title: Identification of transcription factors perturbed by the synthesis of high levels of a foreign protein in yeast Saccharomyces cerevisiae.
abstract: For years, micro-organisms have been used for the industrial production of heterologous proteins. However, the production of foreign proteins causes undesirable problems for the host organism. The analysis of this phenomenon is desirable to improve the production of relevant proteins and so far no analysis of the effects of recombinant protein production on genetic regulation has been reported. In this work, network component analysis (NCA) was used to deduce transcription factor activities (TFAs) in a recombinant strain of Saccharomyces cerevisiae that produces a foreign protein, human superoxide dismutase (SOD) and compared the behavior of this yeast strain to the wild-type host to see the effect of the expression of the protein at the regulatory level. NCA identified a network of 817 genes regulated by 87 transcription factors (TFs). From the identified TFs, 45 show significant change in their activities at least in one of the three phases of diauxic growth (glucose, ethanol, and early stationary phase). The major effect of the expression of SOD on the activity of the TFs was observed in the early stationary phase with 34 of them perturbed in comparison with 12 on glucose and 20 on ethanol. These TFs cover the main functions of the cell, such as developmental processes, cell cycle, metabolism, and environmental response. Five of them are present in all growth phases: Hal9, Mac1, Oaf3, Stp1, and Urc2. In addition, TFA analysis corroborates the hypothesis that copper plays a key role as a stress factor and suggests that YJL206C, a TF with unknown function, could be related to Ace2, a cell cycle regulator.
authors.affiliation: Department of Chemical Engineering and Biotechnology, Institute for Cell Dynamics and Biotechnology: A Centre for Systems Biology, University of Chile, Santiago Plaza Ercilla 847, Santiago, Chile.
authors.forename: Carolina A
authors.initials: CA
authors.lastname: Contador
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Andrews
authors.forename: James C
authors.initials: JC
authors.lastname: Liao
authors.forename: Juan A
authors.initials: JA
authors.lastname: Asenjo
mesh_terms: D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology; D008962:Models, Theoretical; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D013482:Superoxide Dismutase