Fed-Batch Bioproduction of Spectinomycin
21
the residual glucose concentration approaches the optimum, the span (T6) of the
first level of saturation reduces. As the glucose feed concentration approaches
the optimum, the allocation of the carbon and oxygen resource is such that the
microorganism preferentially chooses the high yield path. Consequently, it
utilizes the low yield path to a lesser extent and hence the duration of the
intermediate saturation level reduces. We have not determined which branch of
glucose-6-phosphate leads to higher yields of spectinomycin. However, we have
observed that this span is 36 h and the longest for the glucose feed concentration
of 125 gl- 1. In the case of glucose feed concentrations of 100 gl- 1 and 175 gl- 1,
it is approximately 30 h. The smallest span of 12 h occurs when the glucose
feed concentration is 150 g l-1, which is the optimum. However, two different
saturation levels were not observed in the last case where the glucose feed
concentration was 400 g 1-1. Hence, for high glucose feed concentrations such as
400 g 1-1 a different mechanism of resource allocation and uptake exists. Unfortunately, there is insufficient information to make further comments on this
phenomenon.
4.3 Influence of Residual Glucose Concentration
The residual glucose concentration is a good indicator of spectinomycin productivity in a production schedule. In Fig. 6 a typical profile is presented. There are
two different levels of the possible residual glucose concentration. The higher
level of about 3.5 g 1-1 corresponds to a higher yield of spectinomycin, whereas,
the lower residual glucose concentration level of about 0.5 g 1-1 corresponds to
a lower yield. As the glucose feed concentration approaches the optimum value,
the residual glucose concentration remains at the higher level for a longer
duration. This indicates that near the optimum, the glucose feed is sufficient to
meet the needs of maintenance and spectinomycin biosynthesis without becoming inhibitory or exhausting [48]. However, at glucose feed concentrations both
higher and lower than the optimum, the residual glucose concentration remains
at the lower level for most of the production phase. Also, in these cases, the
residual glucose concentration increases towards the later part of the bioproduction. At the same time a finite glucose uptake rate exists. Possibly, a switch
between biosynthetic pathways occurs to counter the sub-optimal conditions
and enables the microorganism to survive.
The residual glucose concentrations for all cases are presented in Table 1.
A proper analysis would require the consideration of both the residual glucose
concentrations and the glucose uptake rates. Note that the glucose uptake rate
has an increasing trend from the glucose feed concentration of 100-400 g1-1.
For glucose feed concentrations of 100 g 1-1 and 125 g 1-x the residual glucose
concentrations are, 0.71 g1-1 and 0.53 g1-1, respectively. In these cases the
corresponding glucose uptake rates are 3.3 g h- 1 and 3.75 g h- 1. Thus, although
the glucose feed concentration and the glucose uptake rate increased, the
residual glucose concentration failed to increase. Therefore, even at a glucose
21
the residual glucose concentration approaches the optimum, the span (T6) of the
first level of saturation reduces. As the glucose feed concentration approaches
the optimum, the allocation of the carbon and oxygen resource is such that the
microorganism preferentially chooses the high yield path. Consequently, it
utilizes the low yield path to a lesser extent and hence the duration of the
intermediate saturation level reduces. We have not determined which branch of
glucose-6-phosphate leads to higher yields of spectinomycin. However, we have
observed that this span is 36 h and the longest for the glucose feed concentration
of 125 gl- 1. In the case of glucose feed concentrations of 100 gl- 1 and 175 gl- 1,
it is approximately 30 h. The smallest span of 12 h occurs when the glucose
feed concentration is 150 g l-1, which is the optimum. However, two different
saturation levels were not observed in the last case where the glucose feed
concentration was 400 g 1-1. Hence, for high glucose feed concentrations such as
400 g 1-1 a different mechanism of resource allocation and uptake exists. Unfortunately, there is insufficient information to make further comments on this
phenomenon.
4.3 Influence of Residual Glucose Concentration
The residual glucose concentration is a good indicator of spectinomycin productivity in a production schedule. In Fig. 6 a typical profile is presented. There are
two different levels of the possible residual glucose concentration. The higher
level of about 3.5 g 1-1 corresponds to a higher yield of spectinomycin, whereas,
the lower residual glucose concentration level of about 0.5 g 1-1 corresponds to
a lower yield. As the glucose feed concentration approaches the optimum value,
the residual glucose concentration remains at the higher level for a longer
duration. This indicates that near the optimum, the glucose feed is sufficient to
meet the needs of maintenance and spectinomycin biosynthesis without becoming inhibitory or exhausting [48]. However, at glucose feed concentrations both
higher and lower than the optimum, the residual glucose concentration remains
at the lower level for most of the production phase. Also, in these cases, the
residual glucose concentration increases towards the later part of the bioproduction. At the same time a finite glucose uptake rate exists. Possibly, a switch
between biosynthetic pathways occurs to counter the sub-optimal conditions
and enables the microorganism to survive.
The residual glucose concentrations for all cases are presented in Table 1.
A proper analysis would require the consideration of both the residual glucose
concentrations and the glucose uptake rates. Note that the glucose uptake rate
has an increasing trend from the glucose feed concentration of 100-400 g1-1.
For glucose feed concentrations of 100 g 1-1 and 125 g 1-x the residual glucose
concentrations are, 0.71 g1-1 and 0.53 g1-1, respectively. In these cases the
corresponding glucose uptake rates are 3.3 g h- 1 and 3.75 g h- 1. Thus, although
the glucose feed concentration and the glucose uptake rate increased, the
residual glucose concentration failed to increase. Therefore, even at a glucose