Expression of GAL genes in a mutant strain of Saccharomyces cerevisiae lacking GAL80: quantitative model and experimental verification.
The regulatory network of GAL genes is a model system for the production of foreign proteins. A mathematical model based on steady state was developed for the expression of GAL (galactosidase) genes in a mutant strain of Saccharomyces cerevisiae lacking GAL80. The transcriptional and translational responses of the GAL switch were predicted at various steady-state glucose concentrations. The model predicted ultrasensitive transcriptional response with a Hill coefficient ( h ) of 1.9 and 3.2 for genes with one and two binding sites respectively. Further, a lesser degree of ultrasensitivity was predicted for translational response with an h value of 1.3 for genes with one binding site and 2.1 for genes with two binding sites. The ultrasensitivity was due to dimerization of regulatory protein Gal4p and co-operative binding of Gal4p to DNA. The steady-state predictions were experimentally verified through measurements of alpha-galactosidase (for one binding site) and beta-galactosidase (for two binding sites). The steady state model was further extended to represent the dynamic expression profile and the same was verified experimentally. The growth phase and the synthesis of foreign protein could be distinctly separated using a mutant strain of Saccharomyces cerevisiae (baker's yeast).
Verma
Malkhey
M
Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Bhat
Paike Jayadeva
PJ
Venkatesh
K V
KV
D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D005690:Galactose / Q000235:genetics / Q000378:metabolism; D005696:Galactosidases / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D014176:Protein Biosynthesis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology
C055002:GAL80 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA; D005696:Galactosidases; D005947:Glucose; D005690:Galactose