Mathematical modeling of proteinase A overproduction by Saccharomyces cerevisiae.
A simple, structured model was developed to describe the growth and product formation behavior of two recombinant strains of Saccharomyces cerevisiae (JG176 and JG180), both overproducing extracellular proteinase A. The model parameters were estimated to data from continuous fermentations obtained at steady-state conditions. Model predictions show good agreement with experimental data obtained by batch fermentations. The two concerned organisms are distinguished from each other by the type of promoter on the plasmids controlling the proteinase A expression. The proteinase A transcription is controlled by the natural proteinase A promoter in JG176 and by a tpi promoter in JG180. By means of experiments and simulations, the extracellular product formation from the two strains with different promoter systems was compared in batch and continuous fermentations. The results showed that the proteinase A formation kinetic from JG176 was a combination of growth and nongrowth associated (production in the stationary growth phase), whereas the proteinase A formation from JG180 was truly growth associated (production in the exponential growth phase). In both batch and continuous cultivations JG176 gave the highest product concentrations and volumetric productivities.
Grøn
S
S
Department of Biotechnology, Technical University of Denmark, Lyngby, Denmark.
Jochumsen
K V
KV
Biedermann
K
K
Emborg
C
C
D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D003001:Cloning, Molecular / Q000379:methods*; D005285:Fermentation; D017353:Gene Deletion; D005800:Genes, Fungal; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D014305:Triose-Phosphate Isomerase / Q000235:genetics
D011994:Recombinant Proteins; D016282:Aspartic Acid Endopeptidases; C022442:aspergillopepsin II; D014305:Triose-Phosphate Isomerase