Inverting the enantioselectivity of a carbonyl reductase via substrate-enzyme docking-guided point mutation.
Substrate-enzyme docking-guided point mutation of a carbonyl reductase from Sporobolomyces salmonicolor led to mutant enzymes, which reversed the enantiopreference and enhanced the enantioselectivity toward the reduction of para-substituted acetophenones. Such a dramatic change in the enantioselectivity indicates that the 245 residue in the catalytic site plays a critical role in determining the enantioselectivity of these ketone reductions, providing valuable insight into our understanding of how residues involved in substrate binding affect the orientation of bound substrate and thus control the reduction stereoselectivity.
Zhu
Dunming
D
Department of Chemistry, Southern Methodist University, Dallas, Texas 75275, USA. dzhu@smu.edu
Yang
Yan
Y
Majkowicz
Stephanie
S
Pan
Thoris Hsin-Yuan
TH
Kantardjieff
Katherine
K
Hua
Ling
L
D000098:Acetophenones / Q000737:chemistry*; D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000235:genetics; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D001487:Basidiomycota / Q000201:enzymology*; D001665:Binding Sites; D007659:Ketones / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017354:Point Mutation; D013237:Stereoisomerism; D013379:Substrate Specificity
D000098:Acetophenones; D007659:Ketones; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase