Stereoselective ketone reduction by a carbonyl reductase from Sporobolomyces salmonicolor. Substrate specificity, enantioselectivity and enzyme-substrate docking studies.
In our effort to search for effective carbonyl reductases, the activity and enantioselectivity of a carbonyl reductase from Sporobolomyces salmonicolor have been evaluated toward the reduction of a variety of ketones. This carbonyl reductase (SSCR) reduces a broad spectrum of ketones including aliphatic and aromatic ketones, as well as alpha- and beta-ketoesters. Among these substrates, SSCR shows highest activity for the reduction of alpha-ketoesters. Aromatic alpha-ketoesters are reduced to (S)-alpha-hydroxy esters, while (R)-enantiomers are obtained from the reduction of aliphatic counterparts. This interesting observation is consistent with enzyme-substrate docking studies, which show that hydride transfer occurs at the different faces of carbonyl group for aromatic and aliphatic alpha-ketoesters. It is worthy to note that sterically bulky ketone substrates, such as 2'-methoxyacetophenone, 1-adamantyl methyl ketone, ethyl 4,4-dimethyl-3-oxopentanoate and ethyl 3,3-dimethyl-2-oxobutanoate, are reduced to the corresponding alcohols with excellent optical purity. Thus, SSCR possesses an unusually broad substrate specificity and is especially useful for the reduction of ketones with sterically bulky substituents.
Zhu
Dunming
D
Department of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, USA.
Yang
Yan
Y
Buynak
John D
JD
Hua
Ling
L
D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D001487:Basidiomycota / Q000201:enzymology*; D001665:Binding Sites; D015870:Gene Expression; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013379:Substrate Specificity
D007659:Ketones; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase