Multiphase Bioreactor Design

and operation above critical pressures or below critical temperatures. The need to ensure
the safe operation of two-phase biotransformations will lead to increased capital and
operating costs compared to traditional fermentation processes.

INDUSTRIAL EXAMPLES

Although a detailed understanding of the mass transfer and kinetic phenomena
underlying the scale-up of two-liquid phase biocatalytic processes is only now beginning
to emerge, a number of processes have been scaled-up on an empirical basis to either
large-pilot or full process scale. Examples are summarised in Table 5.4. While a number
of these processes have been operated commercially, there is little information in the
literature regarding the economics of two-liquid phase processes. Such information is
vital if biocatalytic processes are to be chosen over competing chemical alternatives.
Mathys and coworkers (1999) recently published a detailed economic analysis for the
production of alkanols from n-alkanes at a 10,000 tonne per year scale using a whole-cell
biocatalyst. The downstream process sequence employed three phase separation stages
and a two-stage distillation process for product isolation and solvent recycle. In contrast
to many biological production processes the largest costs were associated with the
upstream, rather than the downstream, processing due to the medium costs. For a fed-
batch process the overall production cost for 1-octanol was estimated to be approximately
7 US$ kg−^1.

Table 5.4 Industrial examples of two-phase

biocatalytic processes

Reaction Biocatalyst Solvent Company References

l-octene
epoxidation

Nocardia corallina n-hexadecane Nippon

Mining

Furuhashi et al.

(1986)

Phenol
polymerisation

Horseradish

peroxidase

Ethyl acetate Mead Pokora and Cyrus

(1987)

Ester hydrolysis Subtilisin Bayer Schutt et al. (1985)
(immobilised) Lipase

Various

(reactant)

Sumitomo Umemura and

Hirohara (1989)

Steroid
dehydrogenation

Arthrobacter simplex Toluene Upjohn

Desulfurization Rhodococcus Oil (substrate) Energy Biosy
stems

Monticello (1993)

FUTURE PERSPECTIVES

Applications of Two-Phase Biocatalysis

Advances in the selection and design of two-liquid phase biocatalytic reactors 139