title: Application of model-predictive control based on artificial neural networks to optimize the fed-batch process for riboflavin production.
abstract: The fed-batch process for commercial production of riboflavin (vitamin B2) was optimized on-line using model-predictive control based on artificial neural networks (ANNs). The information required for process models was extracted from both historical data and heuristic rules. After each cultivation the process model was readapted off-line to include the most recent process data. The control signal (feed rate), however, was optimized on-line at each sampling interval. An optimizer simulated variations in the control signal and assessed the forecasted model outputs according to an objective function. The optimum feed profile for increasing the product yield (YB2/S) and the amount of riboflavin at the time of harvesting was adjusted continuously and applied to the process. In contrast to the control by set-point profiles, the novel ANN-control is able to react on-line to variations in the process and also to incorporate the new process information continuously. As a result, both the total amount of riboflavin produced and the product yield increased systematically by more than 10% and the reproducibility of seven subsequently optimized batches was enhanced.
authors.affiliation: F Hoffmiann-La Roche Ltd, Vitamin Research-Biotechnology, Basel, Switzerland. k.kovar@hswzfh.ch
authors.forename: K
authors.initials: K
authors.lastname: Kovárová-Kovar
authors.forename: S
authors.initials: S
authors.lastname: Gehlen
authors.forename: A
authors.initials: A
authors.lastname: Kunze
authors.forename: T
authors.initials: T
authors.lastname: Keller
authors.forename: R V
authors.initials: RV
authors.lastname: Däniken
authors.forename: M
authors.initials: M
authors.lastname: Kolb
authors.forename: A P
authors.initials: AP
authors.lastname: van Loon
mesh_terms: D000465:Algorithms; D001412:Bacillus subtilis / Q000254:growth & development / Q000378:metabolism; D018533:Biomass; D019149:Bioreactors; D002245:Carbon Dioxide / Q000378:metabolism; D003198:Computer Simulation; D005947:Glucose / Q000378:metabolism; D007700:Kinetics; D016571:Neural Networks, Computer; D009584:Nitrogen / Q000008:administration & dosage; D012256:Riboflavin / Q000096:biosynthesis*
chemical_list: D002245:Carbon Dioxide; D005947:Glucose; D009584:Nitrogen; D012256:Riboflavin