40
J. Gomes and A.S. Menawat
The overall yield of spectinomycin depends on two key intermediates, 1,3-myoinosadiamine or actinamine. The dual maxima of spectinomycin with changing
glucose feed concentrations and the two level saturations in the spectinomycin
production profiles support this observation. Results suggest that the residual
glucose concentration determines the flux of the carbon source through the two
branches. Since one of these branches is energetically more favorable, there is
a distinct residual glucose concentration for which the spectinomycin yield is
maximum.
To describe the sharp changes from growth to production phase and the
rapid switch from one level of saturation to another, we proposed an ActivationReaction-Inhibition structure model. The classical Monod structure could not
account for the special characteristics of spectinomycin bioproduction. The
model comprised exponential kinetic structures in contrast to the hyperbolic
structures of the Monod type kinetics. It was demonstrated that the model
exhibited higher geometric and parameter sensitivity in comparison to the
Monod type model.
Using this Activation-Reaction-Inhibition model it is possible to correlate the
air flow rate to the antibiotic concentration. The EDR was developed for air
flow and spectinomycin measurements. For this prediction the cell mass concentration values were not known because they could not be measured. Hence, the
required cell mass concentration values for the prediction were evaluated with the
EDR. Air flow rate profiles reconstructed from the identified model compare well
with the raw data. Similarly, the spectinomycin concentrations were predicted
from the air flow rate. This result is significant because if the air flow rate profile
which gives highest spectinomycin yield is known, the process may be controlled
along this trajectory every time to consistently achieve maximum productivity.
However, there are several aspects of spectinomycin bioproduction which
need further investigation. The most important among them is to determine
which branch of the spectinomycin biosynthetic pathway is the energetically
favorable one. It would be critical also to determine the residual glucose
concentration necessary to keep this biosynthetic pathway active during the
entire production phase and study its variation at different scales of operation.
An idea of the actual fluxes in the pathway, bottle necks and correlation with the
EMP pathway will positively contribute to further enhancing the spectinomycin
yield.
Since methionine and cobalamine affect the amination reactions, their influence on the overall spectinomycin productivity may also be investigated. Other
important aspects relate to the effect of changing the glucose feeding rate during
the production phase and simultaneously implementing the corresponding
optimal air flow rate. Indeed a substantial amount of work remains with regard
to the contribution of external parameters on the yield of spectinomycin bioproduction.
Acknowledgements. This work was conducted at the Department of Chemical
Engineering. Tulane University, New Orleans, USA, and financially supported
J. Gomes and A.S. Menawat
The overall yield of spectinomycin depends on two key intermediates, 1,3-myoinosadiamine or actinamine. The dual maxima of spectinomycin with changing
glucose feed concentrations and the two level saturations in the spectinomycin
production profiles support this observation. Results suggest that the residual
glucose concentration determines the flux of the carbon source through the two
branches. Since one of these branches is energetically more favorable, there is
a distinct residual glucose concentration for which the spectinomycin yield is
maximum.
To describe the sharp changes from growth to production phase and the
rapid switch from one level of saturation to another, we proposed an ActivationReaction-Inhibition structure model. The classical Monod structure could not
account for the special characteristics of spectinomycin bioproduction. The
model comprised exponential kinetic structures in contrast to the hyperbolic
structures of the Monod type kinetics. It was demonstrated that the model
exhibited higher geometric and parameter sensitivity in comparison to the
Monod type model.
Using this Activation-Reaction-Inhibition model it is possible to correlate the
air flow rate to the antibiotic concentration. The EDR was developed for air
flow and spectinomycin measurements. For this prediction the cell mass concentration values were not known because they could not be measured. Hence, the
required cell mass concentration values for the prediction were evaluated with the
EDR. Air flow rate profiles reconstructed from the identified model compare well
with the raw data. Similarly, the spectinomycin concentrations were predicted
from the air flow rate. This result is significant because if the air flow rate profile
which gives highest spectinomycin yield is known, the process may be controlled
along this trajectory every time to consistently achieve maximum productivity.
However, there are several aspects of spectinomycin bioproduction which
need further investigation. The most important among them is to determine
which branch of the spectinomycin biosynthetic pathway is the energetically
favorable one. It would be critical also to determine the residual glucose
concentration necessary to keep this biosynthetic pathway active during the
entire production phase and study its variation at different scales of operation.
An idea of the actual fluxes in the pathway, bottle necks and correlation with the
EMP pathway will positively contribute to further enhancing the spectinomycin
yield.
Since methionine and cobalamine affect the amination reactions, their influence on the overall spectinomycin productivity may also be investigated. Other
important aspects relate to the effect of changing the glucose feeding rate during
the production phase and simultaneously implementing the corresponding
optimal air flow rate. Indeed a substantial amount of work remains with regard
to the contribution of external parameters on the yield of spectinomycin bioproduction.
Acknowledgements. This work was conducted at the Department of Chemical
Engineering. Tulane University, New Orleans, USA, and financially supported