Genetically structured modeling of protein production in filamentous fungi.
A general framework for a genetically structured model is presented. The framework allows description of the interactions in a system of regulatory and structural genes. The model assumes equilibrium kinetics for the binding of regulatory proteins to the promoter regions of the genes and includes the possible activation of proteins following their synthesis. The model is evaluated by simulating the alcA-expression (alcohol dehydrogenase I) in Aspergillus nidulans which is an inducible system subject to glucose repression. The intracellular enzyme levels in strains with different regulatory mutations are simulated during various growth conditions. The model gives a good description of the experimental data with changes in only a few parameter values which have a mechanistic interpretation.
Agger
T
T
Center for Process Biotechnology, Department of Biotechnology, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Nielsen
J
J
D000426:Alcohol Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics; D001709:Biotechnology; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis*; D005658:Fungi / Q000235:genetics* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008954:Models, Biological; D009154:Mutation; D011485:Protein Binding; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D005656:Fungal Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D000426:Alcohol Dehydrogenase; D012321:DNA-Directed RNA Polymerases