particles to the reactor wall. Vibrating the whole reactor could not elucidate this. This
indicates that further improvements of the mixing process in reactors for solid-to-solid
bioconversions are thus still necessary.
With respect to the kinetics of solid-to-solid bioconversions, hardly any literature is
available that goes beyond data on the biokinetics. However, for appropriate design,
optimisation, and control of a batch or continuous system for solid-to-solid
bioconversions, mechanistic models should also include the kinetics of dissolution and
crystallisation. Only recently, we have reported the first mechanistic model for the
conversion of a solid substrate salt to a solid product salt (type 4 conversion) in a batch
stirred bioreactor seeded with product crystals (Michielsen et al., 1999a). This model
accounts for the kinetics of salt dissolution, the biokinetics (both the kinetics of
conversion and of biocatalyst inactivation), and the salt crystal growth kinetics; salt
dissociation and complexation of ions in the liquid phase were assumed to be at
equilibrium. The model gave a good quantitative prediction of the conversion of solid Ca-
maleate to solid Ca-D-malate by permeabilised Pseudomonas pseudoalcaligenes in a
batch stirred bioreactor seeded with Ca-D-malate crystals (see Figure 8.3). As the
parameters in the model were determined as a function of relevant process conditions,
like temperature, the model could be used to predict the rate (and the conversion) as a
function of these process conditions. It should be noted that the model can only be
applied for well-mixed suspensions, as the effect of mixing was not incorporated.
From these kinetic studies we can conclude on the one hand that in batch systems with
very high concentrations of undissolved substrate, and thus with a very small liquid
phase, high rates per mass unit of enzyme are possible, if appropriate solids mixing can
be provided. Since this can be combined with a high conversion and easy scale-up (see
Table 8.1), these systems become attractive for commercial application. On the other
hand, our kinetic model for one type of solid-to-solid bioconversions offers possibilities
for good control of such conversions. Since the latter is an important prerequisite for
reliable and stable operation of continuous systems (see below), a further development of
these systems is quite opportune. Proposals for such developments are given below.
Multiphase bioreactor design 244