capillary membrane reactor 1999
(acylase) resolution of N-acetyl-D, L-derivatives. In a 1400 hour pilot plant experiment
an approximate productivity of 10 kg of L-methionine per day was achieved (69%
conversion), and in a combined 2300 hour experiment, 366 kg of L-methionine and 179
kg of L-phenylalanine were prepared consecutively (82–86% conversion). A production
plant has even been conceived and constructed for the acylase-catalysed resolution of
acetyl-D, L-amino acids with a capacity of 15–20 tons per month of L-amino acids
(Leuchtenberger et al., 1984). The fumarase catalyzed stereoselective production of L-
malic acid from fumaric acid was also conducted in a similar 10 litre enzyme membrane
reactor. In a 800 hour experiment, 300 kg of L-malic acid were produced with an
approximately constant conversion of 70%, maintained by addition of fresh enzyme
(Leuchtenberger et al., 1984).
Two examples listed in Table 6.9 describe the use of enzymatic membrane reactors in
environmental applications (Bodzek et al., 1994; Edwards et al., 1999). Both cases report
on the degradation of phenols from model and industrial wastewaters. In one case
bacterial hydroxilases and oxygenases isolated from microorganisms in activated sludge
were used in an ultrafiltration cell (Bodzek et al., 1994), while in the other a commercial
polyphenol oxidase was used with a capillary membrane module (Edwards et al., 1999).
The complexity that is possible to achieve in a membrane reactor is exemplified by a
recent publication, which describes the synthesis of a protein, chloramphenicol
acetyltransferase, by the direct in vitro expression from a PCR (polymerase chain
reaction) template (Nakano et al., 1999). The authors have used a diffusion type reactor,
where the enzyme T7 RNA polymerase and an Escherichia coli S30 cell extract were
placed in the shell side of an hollow fibre module. The PCR template was also trapped in
the shell side. A substrate rich solution, containing the nucleotides ATP, CTP, GTP, UTP
and 20 aminoacids, was recirculated through the fibres lumen. In this system, substrates
diffuse to the shell side where the translation of the DNA template into messenger RNA
is catalysed by T7 RNA polymerase. The transcription of mRNA into protein then occurs
at the E. coli ribosomes from cell extract. The membrane reactor used thus mimics a
living cell in its task of synthesising proteins.
Additional applications of membrane reactors include the hydrolysis of urea (Gacesa
et al., 1983; Yonese et al., 1990), the synthesis of (R)-mandelonitrile (Kragl et al.,
1990a), the synthesis of N-acetylneuraminic acid (Kragl et al., 1990b, 1990e), the
production of peroxycarboxylic acids and epoxides by lipase (Cuperus et al, 1994), the
oxidation of indole to oxindole by chloroperoxidase (Seelbach et al., 1997) and the
oxidation of cephalosporin C by D-aminoacid oxidase immobilised on Duolite A365
(Alfani et al., 1998).
CONCLUSIONS AND FUTURE PROSPECTS
In recent years, membrane reactors have established themselves as an alternative
configuration for enzymatic reactors. The unique advantages offered by these reactors
together with the wide variety of membrane shapes, modules and materials commercially
available, have made them an alternative to more conventional reactors such as fixed or
Multiphase bioreactor design 178