Applications of modelling for bioprocess design and control in industrial production

The on-line measurement of the relevant parameters and the control conception for three production processes for fine chemicals by fermentation and biotransformation at the 15 m³ scale were developed. The models describe the bioprocesses which successfully result in fully automated manufacturing steps. Modelling also proved to be a valuable tool for a better insight into biochemical fundamentals of the processes. Moreover, proper use of data logging, modelling and process control was important for quality, since two processes were controlled on-line and quality relevant deviations were registered early. Finally, combining modelling with simulation, we could drastically reduce both development time and cost.List of Symbols F l/h flux - V l volume - U ₀ g/l nicotinonitrile concentration influx - U g/l actual nicotinonitrile concentration - q _ug/gh specific educt (=nicotinonitrile) transformation rate - x g/l biocatalyst concentration - p ₀ g/l nicotinamide concentration influx - p g/l actual nicotinamide concentration - q _pg/gh specific product (=nicotinamide) formation rate - k parameter loss of activity - q _{u, max}g/gh max. specific educt transformation rate - K _ug/l saturation constant for nicotinonitrile - K _ig/l inhibition constant for nicotinonitrile - K _iig/l inhibition constant for nicotinamide - MW _Ag/mol molecular weight for nicotinonitrile - MW _Bg/mol molecular weight for nicotinamide - NS Nicotinic acid - 6-HNS 6-Hydroxynicotinic acid - r _{NS, 6HNS} g/lh 6-HNS production rate - r _{6HNS, X} g/lh biomass production rate - r _{NS, 6HNS, max} g/lh max. 6-HNS production rate - S _NS g/l actual NS concentration - K _{S, NS} g/l saturation constant for NS - K _{i, 6HNS} g/l inhibition constant for 6-HNS - K _o2 g/l saturation constant for oxygen - r _{6HNS, X, max} g/lh max. biomass production rate - S _6HNS g/l actual 6-HNS concentration - K _{ii, NS} g/l inhibition constant for NS - RQ mol/mol respiration quotient - S _xylg/l actual xylene concentration - K _{i, xyl}g/ inhibition constant for xylene - K _{i, DMPY}g/ inhibition constant for 2,5-dimethylpyrazine - r _Xg/lh biomass production rate - r _{X, max}g/lh max. biomass production rate - K _{s, xyl}g/l saturation constant for xylene - S _DMPYg/l actual concentration of DMPY - K _{i, MPCA}g/ inhibition constant for MPCA - K _O2g/ saturation constant for oxygen - S _MPCAg/l actual MPCA concentration - S _O2g/l actual oxygen concentration - r _MPCAg/lh MPCA production rate - r _{MPCA, max}g/lh max. MPCA production rate - k _lgl inhibition constant for the intermediates - k _{s, DMPY}gl saturation constant for DMPY