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58 3 Monooxygenase-Catalyzed Redox Cascade Biotransformations

representative examples of the combination of homogeneous–homogeneous or of
heterogeneous–homogeneous catalysis involving monooxygenases.
A milestone in this research area has been the recent publication by the groups
of Turner, Hollmann, and Ward [39]. The concept of this work was based on
the design of artificial metalloenzymes in which an organometallic catalyst was
incorporated in a protein scaffold (Scheme 3.18).

Substrates Biocatalyst

Mutual inactivation Intermediate

Incorporation
Product
Metal-catalyst
Metal-catalyst Scaffold

Scheme 3.18 Conceptual view of chemo-enzymatic cascade reactions mediated by artificial
metalloproteins and a biocatalyst.

They presented reaction cascades resulting from combining an organometallic
transfer-hydrogenation catalyst [Cp*Ir(biotp-L)Cl] (artificial transfer hydrogenase,
ATHase) with a biocatalyst. Relying on the strength of the biotin–streptavidin
interaction, incorporation of the biotin-bearing complex [Cp*Ir(biot-p-L)Cl] within
streptavidin (Sav) yielded in an ATHase that was fully compatible with and
complementary to a variety of natural enzymes. Scheme 3.19 shows an example
of these cascade transformations in which the previously described ATHase was

(air)
O 2 HO
CO 2 NADH

ATHase S112A HbpA
HO

HO
HCOOH NAD +
H 2 O

Scheme 3.19 Metalloenzyme ATHase S112A combined in a chemo-enzymatic cofactor recy-
cling system for the oxygenation reaction catalyzed by the hydroxybiphenyl monooxygenase
from P. azaleica.