Bailey Constance B, Pasman Marjolein E, Keatinge-Clay Adrian T
Department of Chemistry, University of Texas at Austin, 105 E. 24th St. Stop A5300, Austin, TX 78712, USA.
Chem Commun (Camb). 2016 Jan 14;52(4):792-5. doi: 10.1039/c5cc07315d.
Modular polyketide synthase ketoreductases can set two chiral centers through a single reduction. To probe the basis of stereocontrol, a structure-activity relationship study was performed with three α-methyl, β-ketothioester substrates and four ketoreductases. Since interactions with the β-ketoacyl moiety were found to be most critical, residues implicated in contacting this moiety were mutated. Two mutations were sufficient to completely reverse the stereoselectivity of the model ketoreductase EryKR1, converting it from an enzyme that generates (2S,3R)-products into one that yields (2S,3S)-products.
模块化聚酮合酶酮还原酶可以通过单次还原设定两个手性中心。为了探究立体控制的基础，我们使用三种α-甲基-β-酮硫酯底物和四种酮还原酶进行了构效关系研究。由于发现与β-酮酰基部分的相互作用最为关键，因此对与该部分接触的残基进行了突变。两个突变就足以完全逆转模型酮还原酶EryKR1的立体选择性，将其从生成(2S,3R)产物的酶转变为生成(2S,3S)产物的酶。
