An article Engineering an alcohol dehydrogenase with enhanced activity and stereoselectivity toward diaryl ketones: reduction of steric hindrance and change of the stereocontrol element WOS:000526708900006 published article about CARBONYL REDUCTASE; INSIGHTS; PROLINE; MUTAGENESIS; CATALYSIS; DYNAMICS; PRELOG; POCKET; OXIDE; SHAPE in [Wu, Kai; Yang, Zhijun; Meng, Xiangguo; Chen, Rong; Huang, Jiankun] Shanghai Univ Med & Hlth Sci, Sch Pharm, 279 Zhouzhu Highway,Pudong New Area, Shanghai 201318, Peoples R China; [Wu, Kai; Yang, Zhijun; Meng, Xiangguo; Shao, Lei] Shanghai Univ Med & Hlth Sci, Microbial Pharmacol Lab, 279 Zhouzhu Highway,Pudong New Area, Shanghai 201318, Peoples R China; [Shao, Lei] Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 285 Gebaini Rd, Shanghai 200040, Peoples R China in 2020.0, Cited 44.0. The Name is Phenyl(pyridin-2-yl)methanone. Through research, I have a further understanding and discovery of 91-02-1. Recommanded Product: Phenyl(pyridin-2-yl)methanone
Steric hindrance in the binding pocket of an alcohol dehydrogenase (ADH) has a great impact on its activity and stereoselectivity simultaneously. Due to the subtle structural difference between two bulky phenyl substituents, the asymmetric synthesis of diaryl alcohols by bioreduction of diaryl ketones is often hindered by the low activity and stereoselectivity of ADHs. To engineer an ADH with practical properties and to investigate the molecular mechanism behind the asymmetric biocatalysis of diaryl ketones, we engineered an ADH from Lactobacillus kefiri (LkADH) to asymmetrically catalyse the reduction of 4-chlorodiphenylketones (CPPK), which are not catalysed by the wild type (WT) enzyme. Mutants seq1-seq5 with gradually increased activity and stereoselectivity were obtained through iterative shrinking mutagenesis. The final mutant seq5 (Y190P/I144V/L199V/E145C/M206F) demonstrated the highest activity and excellent stereoselectivity of >99% ee. Molecular simulation analyses revealed that mutations may enhance the activity by eliminating steric hindrance, inducing a more open binding loop and constructing more noncovalent interactions. The pro-R pose of CPPK with a halogen bond formed a pre-reaction conformation more easily than the pro-S pose, resulting in the high ee of (R)-CPPO in seq5. Moreover, different halogen bonds formed due to the different positions of chlorine substituents, resulting in opposite substrate binding orientation and stereoselectivity. Therefore, the stereoselectivity of seq5 was inverted toward ortho- rather than para-chlorine substituted ketones. These results indicate that the stereocontrol element of LkADH was changed to recognise diaryl ketones after steric hindrance was eliminated. This study provides novel insights into the role of steric hindrance and noncovalent bonds in the determination of the activity and stereoselectivity of enzymes, and presents an approach producing key intermediates of chiral drugs with practical potential.
Recommanded Product: Phenyl(pyridin-2-yl)methanone. Welcome to talk about 91-02-1, If you have any questions, you can contact Wu, K; Yang, ZJ; Meng, XG; Chen, R; Huang, JK; Shao, L or send Email.
Reference:
Pyridine – Wikipedia,
,Pyridine | C5H5N – PubChem