title: Natural Diversity in Pentose Fermentation Is Explained by Variations in Histone Deacetylases.
abstract: The extent to which carbon flux is directed toward fermentation versus respiration differs between cell types and environmental conditions. Understanding the basic cellular processes governing carbon flux is challenged by the complexity of the metabolic and regulatory networks. To reveal the genetic basis for natural diversity in channeling carbon flux, we applied quantitative trait loci analysis by phenotyping and genotyping hundreds of individual F2 segregants of budding yeast that differ in their capacity to ferment the pentose sugar xylulose. Causal alleles were mapped to the RXT3 and PHO23 genes, two components of the large Rpd3 histone deacetylation complex. We show that these allelic variants modulate the expression of SNF1/AMPK-dependent respiratory genes. Our results suggest that over close evolutionary distances, diversification of carbon flow is driven by changes in global regulators, rather than adaptation of specific metabolic nodes. Such regulators may improve the ability to direct metabolic fluxes for biotechnological applications.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Tamari
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: naama.barkai@weizmann.ac.il.
authors.forename: Naama
authors.initials: N
authors.lastname: Barkai
mesh_terms: D000595:Amino Acid Sequence; D061249:Batch Cell Culture Techniques; D001665:Binding Sites; D002244:Carbon / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010429:Pentoses / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D040641:Quantitative Trait Loci; D012045:Regulatory Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D009687:Nuclear Proteins; D010429:Pentoses; C432409:Pho23 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002244:Carbon; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases