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5
Multi-Enzyme Systems and Cascade Reactions Involving
Cytochrome P450 Monooxygenases

Vlada B. Urlacher and Sebastian Schulz

5.1
Introduction

5.1.1
Multistep Cascade Reactions
The use of enzymes in industrial processes is fairly old; for example, pancreas
extracts containing pancreatic proteases were used in leather bating and as detergent
additives already in the 1920s. The advent of immobilization technologies, turning
quite labile enzymes into rather stable biocatalysts, expanded this field considerably.
Thus, the preparation of chiral amino acids from racemic amides by the use of
immobilized amidases and the manufacture of 6-aminopenicillanic acid from
penicillin G using immobilized penicillin acylase were important milestones in the
field of biotransformations in the 1960s and 1970s [1–3].
Genetic engineering techniques, widely introduced in the 1980s, have initiated
a revolution in biotransformations. Enzymes from any source of life can now be
conveniently prepared by microbial host strains, and further improved for selectivity
and stability using protein engineering techniques. In contrast to fermentation
processes that imply the de novo synthesis of chemicals from a carbon and
energy source such as glucose, most biotransformations start from relatively
complex precursor organic molecules that are converted through only one or a
few biochemical reactions into the desired product. Biocatalytic applications can be
performed either with isolated enzymes or with whole-cell catalysts [4].
Recently, multistep enzyme-catalyzed reactions have attracted the attention of
chemists and biotechnologists, as they can be combined in a modular manner and
often lead to high-value compounds. All naturally occurring metabolic pathways
are basically cascade reactions. Based on natural principles, synthetic chemists
search for universal multistep processes applicable to a vast number of chemical
compounds. Multistep enzyme-catalyzed reactions involving nonphysiological
substrates and selective enzymes are of particular interest because they may lead
to tailor-made complex molecules with desired properties. Moreover, one of the
most important advantages of multistep enzyme-catalyzed reaction sequences

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.