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Enantioselective Reduction of Diaryl Ketones Catalyzed by a Carbonyl Reductase from Sporobolomyces salmonicolor and its Mutant Enzymes
Author(s) -
Li Hongmei,
Zhu Dunming,
Hua Ling,
Biehl Edward R.
Publication year - 2009
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200900045
Subject(s) - chemistry , enantioselective synthesis , borane , substituent , hydrosilylation , catalysis , enzyme , enantiomeric excess , yeast , aryl , stereochemistry , combinatorial chemistry , organic chemistry , biochemistry , alkyl
The carbonyl reductase from red yeast Sporobolomyces salmonicolor AKU4429 ( SSCR ) and its mutant enzymes effectively catalyzed the enantioselective reduction of diaryl ketones to give the corresponding chiral alcohols. Both conversion and enantioselectivity were dependent on the co‐solvent in the reaction medium. Diaryl ketones with a para ‐substituent on one of the phenyl groups were reduced with high enantioselectivity (up to 99% ee ), which is difficult to achieve using chemical methods such as chiral borane reduction, asymmetric hydrogenation or hydrosilylation. Mutation of SSCR at Q245 resulted in a higher amount of ( S )‐enantiomer in the products, and in the case of mutant Q245P with para ‐substituted diaryl ketones as substrate, this effect was so remarkable that the reduction enantiopreference was switched from ( R ) to ( S ). The present study provides valuable information about the catalytic properties of the carbonyl reductase SSCR toward the reduction of diaryl ketones, serving as basis for further engineering of this enzyme to develop efficient biocatalysts for highly enantiospecific reduction of diaryl ketones without high electronic dissymmetry or an ortho ‐substituent on one of the aryl groups.