title: A new physiological role for Pdr12p in Saccharomyces cerevisiae: export of aromatic and branched-chain organic acids produced in amino acid catabolism.
abstract: Saccharomyces cerevisiae can use a broad range of compounds as sole nitrogen source. Many amino acids, such as leucine, tyrosine, phenylalanine and methionine, are utilized through the Ehrlich pathway. The fusel acids and alcohols produced from this pathway, along with their derived esters, are important contributors to beer and wine flavor. It is unknown how these compounds are exported from the cell. Analysis of nitrogen-source-dependent transcript profiles via microarray analysis of glucose-limited, aerobic chemostat cultures revealed a common upregulation of PDR12 in cultures grown with leucine, methionine or phenylalanine as sole nitrogen source. PDR12 encodes an ABC transporter involved in weak-organic-acid resistance, which has hitherto been studied in the context of resistance to exogenous organic acids. The hypothesis that PDR12 is involved in export of natural products of amino acid catabolism was evaluated by analyzing the phenotype of null mutants in PDR12 or in WAR1, its positive transcriptional regulator. The hypersensitivity of the pdr12Delta and war1Delta strains for some of these compounds indicates that Pdr12p is involved in export of the fusel acids, but not the fusel alcohols derived from leucine, isoleucine, valine, phenylalanine and tryptophan.
authors.affiliation: Department of Biotechnology, Industrial Microbiology Section, Delft University of Technology, Delft, The Netherlands.
authors.forename: Lucie A
authors.initials: LA
authors.lastname: Hazelwood
authors.forename: Siew Leng
authors.initials: SL
authors.lastname: Tai
authors.forename: Viktor M
authors.initials: VM
authors.lastname: Boer
authors.forename: Johannes H
authors.initials: JH
authors.lastname: de Winde
authors.forename: Jack T
authors.initials: JT
authors.lastname: Pronk
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Daran
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism*; D002264:Carboxylic Acids / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D026901:Membrane Transport Proteins / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000596:Amino Acids; D002264:Carboxylic Acids; D026901:Membrane Transport Proteins; C472673:Pdr12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C472674:War1 protein, S cerevisiae