called the inhibitory region and the auxiliary domain. When the lev el of intracellular AdoMet increases, the transcription activation fun ction of Met4 is prevented by Met30p, which binds to the Met4 inhibito ry region. In addition to the Cbf1p-Met4p-Met28p complex, transcriptio nal regulation involves two zinc finger-containing proteins, Met31p an d Met32p. The AdoMet-mediated control of the sulfur amino acid pathway illustrates the molecular strategies used by eucaryotic cells to coup le gene expression to metabolic changes.