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Improvement of a Stereoselective Biocatalytic Synthesis by Substrate and Enzyme Engineering: 2‐Hydroxy‐(4′‐oxocyclohexyl)acetonitrile as the Model
Author(s) -
Avi Manuela,
Wiedner Romana M.,
Griengl Herfried,
Schwab Helmut
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800609
Subject(s) - biocatalysis , substrate (aquarium) , selectivity , chemistry , acetonitrile , combinatorial chemistry , ketone , stereoselectivity , enzyme , protein engineering , organic chemistry , catalysis , reaction mechanism , biology , ecology
Even if biocatalysis is finding increasing application, it still has to gain widespread use in synthetic chemistry. Reasons for this are limitations that enzymes have with regard to substrate range, reaction scope, and insufficient selectivity with unnatural compounds. These shortcomings can be challenged by enzyme and/or substrate engineering, which are employed to alter substrate specificity and enhance the enzyme selectivity toward unnatural substrates. Herein, these two approaches are coupled to improve the hydroxynitrile lyase catalyzed synthesis of 2‐hydroxy‐(4′‐oxocyclohexyl)acetonitrile ( 4 ). The ketone functionality is masked as an enol ether, and the oxynitrilase of Hevea brasiliensis is engineered towards this masked substrate to give the product with a high optical purity and to drastically lower the amount of enzyme needed.