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Abstract

A kinetic model to describe lovastatin biosynthesis by Aspergillus terreus ATCC 20542 in a batch culture with the simultaneous use of lactose and glycerol as carbon sources was developed. In order to do this the kinetics of the process was first studied. Then, the model consisting of five ordinary differential equations to balance lactose, glycerol, organic nitrogen, lovastatin and biomass was proposed. A set of batch experiments with a varying lactose to glycerol ratio was used to finally establish the form of this model and find its parameters. The parameters were either directly determined from the experimental data (maximum biomass specific growth rate, yield coefficients) or identified with the use of the optimisation software. In the next step the model was verified with the use of the independent sets of data obtained from the bioreactor cultivations. In the end the parameters of the model were thoroughly discussed with regard to their biological sense. The fit of the model to the experimental data proved to be satisfactory and gave a new insight to develop various strategies of cultivation of A. terreus with the use of two substrates.
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Abstract

Biosynthesis of lovastatin (a polyketide metabolite of Aspergillus terreus) in bioreactors of different working volume was studied to indicate how the change of scale of the process influences the formation of this metabolite. The experiments conducted in shake flasks of 150 ml working volume allowed to obtain lovastatin titres at the level of 87.5 mg LOV l-1, when two carbon sources, namely lactose and glycerol were used. The application of the same components in a large stirred-tank bioreactor of 5.3-litre working volume caused a decrease of lovastatin production by 87% compared to the shake flask culture. The deficiency of nitrogen in this bioreactor did not favour the formation of lovastatin, in contrast to the small bioreactor of 1.95-litre working volume, in which lovastatin titres comparable to those in the shake flasks could be achieved, when organic nitrogen concentration was two-fold decreased. When the control of pH and/or pO2 was used simultaneously, an increase in lovastatin production was observed in the bioreactors. However, these results were still slightly lower than lovastatin titres obtained in the shake flasks.
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