higher compared to that in submerged fermentation [91]. Although there was
no increase in the total alkaloid content for Claviceps purpurea, the content of
ergonovine and ergotamine was higher, which is important from the commercial point of view. Further work [92] with Claviceps purpurea 1029c involving impregnation of the inert solid support, sugar cane pith bagasse, with
16 different combinations of the liquid nutrient medium such as rye meal or
sucrose as the carbon source, ammonium sulphate, urea, and ammonium
oxalate as the nitrogen source(s), other nutrients, namely potassium dihydrogen phosphate, magnesium sulphate, calcium nitrate, citric acid, and the amino
acids valine, proline, tryptophan, and Tween 80 showed that there was a
significant change in the alkaloid spectra and the authors suggested the possibility of achieving tailor-made spectra of ergot alkaloids, economically. Use of
different solid substrates also resulted in major changes in the spectra of
alkaloids produced. Ergonovine amounted to 93% of the total alkaloid in wheat
grain medium while lysergic acid derivatives and ergonovine comprised 66%
and 32% of the total alkaloids in rye grain medium, respectively [93].
The use of mathematical models in this system is a further advancement in
the field of research on the production of ergot alkaloids. The first model [94]
described a growth model for an ergotamine producing Claviceps purpurea in
submerged culture. In developing the model, the basic principles of the growth
and the morphological properties of the fungus were considered. The association between cell morphology, culture age, and ergot alkaloid production has
been well established, assuming that the growth occurs in a three-step manner.
The first involves the assimilation and the growth of the cells, the second cell
division, and the third transformation of the mature cells to a state where they
have no ability to divide but can produce the alkaloids and then gradually die.
As the limiting substrate for the first and second steps, inorganic phosphate was
presumed in the condition of the carbon source, sucrose being in excess.
Another mathematical model [95] for the batch cultivation of Claviceps purpurea 129, producing clavine alkaloids, was formulated. The effect of extracellular and intracellular phosphate on the growth of the cells and production of
clavine alkaloid under experimental conditions without carbon and nitrogen
limitation was the objective of their study. The method of nonlinear regression
was used to predict the optimal strategy of the phosphate addition in the batch
culture at different time intervals of addition. In another study, kinetic parameters of production of clavine alkaloids were evaluated in two Claviceps
purpurea strains [96]. Addition of glucose into the fermentation medium
altered the zero order kinetics of production to activation-inhibition kinetics.
The activation-inhibition kinetics of agroclavine and elymoclavine indicated
the possibility of developing an integrated fermentation and separation unit in
a closed loop, the cultivation of Claviceps purpurea being possible at the
physiological maximum of specific alkaloid production rates. A new mathematical model was developed for the production of lysergic acid by Claviceps
paspali [97]. The authors described an on-line modeling and control of a fedbatch fermentation process using a set of off-line identified models and their
respective optimal control curves. Their concept was tested through simulation
using experimental data from large scale fermentations and had given enProgress and Prospects of Ergot Alkaloid Research
15
no increase in the total alkaloid content for Claviceps purpurea, the content of
ergonovine and ergotamine was higher, which is important from the commercial point of view. Further work [92] with Claviceps purpurea 1029c involving impregnation of the inert solid support, sugar cane pith bagasse, with
16 different combinations of the liquid nutrient medium such as rye meal or
sucrose as the carbon source, ammonium sulphate, urea, and ammonium
oxalate as the nitrogen source(s), other nutrients, namely potassium dihydrogen phosphate, magnesium sulphate, calcium nitrate, citric acid, and the amino
acids valine, proline, tryptophan, and Tween 80 showed that there was a
significant change in the alkaloid spectra and the authors suggested the possibility of achieving tailor-made spectra of ergot alkaloids, economically. Use of
different solid substrates also resulted in major changes in the spectra of
alkaloids produced. Ergonovine amounted to 93% of the total alkaloid in wheat
grain medium while lysergic acid derivatives and ergonovine comprised 66%
and 32% of the total alkaloids in rye grain medium, respectively [93].
The use of mathematical models in this system is a further advancement in
the field of research on the production of ergot alkaloids. The first model [94]
described a growth model for an ergotamine producing Claviceps purpurea in
submerged culture. In developing the model, the basic principles of the growth
and the morphological properties of the fungus were considered. The association between cell morphology, culture age, and ergot alkaloid production has
been well established, assuming that the growth occurs in a three-step manner.
The first involves the assimilation and the growth of the cells, the second cell
division, and the third transformation of the mature cells to a state where they
have no ability to divide but can produce the alkaloids and then gradually die.
As the limiting substrate for the first and second steps, inorganic phosphate was
presumed in the condition of the carbon source, sucrose being in excess.
Another mathematical model [95] for the batch cultivation of Claviceps purpurea 129, producing clavine alkaloids, was formulated. The effect of extracellular and intracellular phosphate on the growth of the cells and production of
clavine alkaloid under experimental conditions without carbon and nitrogen
limitation was the objective of their study. The method of nonlinear regression
was used to predict the optimal strategy of the phosphate addition in the batch
culture at different time intervals of addition. In another study, kinetic parameters of production of clavine alkaloids were evaluated in two Claviceps
purpurea strains [96]. Addition of glucose into the fermentation medium
altered the zero order kinetics of production to activation-inhibition kinetics.
The activation-inhibition kinetics of agroclavine and elymoclavine indicated
the possibility of developing an integrated fermentation and separation unit in
a closed loop, the cultivation of Claviceps purpurea being possible at the
physiological maximum of specific alkaloid production rates. A new mathematical model was developed for the production of lysergic acid by Claviceps
paspali [97]. The authors described an on-line modeling and control of a fedbatch fermentation process using a set of off-line identified models and their
respective optimal control curves. Their concept was tested through simulation
using experimental data from large scale fermentations and had given enProgress and Prospects of Ergot Alkaloid Research
15