5 - Max-Planck-Institut für Kohlenforschung

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Synthetic Organic Chemistry - M. T. Reetz
2.1.3 Research Area "Directed Evolution as a Means to Create
Selective Hybrid Catalysts" (M. T. Reetz)
Involved: A. Maichele, F. Hollmann, M. Maywald, J. Peyralans, A. Pletsch,
M. Rentzsch, A. Taglieber
Objective: The directed evolution of enantioselective enzymes constitutes a novel and
powerful approach to asymmetric catalysis, but by nature it is limited to enzyme-
catalyzed reactions. The vast number of synthetic opportunities arising from transition
metal-mediated processes such as Rh-catalyzed olefin hydrogenation and
hydroformylation, Ru-catalyzed olefin metathesis, Pd-catalyzed allylic substitution, etc.,
are not possible in enzyme catalysis. In 2001 we proposed a concept which has the
potential of going beyond this natural limitation.
The concept is based on the idea of implanting a given achiral ligand/metal-center in
thousands of mutant enzymes (proteins) previously created by the various methods of
random mutagenesis known in the field of directed evolution. The protein does not
perform as an enzyme, its sole purpose is to function as a host and therefore as a
"second-sphere ligand". By going through several cycles of mutagenesis, chemical
modification and screening, an evolutionary pressure is exerted on the system.
Theoretically, this means that the methods of molecular biology are used to tune a
synthetic transition metal catalyst for any desired property.
mutagenesis
DNA
gene library
mutagenesis
expression
-SH
protein
protein
library
catalyst
chemical
modification
ee-screening
-S
protein
hybrid
catalysts
M