Protein Engineering of Stereoselective Baeyer-Villiger Monooxygenases

Baeyer–Villiger monooxygenases (BVMOs) have been used for decades as catalysts in stereoselective Baeyer–Villiger reactions, including oxidative kinetic resolution of racemic ketones and desymmetrization of prochiral substrates with high enantioselectivity. These complement catalytic BV processes ba...

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Bibliographic Details
Published in:Chemistry : a European journal 2012-08, Vol.18 (33), p.10160-10172
Main Authors: Zhang, Zhi-Gang, Parra, Loreto P., Reetz, Manfred T.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Baeyer-Villiger monooxygenses
Biocatalysis
Catalysis
Catalysts
Chemistry
chirality
Complement
directed evolution
enzyme catalysis
Enzyme Stability
Evolution
Kinetics
Mixed Function Oxygenases - chemistry
Mixed Function Oxygenases - metabolism
Models, Molecular
Oxidation-Reduction
protein engineering
Protein Engineering - methods
Protein folding
Proteins
Stereoisomerism
Stereoselectivity
Substrate Specificity
Substrates
Temperature
Thermal stability
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Summary:Baeyer–Villiger monooxygenases (BVMOs) have been used for decades as catalysts in stereoselective Baeyer–Villiger reactions, including oxidative kinetic resolution of racemic ketones and desymmetrization of prochiral substrates with high enantioselectivity. These complement catalytic BV processes based on chiral synthetic catalysts. However, as in any enzyme‐catalyzed process, limitations exist due to the often observed narrow substrate scope and/or insufficient stereoselectivity. Recent protein engineering of BVMOs in the form of directed evolution and rational design have eliminated these traditional limitations, which is the subject of this Minireview. The main focus is on phenylacetone monooxygenase (PAMO); an unusually thermostable and robust BVMO, which has a very narrow substrate scope. Protein engineering of PAMO has provided a number of mutants that display relatively wide substrate scope, high stereoselectivity, and maintained thermostability. Evolution in a test‐tube: Directed evolution is a protein engineering method for manipulating the stereoselectivity and thermostability of enzymes as catalysts in organic chemistry (see figure). This Minireview summarizes the recent progress in the application of this method in the quest to create stereoselective mutants of Baeyer–Villiger monooxygenases.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201202163