Fed-Batch
Bioproduction
of Spectinomycin
39
0.06
2
4
0.05
..--,
~ 0.04
I~176
i
0.03
,"
'
~
0.02
0.01
0 i
----~--, I , , ~ , , , ,1~ ,
, , ~ , ,-',-','"
0
2
4
6
8
10
Glucose Concentration (g 1 1)
Fig. 24. Metabolic zones in spectinomycin
bioproduction
preferred metabolism corresponds to zone (2) and zone (3). Finally for the
glucose feed concentration of 400 g l-1 inhibition and decay dominated the
bioproduction corresponding to zone (4).
It is evident that the optimum operating range is narrow. Hence, controlling
the bioproduction in this range requires the implementation of an advanced
controller. Furthermore, the choice of the control variable plays an important
role in the performance of the controller. The glucose concentration takes
several hours to respond completely to an input or disturbance. Hence this
variable is unsuitable for implementing a direct control with stringent requirements, especially since the process is sensitive to changes. In comparison, the
oxygen response requires only a few minutes. Since the energetics of spectinomycin biosynthesis are coupled with the carbon regulation, spectinomycin
productivity can be controlled by controlling the air flow rate (dissolved oxygen)
along a predetermined optimal profile. The best set of optimum operating
conditions for spectinomycin bioproduction will involve both an optimal glucose feeding profile and a corresponding regulation of the dissolved oxygen
along an optimal profile. The derivation of the geometric control algorithm,
which has been implemented to control the dissolved oxygen and pH for
optimizing glucose feed as shown here, is presented elsewhere 1-49].
9 Conclusions and Future Prospects
Spectinomycin is an aminoglycoside antibiotic. Its synthesis begins from glucose-6-phosphate and proceeds along two branches to give the final product.
Bioproduction
of Spectinomycin
39
0.06
2
4
0.05
..--,
~ 0.04
I~176
i
0.03
,"
'
~
0.02
0.01
0 i
----~--, I , , ~ , , , ,1~ ,
, , ~ , ,-',-','"
0
2
4
6
8
10
Glucose Concentration (g 1 1)
Fig. 24. Metabolic zones in spectinomycin
bioproduction
preferred metabolism corresponds to zone (2) and zone (3). Finally for the
glucose feed concentration of 400 g l-1 inhibition and decay dominated the
bioproduction corresponding to zone (4).
It is evident that the optimum operating range is narrow. Hence, controlling
the bioproduction in this range requires the implementation of an advanced
controller. Furthermore, the choice of the control variable plays an important
role in the performance of the controller. The glucose concentration takes
several hours to respond completely to an input or disturbance. Hence this
variable is unsuitable for implementing a direct control with stringent requirements, especially since the process is sensitive to changes. In comparison, the
oxygen response requires only a few minutes. Since the energetics of spectinomycin biosynthesis are coupled with the carbon regulation, spectinomycin
productivity can be controlled by controlling the air flow rate (dissolved oxygen)
along a predetermined optimal profile. The best set of optimum operating
conditions for spectinomycin bioproduction will involve both an optimal glucose feeding profile and a corresponding regulation of the dissolved oxygen
along an optimal profile. The derivation of the geometric control algorithm,
which has been implemented to control the dissolved oxygen and pH for
optimizing glucose feed as shown here, is presented elsewhere 1-49].
9 Conclusions and Future Prospects
Spectinomycin is an aminoglycoside antibiotic. Its synthesis begins from glucose-6-phosphate and proceeds along two branches to give the final product.