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11
Nitrile Converting Enzymes Involved in Natural and Synthetic
Cascade Reactions

Ludmila Mart´ ınkov´ a, Andreas Stolz, Fred van Rantwijk, Nicola D’Antona, Dean Brady,
and Linda G. Otten

11.1
Introduction

Nitrile containing compounds are widely used in synthetic chemical industry and
are abundant in nature. Because they can be toxic, mutagenic, and carcinogenic as
they belong to the cyano group, nature has a plethora of enzymes to metabolize these
compounds very efficiently. The pathways involved in the metabolism of nitriles
in nature consist of an intricate pattern of fine-tuned enzymes (Figure 11.1),
which have been extensively studied over the last decades [1–6]. From a synthetic
perspective, nitriles are simple to synthesize through several organic chemical
pathways from cheap substrates. Therefore, they are important intermediates
in the chemical industry for production of amines, amides, amidines, carboxylic
acids, esters, aldehydes, ketones, and heterocyclic compounds. The use of biological
systems for the production of these commodity or specialty chemicals is a logical
alternative to traditional chemical methods, because of the high yields that can often
be obtained, the mild reaction conditions required, and the specialized activities
possessed by some enzymes [7].
The enzymatic part in organic synthesis is usually performed as a single step,
but because nature has attuned whole pathways to metabolize nitriles, the use of
multienzymatic cascade reactions is more often employed nowadays [8]. In these
organic synthesis processes, both natural cascades and man-made pathways are
used. This chapter describes the mechanisms and operation of both natural and
artificial cascades developed in the past decade. In addition to describing different
enzyme systems, each section shows synthetic applications in academic and
industrial settings using these cascades. Most described cascades show different
enzymatic actions on the same group of a molecule, but the last two sections show
how enzymatic cascades can also be performed on different regions of the same
molecule in order to get to more efficient synthetic pathways.

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.