Fed-Batch Bioproduction of Spectinomycin
45
Activation-Reaction-Inhibition model
tinomycin are,
for the fed-batch production of specdC
( Ke S )
C dV
dPa
(__Kel
S )C_KdPl_P-21d~ V
d---~- = al/tp,exp
S
Kil
V dt
dP2
( Ke2
S )C__KaP2 P2 dV
d--~ = ~2 ~P2 exp -- S
Ki2
- -
-V d--T
dt - Yc~s o~ I~m exp 9 S Ki
YPxs cq #e~ exp
S
Ki~
1
( Ke2 S )
Sv SdV
- Ye2--~s ~2 ,ups exp
S
Ki2 C + -~ -- V d~
dV
-- = F
(A.7)
dt
Here a, ~x, and a2 are the activation components. The maximum specific growth
rate is Pro, and/~p, and/~,, the maximum specific product formation rates for
P1 and P2. Also Ke and Ki are the exponential model and the inhibition
constants for cell growth; whereas Kel, K,I and Ke2, Ki2 are exponential model
and inhibition constants for P~ and P2, respectively.
The activation terms are constant for the process and act as a trigger to
describe the change from lag phase to growth phase. They have the form
exp(a(S - b)/(1 + exp(a(S - b)). The two parameters a and b need to be evaluated only once, so that they match with the start of spectinomycin synthesis. In
subsequent estimation of the model parameters, a is simply treated as a constant
premultiplier. In this sense, it does not belong to the set of model parameters
evaluated by nonlinear regression. The estimation model parameters are presented in Table 2.
11 References
1. Martin JF, Demain AL (1980) Microbiol Rev 44:230
2. Lilley G, Rowley BI, Bull AT (1974) J Appl Chem Biotechnol 24:677
3. Gray PP, Bhuwapathanapun S (1980) Biotechnol Bioeng 22:1785
4. Hirsch CF (1981) In: Schlessinger D (ed) Regulation of secondary metabolism in microorganisms, Am Soc Microbiol, Washington DC
5. Aharonowitz Y (1980) Ann Rev Microbiol 34:209
6. Aharonowitz Y, Demain AL (1979) Can J Microbiol 25:61
7. Demain AL, Kennel YM, Aharanowitz Y (1979) Symp Soc Gen Microbiol 29:163
8. Basak K, Majumdar SK (1973) Antimicrob Agents, Chemother 4:6
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