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Directed Evolution of Stereoselective Hybrid Catalysts

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Topics in Organometallic Chemistry

Part of the book series: Topics in Organometallic Chemistry

Abstract

Whereas the directed evolution of stereoselective enzymes provides a useful tool in asymmetric catalysis, generality cannot be claimed because enzymes as catalysts are restricted to a limited set of reaction types. Therefore, a new concept has been proposed, namely directed evolution of hybrid catalysts in which proteins serve as hosts for anchoring ligand/transition metal entities. Accordingly, appropriate genetic mutagenesis methods are applied to the gene of a given protein host, providing after expression a library of mutant proteins. These are purified and a ligand/transition metal anchored site-specifically. Following en masse ee-screening, the best hit is identified, and the corresponding mutant gene is used as a template for another round of mutagenesis, expression, purification, bioconjugation, and screening. This allows for a Darwinian optimization of transition metal catalysts.

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Abbreviations

BINOL:

Binaphthol

BSA:

Bovine serum albumin

CAST:

Combinatorial active-site saturation test

cod:

1,5-Cyclooctadiene ee Enantiomeric excess

epPCR:

Error-prone polymerase chain reaction

ESI-MS:

Electro-spray ionization mass spectrometry

ESI-TOF MS:

Electro-spray ionization time of flight mass spectrometry

HSA:

Human serum albumin

IPTG:

Isopropyl-β-d-thiogalactopyranoside

ISM:

Iterative saturation mutagenesis

L-BAPNA:

N-Benzoyl-l-arginine-p-nitroanilide

LB-medium:

Luria–Bertani medium

MALDI-TOF-MS:

Matrix assisted laser desorption ionization time of flight mass spectrometry

MS:

Mass spectrometry

PCR:

Polymerase chain reaction

SDS PAGE:

Sodium dodecylsulfate polyacrylamide gel electrophoresis

TB-medium:

Terrific broth

WT:

Wild-type

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  1. Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim/Ruhr, Germany

    Manfred T. Reetz

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Reetz, M. (2008). Directed Evolution of Stereoselective Hybrid Catalysts. In: Topics in Organometallic Chemistry. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3418_2008_12

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