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244 10 Perspectives on Multienzyme Process Technology

as transport phenomena, number of phases involved, and the degree of mixing.
In this way, the characteristics can be included into the mass balances using the
corresponding mathematical expression that described the phenomena. Good
reactor design is a key issue to achieve multienzyme process improvements, and
then it is also important to consider and analyze different types of reactors and
configurations that can best handle the process limitations.
• Component characteristics: in addition to the physical and chemical properties of
the components, it is also necessary to provide specifications such as purities
of substrates, concentrations, amounts of cofactors, and enzyme format (e.g.,
the whole cell, isolated, immobilized). This information is part of the initial
conditions of the process and is then used for the simulation of the model.
Furthermore, they contribute to the decision making about operating mode and
type of reactor.
• Process control: in multienzyme processes, variables such as pH and temperature
are often controlled during the process in order to reduce the influence that
they produce on the dynamics of other variables and enzymes. For modeling,
the controlled variables need to be identified in order to limit the capabilities of
the model. In this case, they are included as assumptions of the model. Process
control can be divided into two basic control layers [43]. The first is known as
the regulatory layer, which controls variables such as pH and temperature. In this
case, a simple controller design can be implemented. The second is known as
the supervisory layer, which manages variables with more impact on the process
such as concentrations of the compounds. In this case, a more detailed controller
design is required. For multienzyme processes, this issue is highly relevant
especially to achieve process improvements.

10.7
Future

It is clear that for the future it will be necessary to integrate bioprocesses into
existing chemical plants. Today the cost of most chemical plants is already written-
off, so replacement is not an easy option. In stages it seems likely that (1) capacity
increases will be absorbed by bioprocesses and later (2) retrofit of existing processes
will be carried out. At first, a significant majority of steps will remain chemically
based and later bioprocesses will expand into the majority if not the entire process.
Finally, it is clear that bioprocesses which operate under mild conditions (neutral
pH, atmospheric pressure, and ambient temperature) will enable options for the
process plant to be made from cheaper materials of construction. In some areas
of bioprocessing disposable plant and polypropylene based tanks and pipes are
already being used. Clearly this will have important consequences for plant design
and investment of capital.
In the future, protein engineering [44, 45] combined with genetic engineering
and expression engineering will enable alteration of biocatalysts such that designer
catalysts will become possible, ultimately ensuring integrated operation in one pot,