Biomedical Engineering Reference
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Fig. 6 Simulation of biomass and product dynamic profiles on the basis of three elementary
modes (EM 63, EM 68, and EM 69) identified by functional enviromics: a biomass and product
concentration over time, and b elementary mode weighting factors over time
!
X
DP
dt
¼
X
i
dP
a
P
e
i
;
P
k
i
ð
20
Þ
A comparison between the model simulation and experimental measurements is
shown in Fig.
6
.
From the initial 4,119 elementary modes, 2,520, 960, 600, and 39 are for
biomass growth, scFv synthesis, simultaneous biomass growth and scFv synthesis,
and catabolism, respectively. It is interesting to note that the functional enviromics
algorithm identified EM 63 for product synthesis, which belongs to the second
group of 960 elementary modes. This suggested that the product is cell growth
dissociated, which is in agreement with our previous study [
60
]. Analysis of the
weighting factor dynamics (Fig.
6
b) clearly shows that the product synthesis
elementary mode peaks when the weighting factors for cell growth are almost
zero. The analysis of three additional fermentations further confirmed that product
synthesis is cell growth dissociated and that the final product titer increases with
the biomass concentration time integral. The maximum product titer and pro-
ductivity could be achieved by maximizing the glycerol feeding rate by applying
an accurate DO-stat glycerol feeding controller at very low DO set-points in the
range of 3-5 % [
60
].
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