化学
对映选择合成
酶
生物催化
突变
动力学分辨率
催化作用
组合化学
立体化学
有机化学
生物化学
反应机理
突变
基因
作者
Emina Mehić,Lucija Hok,Qian Wang,Irena Dokli,Marina Svetec Miklenić,Zvjezdana Findrik Blažević,Lixia Tang,Robert Vianello,Maja Majerić Elenkov
标识
DOI:10.1002/adsc.202200342
摘要
Abstract Halohydrin dehalogenases (HHDHs) possess an unnatural activity of introducing functionalities such as N 3 , CN, NO 2 etc., into a molecule through the ring‐opening reaction of epoxides. The enantioselectivity of HHDHs is substrate‐dependent and not always high enough for synthetic applications. B‐group of HHDHs has been neglected in the past, due to observed low enantioselectivity based on performance on a relatively limited number of substrates. Extensive screening of substrates on HheB2 from Mycobacterium sp. GP1 and HheB from Corynebacterium sp. N‐1074 was performed. Several highly enantioselective reactions were discovered ( E >200), with HheB showing higher enantioselectivity and activity toward larger panel of substrates compared to HheB2. Enzymes HheB and HheB2 are highly homologous; they differ by only 4 residues. By using site‐directed mutagenesis, residues 120 and 125 were found to be responsible for higher enantioselectivity of HheB compared to HheB2. Computational analysis supported experiments and provided evidence that kinetic and thermodynamic parameters of reactions within HheB enzymes are crucial in determining the observed enantioselectivities. Due to remarkable activity and enantioselectivity, B‐group HHDHs emerged as a catalyst of choice for the synthesis of bulky tertiary alcohols, as shown in this work. magnified image
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