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4
Biocatalytic Redox Cascades Involving -Transaminases

Robert C. Simon, Nina Richter, and Wolfgang Kroutil

4.1
Introduction

Chiral amines and their derivatives represent one of the most fundamental and
abundant functional groups in nature. As such, they can be found in amino acids,
hence in proteins, and various other bioactive molecules such as alkaloids, hor-
mones, neurotransmitters, and many more. From a chemical point of view, they are
valuable intermediates and precursors as well as important targets for pharmaceuti-
cals, polymers, dyes, fine chemicals, and agrochemicals. Consequently, numerous
sophisticated methods have been developed that provide amines in racemic as well
as in enantiomerically pure form [1], for which improved procedures are desired. In
particular, progressive legislative regulations regarding process, safety, and quality
improvements, together with cost, time, and energy reductions, require the pro-
vision of any desired target molecule in the most economical and ecological way.
One important strategy is the replacement of processes utilizing stoichiometric
amounts of reagents by catalytic procedures [2]. Biocatalysis meets several of these
requirements and has gained enhanced attention because of its excellent regio- and
stereoselectivities under mild and benign reaction conditions [3]. Furthermore, the
enormous progress made in protein engineering has allowed tailoring proteins for
designated process conditions representing therefore a promising alternative to
pure chemical methods, especially for industrial purposes [4]. Classical biocatalyt-
ical strategies to provide optically pure amines include the use of hydrolases [5],
monoamine oxidases (MAOs) [6], amino acid dehydrogenases (AADHs) [7], and,
more recently, amine dehydrogenase (AmDH) [8] and ω-transaminases (ω-TAs)
[9]. The latter are perfectly suited for asymmetric syntheses since these enzymes
feature a broad substrate spectra affording the product amines from the corre-
sponding ketones generally with high stereocontrol. Even though they have already
been proven to be remarkable in single-step operations providing diverse chiral
amines [10], the overall efficiency could be improved if several reaction steps
were combined in a sequential or concomitant cascade reaction. The replacement
of multistep reactions through a single enzymatic transformation or combining
several enzymes within a single flask has opened unexpected capabilities and

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.