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Artificial Metalloenzymes for Enantioselective Catalysis Based on the Biotin–Avidin Technology

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Part of the book series: Topics in Organometallic Chemistry

Abstract

Artificial metalloenzymes can be created by incorporating an active metal catalyst precursor in a macromolecular host. When considering such artificial metalloenzymes, the first point to address is how to localize the active metal moiety within the protein scaffold. Although a covalent anchoring strategy may seem most attractive at first, supramolecular anchoring strategy has proven most successful thus far.

In this context and inspired by Whitesides’ seminal paper, we have exploited the biotin–avidin technology to anchor a biotinylated active metal catalyst precursor within either avidin or streptavidin. A combined chemical and genetic strategy allows a rapid (chemogenetic) optimization of both the activity and the selectivity of the resulting artificial metalloenzymes. The chiral environment, provided by second coordination sphere interactions between the metal and the host protein, can be varied by introduction of a spacer between the biotin anchor and the metal moiety or by variation of the ligand scaffold. Alternatively, mutagenesis of the host protein allows a fine tuning of the activity and the selectivity.

With this protocol, we have been able to produce artificial metalloenzymes based on the biotin–avidin technology for the enantioselective hydrogenation of N-protected dehydroaminoacids, the transfer hydrogenation of prochiral ketones as well as the allylic alkylation of symmetric substrates. In all cases selectivities >90% were achieved. Most recently, guided by an X-ray structure of an artificial metalloenzyme, we have extended the chemogenetic optimization to a designed evolution scheme. Designed evolution combines rational design with combinatorial screening. In this chapter, we emphasize the similarities and the differences between artificial metalloenzymes and their homogeneous or enzymatic counterparts.

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Abbreviations

ee:

Enantiomeric excess

WT:

Wild-type

Sav:

Streptavidin

Avi:

Avidin

(strept)avidin:

Either avidin or streptavidin

K M :

Michaelis–Menten constant

k cat :

Number of substrate molecules handled by one active site per second

v max :

Maximum velocity of the enzyme under the conditions of the experiment

DMSO:

Dimethyl sulfoxide

EtOAc:

Ethyl acetate

NBD:

Norbornadiene

COD:

Cyclooctadiene

MES:

2-(N-morpholino)ethanesulfonic acid

MOPS:

3-(N-morpholino)propanesulfonic acid

PYRPHOS:

(3R,4R)-3,4-bis(diphenylphosphino)pyrrolidine

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Authors and Affiliations

  1. Institute of Chemistry, University of Neuchâtel, Avenue de Bellevaux 51, CP 158, 2009 Neuchâtel, Switzerland

    Johannes Steinreiber & Thomas R Ward

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  1. Johannes Steinreiber
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  2. Thomas R Ward
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Correspondence to Thomas R Ward .

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© 2008 Springer-Verlag London

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Steinreiber, J., Ward, T. (2008). Artificial Metalloenzymes for Enantioselective Catalysis Based on the Biotin–Avidin Technology. In: Topics in Organometallic Chemistry. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3418_2008_3

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  • DOI: https://doi.org/10.1007/3418_2008_3

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