Zhu Dunming, Yang Yan, Majkowicz Stephanie, Pan Thoris Hsin-Yuan, Kantardjieff Katherine, Hua Ling
Department of Chemistry, Southern Methodist University, Dallas, Texas 75275, USA.
Org Lett. 2008 Feb 21;10(4):525-8. doi: 10.1021/ol702638j. Epub 2008 Jan 19.
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.
对来自鲑色掷孢酵母的一种羰基还原酶进行基于底物-酶对接引导的点突变，得到了突变酶，这些突变酶逆转了对映体选择性，并增强了对对位取代苯乙酮还原反应的对映体选择性。对映体选择性的这种显著变化表明，催化位点中的245位残基在决定这些酮还原反应的对映体选择性方面起着关键作用，这为我们理解参与底物结合的残基如何影响结合底物的取向从而控制还原立体选择性提供了有价值的见解。
