Corynebacterium glutamicum - JUWEL - Forschungszentrum Jülich

3.4. Application: L-Valine Production Process Development
over f feeds include the feeds of glucose and of L-isoleucine with their known constant
carbon concentrations Ccf. The amount of carbon which is removed from the system
by sampling, is included as the sum over all m measurements until time t with sample
volume Vm and carbon concentrations Ccm. This concentration is estimated from the
concentrations of all measured compounds. The total amount of produced CO2 is included
as an integral over time and has also been addressed partly in paragraph 3.4.2
on page 54. Note that all concentrations in equation 3.14 are carbon concentrations,
so in [C − mole.L −1 ], which can readily be calculated from measured concentrations
and elemental composition of the compounds. This stoichiometry is simply known for
all regarded compounds except for the biomass. For the biomass, the measured concentrations
as OD600 are converted to biomass dry weight by multiplication with 0.25,
according to the measurements of both characteristics as mentioned in appendix B on
page 139. The amount of carbon per gram dry biomass is assumed to be 0.5 g/g, taken
from the values measured for a similar strain of C. glutamicum by Kelle (1996).
When all relevant products would be accounted for, equation 3.14 should hold. When
important products are unknown, the fraction C − bal of the carbon balance which is
accounted for, is calculated by rewriting the equation:
� t
t=0
C − bal =
((Fg,out(t)[CO2]out(t)) − (Fg,in(t)[CO2]in(t))dt)+ �
p Ccp(t)Vr(t)
− �
�
s Ccs(t)Vr(t)+ i Cci(0)V (0) + � � t
f t=0 Ff (t)Ccfdt − �
m VmCcm
.
(3.15)
Besides the degree to which the total carbon balance is closed, also the fractions of the
carbon fluxes into the different products is of interest. These values can be calculated
analogue to equation 3.15, after omitting all other products from the enumerator.
Total Volumetric Productivity
The total volumetric productivity is used as the optimization criterion for process optimization
of the L-valine production process. This characteristic value is also sometimes
called the space-time-yield and it consists of the amount of product which can be produced
per unit volume of suspension and time, calculated over the total process time.
Here, it is calculated as the increase in concentration of L-valine from the start of the
experiment up to each time-point, divided by the time:
TVP(t) = (Cval(t) − Cval(0))
. (3.16)
t
In the optimization of the process, the time-dependent total volumetric productivity
TVP(t), is calculated for each measurement time point and the highest value is taken.
The optimized process is stopped at the corresponding time-point.
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