Multiphase Bioreactor Design

TE is the eutectic temperature (adapted

from Gill and Vulfson, 1994).

In order to make an appropriate choice, if possible, between the four types of systems
for a specific bioconversion, the following rules of thumb can be given:

• When the biocatalyst shows a high activity and stability in the liquid phase consisting of
  either one (type 1) or both substrates (type 2) at the reaction temperature, systems of
  types 1 and 2 are to be preferred, as the number of components in the final product
  suspension is minimal. The latter facilitates downstream processing.


• When the biocatalyst limits the use of systems of types 1 and 2, a solvent should be
  selected in which the biocatalyst shows a high activity and stability, and systems of
  type 3 should be created. Preferably the solubility of the product in the solvent should
  be low, as in case of equilibrium reactions the conversion increases, and in case of
  irreversible reactions the amount of solid product increases with decreasing product
  solubility.


• When the substrate(s) and/or the product(s) inhibit the biocatalyst, systems of type 3 or
  of type 4 should be created. For systems of type 3, the solvent should be selected on
  the basis of the same criteria as described above. Only when (also) substrate inhibition
  occurs, the substrate solubility in the solvent should be low as well. In systems of type
  4, solubility and thus inhibition can be minimised by addition of an appropriate
  counter-ion to the aqueous solution. The extent to which the substrate and product
  concentrations (in the liquid phase) are lowered can be controlled by the amount of
  salt added.

Conversion And Scale

Table 8.1 gives for every type of solid-to-solid bioconversions the reported range of the
conversion and of the scale. For every type, examples exist in which conversions of 80–
100% were obtained (Table 8.1). So far, most of the solid-to-solid bioconversions have
been executed on the mmol-scale. Eichhorn et al. (1997) have done the first scale-up of
solid-to-solid bioconversions for the production of Z-His-Phe-NH2 and Z-Aspartame
from the usual mmol-scale to a mol-scale in a stirred-tank reactor. Table 8.1 shows that,

Table 8.1 Comparison of the conversion and scale

of the four types of solid-to-solid bioconversions

according to Figure 8.1

Type Application area Conversion
(%)

Scale (mol) Sources

1 peptide synthesis 36–83 1.10–3–3. 10–3 Gill and Vulfson (1993)

2 peptide synthesis 21–84 0.3.10−^4 –
6.8.10−^2

Gill and Vulfson (1993)

López-Fandino et al.

(1994a, b)

Multiphase bioreactor design 242