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Figure 8 - from "Mathematical modelling of industrial pilot-plant penicillin-G fed-batch fermentations"

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arrow_backarrow_forwardParameter Set, Initial and Operating Conditions for the Mathematical Model Employed TABLE 4 In fed-batch operation scheduled discharges were performed. As discharges were very fast (c. 1 min) they were treated as discrete instantaneous phenomena in model integration, halting integration at a discharge and resuming this after volume correction. The term F,,, was introduced in eqn (15) to account for evaporated water, since the cumulative amount lost is 20-30% of the initial culture broth.

Parameter Set, Initial and Operating Conditions for the Mathematical Model Employed TABLE 4 In fed-batch operation scheduled discharges were performed. As discharges were very fast (c. 1 min) they were treated as discrete instantaneous phenomena in model integration, halting integration at a discharge and resuming this after volume correction. The term F,,, was introduced in eqn (15) to account for evaporated water, since the cumulative amount lost is 20-30% of the initial culture broth.

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Fig. 1. Bioreactor system employed. A—motor; B—charge port; C—inspection window; D—agitator with two 6-blade disk turbines; E—air inlet; F—thermocouple sheath; G—bottom discharge; H—jacket inlet; I—baffle; J—jacket outlet; K—ring sparger,; L—holes for sensors (e.g. pH, O,, CO,).
Pilot-Scale Penicillin-G Fermentations Studied in the Present Work
Definition of the specific rates yu, 2 and o, in terms of simple empirical or semi-empirical functions of the state variables, completes the modelling. As a reference model for this study, the specific rates proposed by Bajpai and Reuss® were adopted. Here, a different formulation of these mass balance equations and chosen empirical expressions is proposed and shown to have an improved fit to the industrial fermentation conditions of this work. Penicillin fermentation can be envisaged as a reactive process in which biomass and penicillin are produced at the expense of substrates such as glucose (the most important carbon and energy source) and organic nitrogen compounds. Since the concentrations of biomass (X ), penicillin (P) and glucose (S) are routinely measured at the plant, they were chosen as process state variables together with broth volume (V) which varies in a fed-batch process. Dynamics of biomass growth, penicillin production and glucose consumption can then be described by a set of mass balances on these state variables (in eqn (4), broth density was assumed to be constant through the fermentation):
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Fig. 2. Averaged concentration profiles of biomass, penicillin (as Pen-GK) and glucose, for eight fermentation ( upper and lower bounds on state variable profiles), aver J.C. Menezes, S. S. Alves, J. M. Lemos, S. F. de Azevedo Tek ode See: gee ee Experimental penicillin concentration profiles were also sigmoidal, suggesting that a Monod-type model may be used (Fig. 2). However, Bajpai and Reuss® have proposed a mechanistic model for penicillin production based on a substrate inhibition law to account for glucose catabolite repression. Examining experimental (4) and n(S) profiles, broad, flat maxima were observed, which are not compatible with inhibition kinetics (as discussed later). Therefore, under the experimental conditions of this study, repression of penicillin production could not be identified. This is in agreement with data obtained by Revilla et al.2 and Dhanutirto et al.2? which showed repression was present for glucose concentrations above 5-10 gdm~3. As residual glucose concentrations vary from 0:5 to 1:0 g dm, the rate expression proposed by Bajpai and Reuss,® Fos oe” Peres Se Pe wee Pe Glucose concentration profiles (Fig. 2) showed the two regimes present in a fed-batch fermentation: a high substrate growth phase and a low substrate production phase. The Herbert—Pirt model, proposed by Bajpai and Reuss® to describe substrate consumption for growth, production and maintenance metabolism, has been retained:
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Fig. 4. Metabolised amounts of carbon substrates present in the fed-batch fermentation culture broth of P. chrysogenum (Q glucose; @ fructose; ™ amino-compounds; & lactic acid). ‘ig. 3. Variation in carbon substrates with time in a penicillin-G fed-batch fermentation (* amino-compounds; © glucose; A ructose; [1 lactic acid). Glucose measured with the Y27 enzymatic analyser; fructose and lactic acid by HPLC, and amino-compounds by Kjeldahl method.
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Sebastião Alves
Sebastião Alves
Mathematical modelling of industrial pilot-plant penicillin-G fed-batch fermentations

Abstract: Penicillin-G fermentation with industrial media in 1 m3 stirred tank bioreactors was studied. A model based on the Bajpai-Reuss model structure was developed. Under typical production conditions catabolite repression is nonidentifiable and extensive mycelium differentiation occurs. Thus, the original model was reformulated, neglecting glucose repression of penicillin production and including biomass autolysis. The multi-substrate nature of industrial media was critically analysed. By combining the two most important carbon substrates present, a simple and applicable model was obtained. Model predictions agreed well with experimental data and reproduced the general characteristics observed in the fermentations. The predictive power of the model was tested for fermentations with different sugar feed rate profiles and raw materials (corn-steep liquor and sugar syrup). Several aspects of parameter estimation and model development are discussed on the basis of direct experimental data inspection and a sensitivity analysis of model parameters.

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