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10
Perspectives on Multienzyme Process Technology

Paloma A. Santacoloma and John M. Woodley

10.1
Introduction

Today, the use of enzymes (either isolated, immobilized, or inside nongrowing cells)
finds application in many industries. The exquisite selectivity, combined with mild
operating conditions makes them particularly well suited for complex chemical syn-
theses involving highly functionalized molecules. However, regardless of the indus-
try sector, in all cases where biocatalysis has been implemented, it has delivered a
cost-effective process (often with the added bonus of sustainability). Enzymatic solu-
tions for the organic chemist, implemented to a greater or lesser extent in industry,
already include the use of lipases, C–N lyases and transaminases, C–C lyases, oxi-
doreductases, oxidases, and also isomerases [1]. To date, the major criticism leveled
at biocatalysis has been the lack of availability of enzymes at a low enough price
for effective implementation. However, today this too is addressed by a growing
band of companies (e.g., Codexis (USA), Enzymicals (DE), c-LEcta (DE), CLEA
technologies (NL)) specializing in enzyme manufacture for the organic chemist.
Nevertheless, one feature of the vast majority of these enzyme-based processes
in the chemical sector (in particular for the synthesis of pharmaceuticals) is that
thus far they have involved a single biocatalytic reaction step surrounded by
neighboring chemical reaction steps [2, 3]. Such an approach leads to synthetic
sequences that contain significant changes of conditions, such as pH, temperature,
pressure, and solvent, in order to accommodate the biocatalytic step in the midst
of more conventional chemistry. Hence, it has been argued for some time now,
that the more (sequential) the steps that can be made biocatalytic, the better. In
nature, complete pathways characterize the chemistry of the cells and using this
as a template seems eminently desirable. In organocatalysis, such an approach
is also being explored to create multicomponent, domino, and tandem reactions
[4]. Combining biocatalysis in this way is even more powerful because for the
first time now we can envisage biocatalysis, synthetic biology, and systems biology
with a similar, even if not yet identical, target. It is self-evident that not all steps
can be replaced by biocatalysis, nor is that even desirable, but it is clear now that
many new processes can be made possible by creating combinations of enzyme

Cascade Biocatalysis: Integrating Stereoselective and Environmentally Friendly Reactions, First Edition.
Edited by Sergio Riva and Wolf-Dieter Fessner.
c 2014 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2014 by Wiley-VCH Verlag GmbH & Co. KGaA.