title: Essential role of one-carbon metabolism and Gcn4p and Bas1p transcriptional regulators during adaptation to anaerobic growth of Saccharomyces cerevisiae.
abstract: The transcriptional activator Gcn4p is considered the master regulator of amino acid metabolism in Saccharomyces cerevisiae and is required for the transcriptional response to amino acid starvation. Here it is shown that Gcn4p plays a previously undescribed role in regulating adaptation to anaerobic growth. A gcn4 mutant exhibited a highly extended lag phase after a shift to anaerobiosis that was the result of l-serine depletion. In addition, the one-carbon metabolism and purine biosynthesis transcriptional regulator Bas1p were strictly required for anaerobic growth on minimal medium, and this was similarly due to l-serine limitation in bas1 mutants. The induction of one-carbon metabolism during anaerobiosis is needed to increase the supply of l-serine from the glycine and threonine pathways. Using a number of experimental approaches, we demonstrate that these transcription regulators play vital roles in regulating l-serine biosynthesis in the face of increased demand during adaptation to anaerobiosis. This increased l-serine requirement is most likely due to anaerobic remodeling of the cell wall, involving de novo synthesis of a large number of very serine-rich mannoproteins and an increase in the total serine content of the cell wall. During anaerobic starvation for l-serine, this essential amino acid is preferentially directed to the cell wall, indicating the existence of a regulatory mechanism to balance competing cellular demands.
authors.affiliation: School of Biomedical and Health Sciences, University of Western Sydney, Penrith, New South Wales DC 1791, Australia.
authors.forename: Bonny M
authors.initials: BM
authors.lastname: Tsoi
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Beckhouse
authors.forename: Cristy L
authors.initials: CL
authors.lastname: Gelling
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Joyce
authors.initials: J
authors.lastname: Chiu
authors.forename: Abraham M
authors.initials: AM
authors.lastname: Tsoi
authors.forename: Lars
authors.initials: L
authors.lastname: Lauterbach
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rogers
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Higgins
authors.forename: Ian W
authors.initials: IW
authors.lastname: Dawes
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors; D049109:Cell Proliferation; D002473:Cell Wall; D004268:DNA-Binding Proteins / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D005838:Genotype; D005998:Glycine / Q000737:chemistry; D008954:Models, Biological; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D012694:Serine / Q000737:chemistry; D013347:Subcellular Fractions; D013912:Threonine / Q000737:chemistry; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: C061767:BAS1 protein, S cerevisiae; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C501391:GCN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D013912:Threonine; D012694:Serine; D005998:Glycine