A structured model for penicillin production on mixed substrates

A structured kinetic model previously developed to describe the growth, dif ferentiation, and penicillin production of Penicillium chrysogenum has been enhanced and extended in order to apply it to a mixed carbon source fermen tation. The filamentous hyphae are divided into four distinct regions on th e basis of their activities and the physiological structure ( i.e., vacuola tion) of the hyphal compartments: viz., actively growing (mainly apical) re gions, non-growing or penicillin producing regions, vacuoles, and degenerat ed or metabolically inactive regions. A simple approach is taken to give qu antitative descriptions of hyphal extension, branch formation, vacuolation and differentiation. The fermentation medium contained glucose and lactose monohydrate as the main carbon sources. The source of the lactose was whey powder used in excess in the inoculum medium, whilst glucose was fed contin uously throughout the fermentation. Lactose, a disaccharide, is hydrolysed to two monosaccharides, glucose and galactose, when the residual glucose co ncentration in the medium drops to a very low level. The utilisation of glu cose and that of galactose following the hydrolysis of lactose were observe d to occur simultaneously. This allowed the assumption of simple lactose ut ilisation kinetics in which lactose hydrolysis could be considered as produ cing an equivalent amount of glucose. The model has been used for successfu l predictions of fed-batch penicillin fermentations using an industrial P. chrysogenum strain under different glucose feed rates. Quantitative informa tion on proportions of the hyphal regions was obtained from image analysis measurements and the parameters of the model were identified. When the gluc ose feed rate to the production culture was switched between a high and a l ow value, the model successfully predicted the dynamic changes of different iation and the resulting penicillin production caused by the variations in the nutrient conditions. The use of image analysis to characterise differen tiation as a basis for structured modelling of the penicillin fermentation appears to be very powerful, and such models have great potential for use i n process simulation and control of antibiotic fermentations. (C) 1998 Else vier Science S.A. All rights reserved.