title: Kinetic models in industrial biotechnology - Improving cell factory performance.
abstract: An increasing number of industrial bioprocesses capitalize on living cells by using them as cell factories that convert sugars into chemicals. These processes range from the production of bulk chemicals in yeasts and bacteria to the synthesis of therapeutic proteins in mammalian cell lines. One of the tools in the continuous search for improved performance of such production systems is the development and application of mathematical models. To be of value for industrial biotechnology, mathematical models should be able to assist in the rational design of cell factory properties or in the production processes in which they are utilized. Kinetic models are particularly suitable towards this end because they are capable of representing the complex biochemistry of cells in a more complete way compared to most other types of models. They can, at least in principle, be used to in detail understand, predict, and evaluate the effects of adding, removing, or modifying molecular components of a cell factory and for supporting the design of the bioreactor or fermentation process. However, several challenges still remain before kinetic modeling will reach the degree of maturity required for routine application in industry. Here we review the current status of kinetic cell factory modeling. Emphasis is on modeling methodology concepts, including model network structure, kinetic rate expressions, parameter estimation, optimization methods, identifiability analysis, model reduction, and model validation, but several applications of kinetic models for the improvement of cell factories are also discussed.
authors.affiliation: Fraunhofer-Chalmers Centre, Chalmers Science Park, SE-412 88 Göteborg, Sweden; Systems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden. Electronic address: joachim.almquist@fcc.chalmers.se.
authors.forename: Joachim
authors.initials: J
authors.lastname: Almquist
authors.affiliation: Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, SE-412 96 Göteborg, Sweden; Mathematical Sciences, University of Gothenburg, SE-412 96 Göteborg, Sweden.
authors.forename: Marija
authors.initials: M
authors.lastname: Cvijovic
authors.affiliation: Laboratory of Computational Systems Biotechnology, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland.
authors.forename: Vassily
authors.initials: V
authors.lastname: Hatzimanikatis
authors.affiliation: Systems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Fraunhofer-Chalmers Centre, Chalmers Science Park, SE-412 88 Göteborg, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Jirstrand
mesh_terms: D001709:Biotechnology; D007700:Kinetics; D060847:Metabolic Engineering; D008954:Models, Biological
keywords: Cell factory; Dynamic models; Industrial biotechnology; Kinetic models; Mathematical modeling; Parameter estimation