title: Regulation of carotenogenesis in the red yeast Xanthophyllomyces dendrorhous: the role of the transcriptional co-repressor complex Cyc8-Tup1 involved in catabolic repression.
abstract: The yeast Xanthophyllomyces dendrorhous produces carotenoids of commercial interest, including astaxanthin and β-carotene. Although carotenogenesis in this yeast and the expression profiles of the genes controlling this pathway are known, the mechanisms regulating this process remain poorly understood. Several studies have demonstrated that glucose represses carotenogenesis in X. dendrorhous, suggesting that this pathway could be regulated by catabolic repression. Catabolic repression is a highly conserved regulatory mechanism in eukaryotes and has been widely studied in Saccharomyces cerevisiae. Glucose-dependent repression is mainly observed at the transcriptional level and depends on the DNA-binding regulator Mig1, which recruits the co-repressor complex Cyc8-Tup1, which then represses the expression of target genes. In this work, we studied the regulation of carotenogenesis by catabolic repression in X. dendrorhous, focusing on the role of the co-repressor complex Cyc8-Tup1.
  
  
  
  The X. dendrorhous CYC8 and TUP1 genes were identified, and their functions were demonstrated by heterologous complementation in S. cerevisiae. In addition, cyc8-and tup1-mutant strains of X. dendrorhous were obtained, and both mutations were shown to prevent the glucose-dependent repression of carotenogenesis in X. dendrorhous, increasing the carotenoid production in both mutant strains. Furthermore, the effects of glucose on the transcript levels of genes involved in carotenogenesis differed between the mutant strains and wild-type X. dendrorhous, particularly for genes involved in the synthesis of carotenoid precursors, such as HMGR, idi and FPS. Additionally, transcriptomic analyses showed that cyc8-and tup1-mutations affected the expression of over 250 genes in X. dendrorhous.
  
  
  
  The CYC8 and TUP1 genes are functional in X. dendrorhous, and their gene products are involved in catabolic repression and carotenogenesis regulation. This study presents the first report involving the participation of Cyc8 and Tup1 in carotenogenesis regulation in yeast.
authors.affiliation: Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Ñuñoa, Santiago, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Córdova
authors.affiliation: Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Ñuñoa, Santiago, Chile.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Alcaíno
authors.affiliation: Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Ñuñoa, Santiago, Chile.
authors.forename: Natalia
authors.initials: N
authors.lastname: Bravo
authors.affiliation: Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Ñuñoa, Santiago, Chile.
authors.forename: Salvador
authors.initials: S
authors.lastname: Barahona
authors.affiliation: Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Ñuñoa, Santiago, Chile.
authors.forename: Dionisia
authors.initials: D
authors.lastname: Sepúlveda
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Departamento de Biología Molecular (UAM-CSIC), Universidad Autónoma Madrid, Campus de Cantoblanco, calle Nicolás Cabrera No 1, Cantoblanco, 28049, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Fernández-Lobato
authors.affiliation: Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Ñuñoa, Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Baeza
authors.affiliation: Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Ñuñoa, Santiago, Chile. vcifuentes@uchile.cl.
authors.forename: Víctor
authors.initials: V
authors.lastname: Cifuentes
mesh_terms: D001487:Basidiomycota / Q000235:genetics* / Q000378:metabolism*; D053898:Biosynthetic Pathways; D056970:Co-Repressor Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D060847:Metabolic Engineering / Q000379:methods; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D024341:Xanthophylls / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C065455:CYC8 protein, S cerevisiae; D056970:Co-Repressor Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D024341:Xanthophylls
keywords: Carotenogenesis; Catabolic repression; Cyc8–Tup1 co-repressor complex; Transcriptional regulation; Xanthophyllomyces dendrorhous